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Dissertations / Theses on the topic 'Drugs administration'
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1
Weise-Kelly, Lorraine Ann. "Drug-induced ataxia : effect of the self-administration contingency /." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0030/NQ66245.pdf.
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2
Cai, Bing. "Ceramic Materials for Administration of Potent Drugs." Doctoral thesis, Uppsala universitet, Tillämpad materialvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-245031.
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This thesis aimed to investigate and document the potential of applying ceramics in two specific drug delivery applications: tamper-resistant opioid formulations and transdermal enhancement protrusions. Geopolymers were developed into the matrix for a tamper-resistant formulation, aiming to protect drug substances from non-medical abuse. The synthesis conditions and excipients composition of the geopolymer-based formulation were modified in this work to facilitate a stable and extended drug delivery. Results showed that 37ºC 100% humidity for 48 hours were applicable conditions to obtain geopolymer with suitable mechanical strength and porosity. Moreover, it was found that the integration of poly(methyl acrylate) into the geopolymer-based formulation could reduce the drug release at low pH and, meanwhile, maintain the mechanical strength. Therefore, the geopolymer-based drug formulations concluded from these studies were applied in oral and transdermal delivery systems. Evidence of the tamper-resistance of geopolymer-based oral and transdermal formulations was documented and compared to the corresponding commercial opioid formulations. The results provided experimental support for the positive effects of geopolymers as drug carriers for the tamper-resistance of oral and transdermal delivery systems. Self-setting bioceramics, calcium phosphate and calcium sulfate were fabricated into transdermal enhancement protrusions in this work for the first time. Results showed that, under mild conditions, both bioceramics could form pyramid-shaped needles in the micron size. The drug release from these needles could be controlled by the bulk surface area, porosity and degradation of the bioceramics. An in vitro insertion test showed that the bioceramic microneedles had enough mechanical strength to insert into skin. Further optimization on the geometry of needles and the substrate material was also performed. The higher aspect-ratio needles with a flexible and self-swellable substrate could release most of the drug content within 4 hours and could penetrate through the stratum corneum by manual insertion. This study explored the potential application of bioceramics in transdermal enhancement protrusions and showed promising indication of their future developments.
3
Copping, N. M. "Studies on the rectal administration of drugs." Thesis, University of Nottingham, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372664.
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Espefält, Westin Ulrika. "Olfactory Transfer of Analgesic Drugs After Nasal Administration." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7829.
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Nasal administration of analgesics for achieving rapid pain relief is currently a topic of great interest. The blood-brain barrier (BBB) restricts access to the central nervous system (CNS) for several central-acting drugs, such as morphine and dihydroergotamine, which results in a substantial effect delay. Evidence for the olfactory transfer of drugs from the nasal cavity to the CNS after nasal administration, bypassing the BBB, is available for both animals and humans. The aims of this thesis were to study the olfactory transfer of morphine to the CNS after nasal administration, and to compare the nasal transport of analgesic drugs across nasal respiratory and olfactory mucosa. In vivo studies in rodents demonstrated that morphine is transferred via olfactory pathways to the olfactory bulbs and the longitudinal fissure of the brain after nasal administration. Further, olfactory transfer of morphine significantly contributed to the early high morphine brain hemisphere concentrations seen after nasal administration to rats. Olfactory transfer was tracked by collecting and analysing brain tissue and blood samples after right-sided nasal administration and comparing the results to the situation after i.v. administration. The olfactory transfer was also visualised by brain autoradiography. In vitro studies indicated that the olfactory mucosa should not be a major barrier to the olfactory transfer of dihydroergotamine or morphine, since transport of these drugs was no more restricted across the olfactory mucosa than across the nasal respiratory mucosa. The in vitro studies were performed using the horizontal Ussing chamber method. This method was further developed to enable comparison of drug transport across nasal respiratory and olfactory mucosa which cannot be achieved in vivo. In conclusion, these analgesic drugs showed potential for olfactory transfer, and access to the CNS by this route should be further investigated in humans, especially for the drugs with central effects that are currently under development for nasal administration.
5
Espefält, Westin Ulrika. "Olfactory transfer of analgesic drugs after nasal administration /." Uppsala : Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7829.
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Lukashevych, I. V. "Efficacy of some herbal drugs administration for patients with urolithiasis." Thesis, БДМУ, 2017. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/17098.
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Popova, M. "The risk of avitaminosis due to administration of antivitamin drugs." Thesis, Київський національний університет технологій та дизайну, 2019. https://er.knutd.edu.ua/handle/123456789/14395.
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Mauludin, Rachmat [Verfasser]. "Nanosuspensions of poorly soluble drugs for oral administration / Rachmat Mauludin." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/102346568X/34.
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Hu, Leijun. "Suramin pharmacokinetics after regional or systemic administration." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1114449390.
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Falcone, Pin Bruno Nicolás. "Physicochemical properties of inhalation drugs." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648175.
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Sorensen, Lene. "Implementation of medication reviews and use of dose administration aids for patients at risk of medication misadventure /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16806.pdf.
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Benjamin, Daniel E. (Daniel Ernest). "The effects of sustained gepirone administration on rodent brain 5-HT receptors and behavioral analogues of anxiety." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc798440/.
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Clinical evidence has demonstrated that the anxiolytic effects produced by the selective 5-hydroxytryptamine1A (5-HT1A) receptor agonist, gepirone, increase progressively over one to three weeks of treatment.
13
Wong, Ka Yeung Mark. "Drug clearance mechanisms and chemotherapy response." Thesis, The University of Sydney, 2007. https://hdl.handle.net/2123/28094.
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Cytotoxic chemotherapeutic agents have a major role in the treatment of cancers. However, many cytotoxic agents have a narrow therapeutic window with best treatment response achieved only within a small range of drug concentrations.
14
Gersper, Beth E. "NETWORK ANALYSIS OF DRUGS OF ABUSE IN OHIO AND POLICY IMPLICATIONS." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron156761393419992.
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Warne, Rhonda J. "Trends in the use of psychotropic medication in residential aged care facilities prior to and after the advent of an accredited pharmacist conducted medication review service." Thesis, The University of Sydney, 2001. https://hdl.handle.net/2123/27725.
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Aim:
To investigate trends in the use of psychotropic medication in
residential aged care facilities prior to and after the advent of an
accredited pharmacist conducted medication review service
(PCMRS).
Objectives:
1. To compare the mean number of psychotropic medications in the
treatment group and comparison group prior to and after the
implementation of a pharmacist conducted medication review
service.
2. To compare the distribution of classes of psychotropic drugs
between the treatment and comparison groups prior to and after a
PCMRS
3. To evaluate the appropriateness of psychotropic medication in
terms of dose, dosing intervals, dose administration and dosing
regimens of benzodiazepines.
Study Design:
A comparative design with repeated measures was used with
residents in the treatment group exposed to a pharmacist conducted
medication review service. For the treatment group data were
collected prior to and after the implementation of this service. For the
comparison group data were collected over corresponding time
periods.
Setting:
A convenience sample of 14 residential aged care facilities in the
Sydney metropolitan area was recruited. The treatment group
consisted of 128 residents randomly selected from 12 residential aged
care facilities serviced by accredited pharmacists. The comparison
sample consisted of all the 121 residents from 2 residential aged care
facilities.
Results:
There was a significant downward trend in psychotropic drug use in
the treatment group. While in the comparison group there was an
increase in psychotropic drug use between the two time periods (p
<0.001). There were no differences in the distribution of psychotropic
drug classes between the treatment and comparison groups overtime.
A trend towards improvement in the overall appropriateness of a
resident's psychotropic medication regimen in the treatment group
was also observed overtime (p= 0.13). Fifty percent of the
pharmacist's recommendations in the treatment group adopted by the
general practitioner related to achieving a more appropriate use of the
medication and 40% to ceasing a drug.
Conclusion:
This research provides preliminary evidence of a reduction of
psychotropic drug use in residential aged care facilities following a
pharmacist conducted medication review service. The concomitant
improvement in the overall appropriateness of use adds credence to a
positive contribution of the pharmacist to the quality use of
psychotropic medication.
16
Sullivan, Donald L. "Direct-to-consumer advertising of prescription drugs : measures of effectiveness /." Connect to resource, 1996. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1242751906.
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Bajpai, Sanjay Kumar. "Formulary decision making in health maintenance organizations involving non-steroidal anti-inflammatory drugs /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487777901657504.
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18
Munday, Dale Leslie. "Design, development and evaluation of encapsulated oral controlled release theophylline mini-tablets." Thesis, Rhodes University, 1991. http://hdl.handle.net/10962/d1003255.
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Conventional solid dosage forms often lead to fluctuations which exceed the maximum safe therapeutic level and/or decline below the minimum effective level. It is recognised that many drugs for chronic administration should be administered on a schedule that maintains plasma drug concentration within the therapeutic window. Research in controlled release dosage forms aims at designing a system with a zero-order input (eg, ideally to deliver 8.33% of the dose per hour over a 12 hour duration), producing steady state plasma drug levels. Oral dministration of drugs prepared as a controlled release formulation is extremely popular, and has attracted the attention of pharmaceutical scientists during the last decade. This has been due to the simultaneous convergence of various factors (eg, discovery of novel polymers and devices, better understanding of formulation and physiological constraints, expiration of existing patents, prohibitive cost of developing new drug entities), involved in the development of these delivery systems. Controlled release oral products can be formulated as single or multiple unit dosage forms and the relative merits of multiple unit forms with their own rate controlling systems are well established. This work describes the development of a relatively inexpensive multiple-unit capsule dosage form of theophylline containing coated mini-tablets for drug delivery throughout the gastrointestinal tract. Preformulation studies on theophylline anhydrous included solubility and dissolution rate determinations. Techniques including X-ray powder diffraction, differential scanning colorimetry and infrared spectroscopy provided no evidence of true polymorphism after recrystallisation from various solvents. However, scanning electron micrographs showed the effects of solvent polarity and cooling rate on the size and shape of recrystallised particles. Theophylline granules were manufactured by using various binders and were film coated by fluidised bed technology with various proportions of ethylcellulose, containing varying amounts of PEG 1540. In vitro release rates were dependent upon coating thickness and the proportion of PEG, which, being water soluble, created pores in the coating during dissolution studies as observed by a scanning electron microscope. However, substantial proportions of the drug remained unreleased from the granules. In order to overcome the problems of drug retention, plain granules were used and theophylline mini-tablets (3 mm diameter, weighing 15 - 20 mg) were manufactured and film coated with various Eudragits ® and other polymeric mixtures (soluble and insoluble). In vitro dissolution profiles from samples enclosed in hard gelatin capsules were determined using the USPXXI paddle apparatus in test media at pH 1.2 (HCI), pH 5.4 and 7.4 (phosphate buffers) at 37'C. Monitoring of in vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in < 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasise the usefulness of an animal model for assessment of in vivo drug release and subsequent absorption during the development of modified release dosage forms. Mini-tablets were subjected to isothermal and cyclic stresses to reach conditions for up to 6 months at different temperatures and relative humidity. The film integrity was maintained but ageing of the coating occurred which impeded dissolution. Reduced drug release was temperature related while the effect of relative humidi% was insignific~t. Encapsulated mini-tablets (uncoated and coated with Eudragit RL and RS 2% w/w) equivalent to a 300 mg dose, were evaluated both in vitro and in vivo using beagle dogs. The pharmacokinetic parameters from single and multiple dose studies showed several advantages over Theo-Dur® 300 mg tablets. Precise dosage titration is possible by careful adjustment of the number of encapsulated mini-tablets. This multiple unit mini-tablet delivery system will allow for greater flexibility in dosage adjustment compared to the currently available preparations, allowing individualised fine dose titration in those patients requiring therapeutic drug monitoring. The developmentof the multiple unit mini-tablet formulation appears to provide an optimal dosage form with maximum flexibility in respect of dose, duration range and ease of production.
19
Bellebaum, Katherine Louise. "The relationship between nurses' work hours, fatigue, and occurrence of medication administration errors." Columbus, Ohio : Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1222114579.
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Chrisinger, Laura. "Policies and practices associated with medication administration in Ohio public elementary schools." Connect to this title online, 2004. http://hdl.handle.net/1811/180.
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Thesis (Honors)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains 24 p.; also includes graphics (some col.). Available online via Ohio State University's Knowledge Bank. Includes bibliographical references (p. 20-21). Available online via Ohio State University's Knowledge Bank.
21
Hansen, Tue. "Spray-dried o/w-emulsions for oral delivery of poorly soluble drugs /." Cph. : The Danish University of Pharmaceutical Sciences, Department of Pharmaceutics, 2004. http://www.dfh.dk/phd/defences/tuehansen.htm.
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22
Patel, Fathima. "The development and assessment of a generic carbamazepine sustained release dosage form." Thesis, Rhodes University, 2006. http://eprints.ru.ac.za/1339/.
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23
Heard, Sharon D. "Evaluation of Bureau Practice for Illegal Drugs Use Among Teens." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1126.
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The Bureau of Substance Abuse Treatment Recovery and Prevention, which oversees drug intervention services for Detroit residents, has found the city's illegal drug use among teens to mirror national rates. Illegal drug use is associated with addiction, major health problems, and stigma. Incorporating evidence-based screening during all teen health care visits would decrease missed opportunities to identify at-risk behaviors, the number of teens that do not receive intervention, and the stigma associated with screening. The purpose of this project was to develop evidence-based policy and practice guidelines for teen screening services for illegal drug use. The Plan-Do-Study-Act (PDSA) model was used to guide the project. An interdisciplinary team of direct service and administrative staff selected questions based on 6 key words---car, relax, alone, forget, friends, and trouble (CRAFFT)---to screen teens for illegal drug use. The interdisciplinary team also developed a teen screening policy along with practice guidelines for the screening policy, implementation plan, and project evaluation. A review of the literature provided support for the project methods. Two experts in the field of substance abuse provided content validity for the policy and practice guidelines, and concluded that the CRAFFT screening questions were valid for evidence-based screening for illegal drug use among teens, that the PDSA model was effective to guide the project, and that an interdisciplinary team approach was effective to address the issue. These findings may improve identification of at-risk teens, decrease missed screening opportunities, decrease stigma, and align the Bureau with current trends in substance abuse treatment.
24
Cabrera, Brooke A. "The impact of direct-to-consumer (DTC) prescription drug advertising on the pharmaceutical salesperson/doctor relationship : a pilot study." Honors in the Major Thesis, University of Central Florida, 2003. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/310.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.Bachelors
Business Administration
Marketing
25
Fütterer, Sören [Verfasser]. "Nanoparticular iron complex drugs for parenteral administration - physicochemical characterization, biological distribution and pharmacological safety / Sören Fütterer." Mainz : Universitätsbibliothek Mainz, 2014. http://d-nb.info/1054682879/34.
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Öhman, Daniel. "Bioanalytical development for application in therapeutic drug monitoring : focus on drugs used in psychiatry /." Linköping : Univ, 2003. http://www.bibl.liu.se/liupubl/disp/disp2003/med775s.pdf.
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Komperlla, Mahesh Kumar. "The formulation and evaluation of rapid release tablets manufactured from Artemisia Afra plant material." Thesis, University of the Western Cape, 2004. http://etd.uwc.ac.za/index.php?module=etd&.
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Infusions, decoctions, alcoholic preparations and other dosage forms of Artemisia afra are frequently used in South African traditional medicine. Generally when these preparations are made without applying good manufacturing practices they do not meet microbial quality control standards, safety and toxicity criteria and encourage poor patients compliance. To overcome the aforementioned disadvantages of traditional dosage forms a sold dosage form, i.e. a table might be recommended. The first objective of this study was to formulate and manufacture a rapid release tablet dosage of Artemisia afra that would contain an amount of plant material equivalent to that found in its traditional liquid dosage forms and that would meet conventional pharmaceutical standards. The second objective was to conduct a pilot study to obtain a preliminary profile of the bioavailability of select flavonoids presents in both the tablet and traditional liquid preparation of Artemisia afra in humans.
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Turner, Gordon Neil. "Organisational climate and standards of nursing care : the administration of depot neuroleptic drugs to psychiatric out-patients." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/21576.
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The findings showed that nurses placed the greatest emphasis on issues related to drug injection techniques while the wider concerns of long term depot medication therapy, including monitoring drug side-effects and assessing general health and social well-being, were generally given a lower priority. Significant differences existed between the four Managerial Sectors of the main study area in terms of both the standards of nursing care observed and the Organisational Climates reported by nurses. The highest standards of care were found to exist in a Managerial Sector where nurses dealt with significantly smaller numbers of patients and where they had access to more comprehensive information. The relationship between Climate and standards of care was also found to be significant. Where there was a greater emphasis on innovation, standards of nursing care, and aspects of organisational structure, higher standards of nursing care were observed. The findings reveal important practical and theoretical concerns pertinent to the different standards of nursing care observed. The findings suggest that certain organisational characteristics appear to facilitate the delivery of a higher standard of nursing care. The utility of adopting an organisational approach in exploring nursing care issues is discussed. Recommendations for changes to the existing arrangements for depot drug administration within the study area are suggested.
29
Howerton, Franklin Ray. "Veteran dedication makes them more efficient in receiving directions on medication, driving veterans to be more medication compliant." CSUSB ScholarWorks, 2001. https://scholarworks.lib.csusb.edu/etd-project/1749.
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The purpose of this study was to determine if there is a relationship between having military discipline, the military rank, the branch of service, the number of years served, reserve status and if these factors would affect a veterans' compliancy in taking daily medication.
30
Breitsamer, Michaela [Verfasser], and Gerhard [Akademischer Betreuer] Winter. "Lipid-based depots : manufacturing, administration and interactions of protein drugs with lipid formulations / Michaela Breitsamer ; Betreuer: Gerhard Winter." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1193049105/34.
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Sadideen, Faddy. "An investigation of changes in NMDA-receptor evoked monoamine efflux following administration of antidepressant drugs : a microdialysis study." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404595.
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Bredenberg, Susanne. "New Concepts in Administration of Drugs in Tablet Form : Formulation and Evaluation of a Sublingual Tablet for Rapid Absorption, and Presentation of an Individualised Dose Administration System." Doctoral thesis, Uppsala University, Department of Pharmacy, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3433.
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This thesis presents two new concepts in oral drug administration and the results of evaluation of some relevant formulation factors.
Investigation into improving the homogeneity of mixtures for tableting indicated that it may be possible to obtain interactive dry mixtures of micronised drugs containing drug proportions as low as 0.015% w/w. By studying the relationship between disintegration time and tensile strength, it was found that the microstructure surrounding the disintegrant particles may influence the disintegration process. Therefore, avoidance of excipients which are highly deformable or very soluble in water will result in more rapid disintegration. Further, it is possible to increase the bioadhesive properties of a non-bioadhesive carrier material by forming interactive mixtures containing a fine particulate bioadhesive material.
The new sublingual tablet concept presented is based on interactive mixtures consisting of a water-soluble carrier covered with fine drug particles and a bioadhesive component. With this approach, it is possible to obtain rapid dissolution in combination with bioadhesive retention of the drug in the oral cavity. Clinical data indicate that this allows rapid sublingual absorption while simultaneously avoiding intestinal absorption.
An individualised dose administration system is also presented. This system is based on the use of standardised units (microtablets), each containing a sub-therapeutic amount of the active ingredient. The required dose is fine-tuned by electronically counting out a specific number of these units using an automatic dose dispenser. A patient handling study supported the suggestion that the dosage of some medications can be more easily and safely individualised for each patient with this method than by using traditional methods of mixing different standard tablet strengths or dividing tablets.
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Sachikonye, Tinotenda Chipo Victoria. "Development and assessment of minocycline sustained release capsule formulations." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1013127.
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The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.
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Khamanga, Sandile Maswazi Malungelo. "Formulation and assessment of verapamil sustained release tablets." Thesis, Rhodes University, 2005. http://hdl.handle.net/10962/d1018236.
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The oral route of drug administration is most extensively used due to the obvious ease of administration. Verapamil hydrochloride is a WHO listed phenylalkylarnine, L-type calcium channel antagonist that is mainly indicated for cardiovascular disorders such as angina pectoris, supraventricular tachycardia and hypertension. Due to its relatively short half-life of approximately 4.0 hours, the formulation of a sustained-release dosage form is useful to improve patient compliance and to achieve predictable and optimized therapeutic plasma concentrations. Direct compression and wet granulation were initially used as methods for tablet manufacture. The direct compression method of manufacture produced tablets that exhibited formulation and manufacturing difficulties. Mini-tablets containing veraparnil hydrochloride were then prepared by wet granulation using Surelease® E-7-19010.and Eudragit® NE 30D as the granulating agents after which the granules were incorporated with an hydrophilic matrix material, Carbopol® 974P NF. Granule and powder blends were evaluated using the angle of repose, loose and tapped bulk density, Can's compressibility index, Hausner's ratio and drug content. Granules with good flow properties and satisfactory compressibility were used for further studies. Tablets were subjected to thickness, diameter and weight variation tests, crushing strength, tensile strength, friability and content uniformity studies. Tablets that showed acceptable pharmaco-technical properties were selected for further analysis. Drug content uniformity and dissolution release rates were determined using a validated isocratic HPLC method. Initially, USP apparatus 1 and 3 dissolution apparatus were used to determine in-vitro drug release rates from the formulations over a 22-hour period. USP apparatus 3 was finally selected as it offers the advantages of mimicking, in part, the changes in the physicochemical environment experienced by products in the gastro-intestinal tract. Differences in release rates between the test formulations and a commercially available product, Isoptin® SR were observed at different pH's using USP apparatus 1. The release of veraparnil hydrochloride from matrix tablets was pH dependent and was markedly reduced at higher pH values. This may be due, in part, to the poor solubility of veraparnil hydrochloride at these pH values and also the possible interaction of verapamil hydrochloride with anionic polymers used in these formulations. Swelling and erosion behaviour of the tablets were evaluated and differences in behaviour were observed which may be attributed to the physico-chemical characteristics of the polymers used in this study. In-vitro dissolution profiles were characterized by the difference (j1) and similarity factor (j2) and also by a new similarity factor, Sct. In addition, the mechanism of drug release from these dosage forms was mainly evaluated using the Korsmeyer-Peppas model and the kinetics of drug release assessed using other models, including Zero order, First order, Higuchi, HixsonCrowell, Weibull and the Baker-Lonsdale model. Dissolution kinetics were best described by application of the Weibull model, and the Korsmeyer-Peppas model. The release exponent, n, confirmed that drug release from these dosage forms was due to the mixed effects of diffusion and swelling and therefore, anomalous release kinetics are predominant. In conclusion, two test batches were found to be comparable to the reference product Isoptin® SR with respect to their in-vitro release profiles.
35
Reich, Heather M. "Medication management among Medicare eligible Ball State retirees." Virtual Press, 2008. http://liblink.bsu.edu/uhtbin/catkey/1399188.
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This study investigated the personal medication management practices of some Medicare eligible university retirees and their dependents. This is important since older adults often take multiple medications and are more susceptible to adverse reactions and interactions. The general hypothesis regarding where retirees medications are obtained and their understanding of their use was not supported. Responses to the research questions revealed a higher level of understanding and compliance than previously reported by others. Also, they are unlikely to participate in an employer sponsored educational intervention. This may be related to the educational level of the sample. Suggestions for future research including sample selection, questionnaire wording and scaling are discussed.Fisher Institute for Wellness and Gerontology
36
Thomson, William Murray. "Medications, dry mouth and dental caries among older people : a longitudinal study /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09pht4858.pdf.
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Kennedy-Tucker, Patricia Elaine. "Direct-to-Consumer Advertising of Drugs and Patients' Health Care Seeking Behaviors." ScholarWorks, 2014. https://scholarworks.waldenu.edu/dissertations/42.
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Known as direct-to-consumer advertising (DTCA), pharmaceutical companies in the United States are permitted to advertise prescription drugs directly to consumers. The purpose of this quantitative study was to determine if an association exists between DTCA and health care-seeking behaviors. The theoretical framework for this study involved social learning theory, information integration theory, and prospect theory. The research questions identified if exposure to DTCA (a) is associated with physician office visits, (b) influences a patient/physician conversation regarding a prescription, (c) influences requesting a prescription, and (d) has an impact on patients' ratings of the overall interaction with the physician. Data were derived from an online survey adapted from the U.S. Food and Drug Administration. Participants included 235 college-affiliated adults. Data were analyzed using descriptive statistics and analysis of variance. The Bonferroni correction was used to control the family-wise Type I error rate. The most significant findings of this study are that DTCA is associated with patients asking more questions, having more office visits, and patients having a lower overall health status. Future researchers should consider a non-college-affiliated sample and the post-implementation impact of the Affordable Care Act. This study helps to address the community challenges of how DTCA impacts prescription drug use and costs, as well as patients' understanding of the associated risks. Having knowledge of the impact of DTCA can help patients and their communities, employers, and governments make more informed decisions that will positively impact their health, wellbeing, and prescription expenses.
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Kieser, Leith Faye. "Formulation and assessment of monolithic beta blocker sustained release tablets prepared by direct compression." Thesis, Rhodes University, 2002. http://hdl.handle.net/10962/d1003242.
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Beta blockers are commonly prescribed for the chronic treatment of hypertension, one of the most prolific disease states worldwide. The beta blockers selected for this study include acebutolol hydrochloride, labetalol hydrochloride, metoprolol tartrate oxprenolol hydrochloride and propranolol hydrochloride. All of these compounds have a short elimination half-life, necessitating multiple dose per day regimens and therefore the development of sustained release dosage forms incorporating these agents was considered beneficial in terms of extending the dosing interval, with the aim of improving patient compliance and subsequent therapeutic outcomes. Preformulation studies that were conducted included moisture content analysis by Karl Fischer titration, and DSC, a method used to predict potential interactions between the drugs and tablet excipients. Tablets were manufactured by both wet granulation and direct compression techniques, and the resultant drug release characteristics were evaluated using the USP Apparatus 3(BIO.DIS). A validated isocratic HPLC method, capable of separating the five drug candidates simultaneously, was developed and used for the analysis of drug samples. Tablet quality was assessed using analyses that included the physical assessment of weight, diameter, thickness, hardness and friability, as well as content uniformity of tablets, before and after dissolution testing. Direct compression tablet formulations containing each of the five beta blockers were successfully adapted from a prototype wet granulation matrix tablet containing metoprolol tartrate, and various formulation variables were investigated to establish,their effect on the rate and extent of drug release from these tablets. The grade and quantity of ethylcellulose used in the wet granulation and direct compression formulae influenced the release rate of some drug candidates. In addition, an alternative formulation method, involving freeze-drying of the drug with an ethylcellulose dispersion, was shown to have potential for altering release rates further. Anti-frictional agents, talc and colloidal silicon dioxide, did not affect drug release from these matrices,however, they affected the physical character:istics such as tablet weight and thickness, of the resultant tablets. All of the matrix tablets formulated were shown to release drug according to square root of time kinetics, in a sustained manner over a 22 hour period.
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Chu, Leonard Yi. "Dissolving microneedles for cutaneous drug and vaccine delivery." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/37177.
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Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues.
Microneedles are micron-size needles that deliver drugs or biopharmaceuticals into skin by creating tiny channels in the skin. This thesis focuses on dissolving microneedles in which the needle tips dissolve and release the encapsulated drug or vaccine upon insertion. The project aimed to (i) design and optimize dissolving microneedles for efficient drug and vaccine delivery to the skin, (ii) maintain vaccine stability over long-term storage, and (iii) immunize animals using vaccine encapsulated microneedles. The results showed that influenza vaccine encapsulated in microneedles was more thermally stable than unprocessed vaccine solution over prolonged periods of storage time. In addition, mice immunized with microneedles containing influenza vaccine offered full protection against lethal influenza virus infection.
As a result, we envision the newly developed dissolving microneedle system can be a safe, patient compliant, easy to-use and self-administered method for rapid drug and vaccine delivery to the skin.
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Sari, Peyami, and n/a. "Isotropic medium chain mono- and diglyceride systems : vehicles for subcutaneous injection in sheep." University of Otago. School of Pharmacy, 2005. http://adt.otago.ac.nz./public/adt-NZDU20070405.160443.
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Purpose: To develop an approach to formulating an injectable solution containing both hydrophilic and lipophilic drugs for subcutaneous administration. Based on the literature survey, isotropic medium chain mono-and diglyceride (MCMDG) systems were chosen for study. For this purpose, analytical methods were developed and validated. In vitro assessments of the MCMDG systems, and in vitro release and in vivo studies were conducted.
Methods: The phase diagrams of the isotropic MCMDG systems were constructed with systems comprising two and three components. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. The validated HPLC assay methods were developed for determination of levamisole and abamectin in liquid formulations and in sheep plasma. The HPLC assay was capable of evaluating stability of abamectin and levamisole in liquid formulations. Solubilities of levamisole hydrochloride or levamisole phosphate and abamectin were determined in the isotropic MCMDG formulations using a HPLC assay method. Stabilities of levamisole phosphate and abamectin were conducted in the isotropic MCMDG formulations at 60�C for 10 days. In vitro release studies for levamisole phosphate were carried out for selected formulations using modified Franz diffusion cells. Based on stability and in vitro release studies, one formulation (MCMDG/propylene glycol (PG):glycerol formal (GF), 20/20:60 % w/w) was selected for a preliminary in vivo study. The selected MCMDG/PG:GF (20/20:60) formulation containing both levamisole phosphate and abamectin was injected subcutaneously into sheep, and the injection site was examined after subcutaneous injection. Pharmacokinetic profiles were determined. A correlation between in vitro fraction released (FR) and in vivo fraction absorbed (FA) for levamisole phosphate from the MCMDG/PG:GF (20/20:60) formulation was assessed.
Results: The isotropic systems of the MCMDG systems containing two or three components were characterized through phase diagrams and viscosity. The solubility of the levamisole hydrochloride in the isotropic MCMDG/sesame oil/water formulations was higher in the absence of abamectin than in combination with abamectin. Solubility of levamisole phosphate was higher in the MCMDG system containing GF or PG compared to the MCMDG/SO/water system. The isotropic MCMDG/PG:GF systems allowed preparations of levamisole phosphate/abamectin solution dose forms containing more than the usual dosage of levamisole. Stability of both levamisole phosphate and abamectin in MCMDG/PG:GF formulations was higher compared with MCMDG/PG:GF/water formulations. Levamisole phosphate degraded in the presence or absence of abamectin in the MCMDG/PG:GF (20/20:60) formulation at 60�C for 10 days. Abamectin alone was found to be stable in the formulation at 60�C for 10 days. In vitro release of levamisole phosphate from water and the MCMDG formulations tested displayed first-order kinetics. Water from the receptor compartment was observed to pass through the membrane into the donor compartment. Therefore, an advancing layer of turbidity occurred in the donor phase. A highly significant decrease in release rate of levamisole phosphate was obtained in MCMDG/GP:GF (20/20:60) formulation compared to water and the other formulations. Pharmacokinetic studies of subcutaneous injection of MCMDG/PG:GF 20/20:60) formulation showed the tmax values of 2.2 h and 4.2 days for levamisole phosphate and abamectin, respectively. The Cmax was 0.94 [mu]g/ml for levamisole phosphate and 6.24 ng/ml for abamectin while the formulation displayed the AUC value was 5.2 [mu]g�h�ml⁻1 for levamisole phosphate and 84.7 ng�day�ml⁻1 for abamectin. No inflammatory reaction was observed at the injection site. Linear regression analysis showed that a significant relationship between the FR (in vitro) and FA for the subcutaneously injected formulation.
Conclusion: The study carried out in this thesis introduces a new approach to formulating an injectable solution of the isotropic MCMDG/PG:GF systems containing both levamisole (hydrophilic drug) and abamectin (lipophilic drug) for subcutaneous administration, and presents the development of the HPLC assay methods for determination of levamisole and abamectin in liquid MCMDG formulations and plasma, in order to investigate in vitro and in vivo release from the isotropic MCMDG/PG:GF formulations. The MCMDG/PG:GF formulations may represent an alternative to the more traditional formulations for both lipophilic and hydrophilic drugs.
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Eduardo, Da Silva Acarilia. "Nanotechnological delivery systems for the oral administration of active molecules : Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00856598.
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This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S-100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spray-dried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on medium-chain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophilic-lipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 µg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB.
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Silva, Acarilia Eduardo da. "Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13309.
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This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit? S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB
Esta tese teve como objetivo o desenvolvimento de novos sistemas de libera??o para duas mol?culas distintas. Na primeira parte, micropart?culas ? base de xilana e Eudragit? S-100 foram produzidas para encapsular ?cido 5-aminosalic?lico visando ? libera??o c?lonespec?fica. A xilana foi extra?da de sabugos de milho e caracterizada quanto ?s suas propriedades f?sico-qu?micas, reol?gicas e toxicol?gicas. Em seguida, dois m?todos de microencapsula??o foram utilizados: reticula??o interfacial polim?rica e secagem por aspers?o. Os sistemas produzidos foram caracterizados quanto ? morfologia, tamanho m?dio e distribui??o, estabilidade t?rmica, cristalinidade, taxa de encapsula??o e libera??o do f?rmaco in vitro. Foram obtidas micropart?culas com adequadas caracter?sticas f?sicas e rendimentos satisfat?rios atrav?s dos dois m?todos, embora os sistemas aspergidos tenham apresentado maior estabilidade t?rmica e sejam considerados mais interessantes devido a sua maior estabilidade t?rmica e aus?ncia de agentes t?xicos. No entanto, ajustes precisam ser feitos para melhorar a encapsula??o e libera??o do f?rmaco. Na segunda parte, microemuls?es do tipo ?leo em ?gua (MEs O/A) com base em triglicer?deos de cadeia m?dia (MCT) foram produzidas visando ao carreamento de anfotericina B (AmB) e aumento da sua solubilidade. Foram obtidas MEs O/A sem e com AmB com got?culas em torno de 80 e 120 nm, respectivamente, e ?ndices de polidispers?o de 0,25 e 0,31, respectivamente. A taxa de incorpora??o da AmB foi alta e dependente do volume da fase dispersa. A viabilidade celular n?o foi afetada at? 25 μg/mL da AmB. Portanto, MEs O/A a partir de MCT podem ser promissores sistemas de libera??o para AmB
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Perna, Marla K. "The Effects of Nicotine Administration on Behavior and Markers of Brain Plasticity in a Rodent Model of Psychosis." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etd/1432.
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Schizophrenia affects about 1% of the population. A hallmark of the disorder is increased dopamine D2 receptor sensitivity in the brain. Studies have shown that schizophrenics smoke cigarettes at approximately 4 times the rate of the general population. It has been suggested that nicotine use is a form of self-medication for symptoms in schizophrenia. Smoking behaviors typically begin in adolescence. We assessed effects of nicotine on behavior and brain plasticity in an adolescent rodent model of schizophrenia with the goal of identifying targets for smoking cessation. Methods: Rats were neonatally treated with quinpirole (a D2/D3 agonist) or saline and sensitized to 0.3, 0.5, or 0.7 mg/kg (free base) nicotine or saline, every other day for 9 days, and locomotor activity was recorded. After behavioral testing, animals demonstrating sensitization to 0.5mg/kg nicotine were surgically implanted with a guide cannula, aimed at the nucleus accumbens core. After recovery, animals underwent microdialysis and in vivo samples were collected every 20 minutes for 300 minutes. Postmortem brains from animals exposed to 0.5mg/kg nicotine or saline were dissected and the nucleus accumbens and dorsal striatum were analyzed for brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding protein (pCREB), and glial-cell derived neurotrophic factor (GDNF), all proteins involved in neuronal plasticity. Results: Animals neonatally treated with quinpirole and administered nicotine showed robust increases in locomotor sensitization and a 400% increase in dopamine overflow from the accumbens core, which was greater than all other groups. Nicotine administration led to increased accumbal BDNF levels, which was enhanced by neonatal quinpirole pretreatment. GDNF levels were also increased in control animals given nicotine, which was attenuated to control levels by neonatal quinpirole. Finally, pCREB levels were robustly increased in animals neonatally treated with quinpirole, an effect that was partially attenuated by adolescent nicotine treatment. These data on pCREB suggest a possible biological marker of anhedonia. In conclusion, it is apparent that nicotine results in a robust increase in behavioral activity and changes in neural proteins of brain plasticity that may serve as possible pharmaceutical targets for smoking cessation in schizophrenia.
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Lee, Jeong Woo. "Physical enhancement of transdermal drug delivery: polysaccharide dissolving microneedles and micro thermal skin ablation." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/33920.
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Transdermal drug delivery system has been limited to small and lipophilic drugs because skin has the intrinsic function to protect the body preventing entry of the external species into the body. In this thesis, two physical methods were studied to overcome the skin barrier in the controlled breakage of the skin barrier and to deliver macromolecules-based drugs through the skin; (1) polysaccharide dissolving microneedles and (2) micro thermal skin ablation.
Polysaccharide dissolving microneedles system was designed to break the skin barrier in a minimized size with the mechanically poor material, to release them into skin with the dissolution of microneedles, and to deliver human growth hormone into the living hairless rats. Micro thermal skin ablation was designed to fabricate the device generating the energy impact with the basis of arc discharge, to transfer the energy impact on the skin, to remove stratum corneum selectively with three-dimensionally controlled manner, and to deliver hydrophilic macromolecules through skin.
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Cadete, pires Ana cristina. "Hyaluronic acid nanocapsules for the intracellular delivery of anticancer drugs." Thesis, Angers, 2016. http://www.theses.fr/2016ANGE0071.
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Cette thèse de doctorat avait pour principal objectif le développement d’une méthode viable pour la formulation de nanocapsules d’acide hyaluronique (NCs HA) à des fins d’incorporation et de libération intracellulaire d’agents anticancéreux. La première étape de ce travail a visé le développement d’une méthode d’émulsion spontanée dans laquelle les NCs HA ont été formulées sans avoir recours à des solvants organiques, ni à un travail à haute température ou à un apport énergétique élevé, ce qui fournit des conditions optimales pour l’incorporation de biomolécules sensibles tout en diminuant l’impact environnemental. Un autre avantage de ce système est basé sur l’utilisation d’un dérivé de l’acide hyaluronique modifié hydrophobiquement, ce qui permet la formulation de NCs HA par des interactions hydrophobes, réduisant ainsi la toxicité due à l’addition d’un surfactant cationique. Une fois formulées, les NCs HA étaient caractérisées par une taille de 130 nm et un potentiel zeta négatif de -20 mV. La versatilité de ce nanotransporteur a été confirmée par l’incorporation de différentes molécules : le docétaxel, un agent cytostatique, a été incorporé au sein du coeur huileux, tandis que l’anti-gasdermin B, un anticorps monoclonal, a été piégé au sein de l’enveloppe polymérique. Le taux d’encapsulation du docétaxel était élevé, sa libération contrôlée et sa cytotoxicité maintenue sur la lignée cellulaire A549 de cancer du poumon. Enfin, l’anti-gasdermin B a été associée avec succès à l’enveloppe polymérique de NCs HA et, une fois à l’intérieur de la cellule, l’anti-gasdermin B était capable d’échapper au compartiment endosomal et d’effectivement cibler la protéine intracellulaire gasdermin B, entraînant une importante diminution du comportement migratoire et invasif des cellules de la lignée HCC1954 de cancer du sein. Tous ces résultats mettent en évidence le potentiel de NCs HA auto-émulsifiées en tant que systèmes multifonctionnels pour transporter divers agents anticancéreux, en particulier pour la libération intracellulaire d’anticorps monoclonaux, une approche ambitieuse qui pourrait passer au premier plan parmi les stratégies innovantes dans la lutte contre le cancerThe main goal of this thesis has been the development of hyaluronic acid nanocapsules (HA NCs) as a multifunctional platform for the encapsulation and delivery of diverse anticancer drugs, such as hydrophobic drugs and hydrophilic biomolecules. The first step was the development of a spontaneous emulsification method, where HA NCs were formulated without the need of organic solvents, heat or high energy input, providing conditions for the incorporation of sensitive biomolecules while decreasing the environmental impact. Another advantage of this system is based on the use of a hydrophobically-modified HA derivative that allowed the preparation of HA NCs by hydrophobic interactions rather than electrostatic forces and thus, reducing the toxicity associated to the addition of a cationic surfactant as a counterion. Once formulated, HANCs had a size around 130 nm and a negative zeta potential about -20 mV. Moreover, these nanocapsules were markedly stable under storage conditions and diluted in human plasma, taking forward this system as a potential carrier for intravenous administration. The versatility of this nanocarrier was confirmed by the incorporation of different molecules : docetaxel, a cytostatic drug, was incorporated into the oil core, whereas anti-gasdermin B, a monoclonal antibody, was entrapped into the polymeric shell. Docetaxel was highly encapsulated, released in a sustained manner and its cytotoxicity in A549 lung cancer cell line was maintained. Finally, anti-gasdermin B was successfully associated to the polymeric shell of HA NCs and its intracellular delivery confirmed by confocal microscopy. Once inside the cell, anti-gasdermin B was able to escape the endosomal compartment and to target the intracellular protein gasdermin B, promoting an important decrease in the migratory and invasive behavior of HCC1954 breast cancer cell line. All these results highlight the potential of self-emulsifying HA NCs as multifunctional systems to transport diverse anticancer drugs, with special emphasisin the intracellular delivery of monoclonal antibodies, an ambitious challenge that could open new avenues to fight cancer
En esta tesis se describe el desarrollo de un nuevo método sostenible para la elaboración de nanocápsulas de ácido hialurónico (NCs HA) como una nueva estrategia para el tratamiento del cáncer. Estas nanocápsulas permiten la incorporación de diferentes moléculas terapéuticas, tanto hidrofóbicas como hidrofílicas, y promueven su liberación en el interior de las células tumorales. En primer lugar, se desarrolló un método de autoemulsificación para la preparación de las NCs HA sin el uso de disolventes orgánicos, temperatura o aplicación de energía. Estas condiciones son ideales para la incorporación de biomoléculas lábiles, así como para reducir el impacto medioambiental del proceso. Otra ventaja del sistema reside en el uso de un derivado de HA modificado hidrofóbicamente que permite la formulación de las nanocápsulas sin la adición de un tensoactivo catiónico, reduciendo así la posible toxicidad del sistema. Las NCs HA semantuvieran estables en condiciones de almacenamiento y tras su dilución en plasma, manteniendo un tamaño nanométrico (130 nm) y una carga superficial negativa (-20mV), lo que corrobora su potencial para administración intravenosa. La versatilidad de este nanosistema fue confirmada mediante la incorporación de diferentes moléculas : docetaxel, un fármaco citostático encapsulado en el núcleo oleoso, y anti-gasdermina B, un anticuerpo monoclonal asociado a la cubierta polimérica. El docetaxel fue eficazmente encapsulado, manteniendo su citotoxicidad en la línea celular de cáncer de pulmón A549, mostrando una liberación del sistema de un modo controlado. Finalmente, la anti-gasdermina B fue asociada de manera eficaz a la cubierta poliméricade las NCs HA y su liberación intracelular confirmada por microscopía confocal. Una vezen el interior de la célula, la anti-gasdermina B abandonó el compartimento endosomaly bloqueó de manera efectiva la proteína intracelular gasdermina B, promoviendo así una importante reducción de la migración e invasión de las células HCC1954 de cáncer de mama. Estos resultados ponen de manifiesto el potencial de las NCs HA, preparadas por auto-emulsificación, como sistemas multifuncionales para transportar diversos fármacos, con especial énfasis en la liberación intracelular de anticuerpos monoclonales,una estrategia ambiciosa en la lucha contra el cáncer
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Martí, Coma-Cros Elisabet. "Investigation of branched and linear polymers as oral delivery systems of antimalarial drugs." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667687.
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Malaria is an infectious disease that affects nearly half of the population in 90 countries around the world. In 2017 it was estimated that there were 219 million cases and 435,000 deaths disproportionately distributed worldwide. Indeed, 92 % of malaria cases and 93 % of malaria deaths occur in Africa, while the remaining of the cases are distributed among South East-Asia, Eastern Mediterranean, Western Pacific, and the Americas. Vast global efforts and large economic investments have been made to reduce, control and eliminate malaria, resulting in a great reduction of the incidence in the last two decades. Nevertheless, malaria remains a global public health issue. Actually, malaria in humans is caused by an intracellular protist which has an extremely complicated live cycle that occurs within two hosts, the human and the Anopheles vector. There are five parasite species of the genus Plasmodium capable to infect humans P. ovale, P. malariae, P. knowlesi, P. vivax and P. falciparum, the latter being responsible for the majority of the morbidity and mortality of this disease. Malaria is a treatable disease, however antimalarial drugs must cross at least three sequential membranes (EPM, PVM and PPM) in order to enter the intracellular parasite and reach appropriate therapeutic concentrations; reason why they required drug delivery systems (DDSs). In fact, nano-DDSs have shown to have a positive effect on disease treatment providing solutions to solubility, pharmacokinetics, target selectivity, and/or protection against degradation, resulting in a drug half-life increased. The aim of this thesis was to characterize different polymeric nanocarrier, branched or dendrimeric (DHP-bMPA and HDLDBC-bGMPA) and linear polyamidoamines (PAAs) (AGMA1, ISA1, ISA23 and ARGO7), as oral drug delivery systems. Results obtained performing in vitro experiments demonstrated that PAAs and dendrimers have low unspecific toxicity, no hemolitic activity, specific pRBCs targeting and drug encapsulation capacity. Furthermore, PAAs displayed slow degradation, affinity to parasite proteins, which could explain the preferential binding to pRBCs, and intake by macrophages, indicating PAAs potential to treat other intracellular parasitic disease like Leishmaniasis. Additionally, dendrimers that form spontaneous micellar carrier, and bind to merozoites, showed an intake by HUVEC cells in different location, which could be further investigated to treat as well other disease. On the other hand, encapsulated drugs with the two types of polymers showed optimal in vivo capacity to inhibit Plasmodium growth after i.v or oral administration. Moreover, when PAA-FITC where given to female mosquitoes’ fluorescence was observed in the midgut and in the insect’s tissues. In conclusion, the date showed in this thesis work presented the branched and the linear polymers investigated as a versatile platform for the encapsulation of orally administrated antimalarial drugs, for the direct administration of antimalarial to mosquitoes, and as potential carriers for the treatment of other parasitic diseases.La malària és una malaltia infecciosa que afecta gairebé a la meitat de la població de 90 països d'arreu del món. El 2017 s'estima que va provocar 219 milions de casos i 435.000 morts, el 92% de casos i el 93% de morts es produïren a l'Àfrica. Els darrers anys s'han fet grans esforços globals i inversions econòmiques per reduir, controlar i eliminar la malària, cosa que ha comportat una gran reducció de la incidència en els últims 20 anys. No obstant això, aquesta malaltia continua sent un problema de salut pública global. En humans és causada per un protozou del gènere Plasmodium i concretament se’n coneixen cinc espècies diferents. Però la causant de més morbiditat i mortalitat és P. falciparum. La malaltia en si és tractable, però els fàrmacs antipalúdics han de creuar com a mínim tres barreres seqüencials per tal d'arribar al paràsit a una concentració suficientment elevada. Per això aquests principis actius requereixen sistemes d'administració de fàrmacs que han demostrat tenir efectes positius. L'objectiu d'aquesta tesi ha estat caracteritzar polímers ramificats (DHP-bMPA i HDLDBC-bGMPA) i lineals (AGMA1, ISA1, ISA23 i ARGO7) per l'administració oral d'antipalúdics. Els resultats obtinguts realitzant experiments in vitro i in vivo han demostrat que tots dos tipus de polímers tenen baixa toxicitat inespecífica, no tenen activitat hemolítica, tenen especificitat per pRBCs i bona capacitat d'encapsulació. Els PAAs han demostrat tenir una degradació lenta, afinitat per proteïnes del paràsit, i capacitat per entrar dins de macròfags, una propietat interessant per tractar altres malalties. A més a més els ramificats s'uneixen a merozoites i entren en macròfags. D'altra banda els medicaments encapsulats amb qualsevol dels dos tipus de polímers han mostrat una capacitat òptima in vivo per inhibir el creixement del Plasmodiuim després de l’administració i.v o oral. Per últim, PAAs-FITC administrats a mosquits femelles, s’han pogut observar a l'intestí i altres teixits. Per tant es pot concloure, que les dades recollides en aquesta tesi demostren que tant polímers ramificats com lineals són una plataforma versàtil per a l'encapsulació de medicaments antipalúdics per ser administrat via oral, per a l’administració directa a mosquits, i potencials nanocarriers pel tractament d’altres malalties parasitàries.
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Guiraldello, Rafael Trevisanuto [UNESP]. "Modelo matemático de tratamento de câncer via quimioterapia em ciclos." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/132049.
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000852261.pdf: 1207552 bytes, checksum: 59a74bf7ef7e26862d7f4b690f76982e (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O câncer é uma das principais causas de morte no mundo e afeta uma parcela considerável da população, particularmente em países subdesenvolvidos. De acordo com os dados fornecidos pela Organização Mundial da Saúde (WHO, 2014), 8,2 milhões de pessoas morreram em 2012 devido ao câncer. De acordo com o Instituto Nacional do Cˆancer (Brasil, 2014), a estimativa para o ano de 2014 aponta para a ocorrência de, aproximadamente, 576 mil casos novos de câncer no Brasil. No entanto, muitas destas mortes poderiam ser evitadas. Por exemplo, mais de 30% das mortes poderia ser impedida por um estilo de vida saudável ou por imunização contra infecções que causam câncer (HPV, HBV). Ainda, cânceres detectados precocemente podem ser tratados e curados. Mesmo com câncer em estágio final, o sofrimento dos pacientes pode ser aliviado com um bom cuidado paliativo
The cancer is one of the leading causes of death in the world and affects a considerable portion of the population, particularly in developing countries. According to the World Health Organization (WHO, 2014), 8.2 million people worldwide died from cancer in 2012. In 2014 there are 576 000 new cases of cancer expected in Brazil (Brasil, 2014). Yet, many of these deaths could be avoided. Over 30% of canceres can be prevented by healthy life style or by immunization against cancer causing infections (HBV, HPV). Others can be detected early, treated and cured. Even in the late stage, the suffering of patients can be relieved with good palliative care. In this dissertation, we present a mathematical model with the goal of understanding tumor development and the effect of administration in cycles according two protocols of chemotherapy as well as two methods of drug delivery We begin with an introduction to the biology of cancer taking into account the main aspects for the construction of the mathematical model. Then, a review of the literature for the mathematical model is presented, and then we present a linear stability analysis for the spatially homogeneous model with and without treatment, in order to understand the dynamics of the model. We conclude that the parameters of competition are the main bifurcation parameters of the system, which define the tumor progression and the successful of chemotherapy. With these results and numerical simulations we concluded that the metronomic protocol proves more effective in prolonging the patient's life than the MTD protocol. Moreover, the uniform delivery method along with the metronomic protocol is the most efficient in reducing the density of the tumor during treatment
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Guiraldello, Rafael Trevisanuto. "Modelo matemático de tratamento de câncer via quimioterapia em ciclos /." Botucatu, 2015. http://hdl.handle.net/11449/132049.
Full textAbstract:
Orientador: Paulo Fernando de Arruda ManceraBanca: Marcelo Lobato Martins
Banca: Claudia Helena Pellizzon
Resumo: O câncer é uma das principais causas de morte no mundo e afeta uma parcela considerável da população, particularmente em países subdesenvolvidos. De acordo com os dados fornecidos pela Organização Mundial da Saúde (WHO, 2014), 8,2 milhões de pessoas morreram em 2012 devido ao câncer. De acordo com o Instituto Nacional do Cˆancer (Brasil, 2014), a estimativa para o ano de 2014 aponta para a ocorrência de, aproximadamente, 576 mil casos novos de câncer no Brasil. No entanto, muitas destas mortes poderiam ser evitadas. Por exemplo, mais de 30% das mortes poderia ser impedida por um estilo de vida saudável ou por imunização contra infecções que causam câncer (HPV, HBV). Ainda, cânceres detectados precocemente podem ser tratados e curados. Mesmo com câncer em estágio final, o sofrimento dos pacientes pode ser aliviado com um bom cuidado paliativo
Abstract: The cancer is one of the leading causes of death in the world and affects a considerable portion of the population, particularly in developing countries. According to the World Health Organization (WHO, 2014), 8.2 million people worldwide died from cancer in 2012. In 2014 there are 576 000 new cases of cancer expected in Brazil (Brasil, 2014). Yet, many of these deaths could be avoided. Over 30% of canceres can be prevented by healthy life style or by immunization against cancer causing infections (HBV, HPV). Others can be detected early, treated and cured. Even in the late stage, the suffering of patients can be relieved with good palliative care. In this dissertation, we present a mathematical model with the goal of understanding tumor development and the effect of administration in cycles according two protocols of chemotherapy as well as two methods of drug delivery We begin with an introduction to the biology of cancer taking into account the main aspects for the construction of the mathematical model. Then, a review of the literature for the mathematical model is presented, and then we present a linear stability analysis for the spatially homogeneous model with and without treatment, in order to understand the dynamics of the model. We conclude that the parameters of competition are the main bifurcation parameters of the system, which define the tumor progression and the successful of chemotherapy. With these results and numerical simulations we concluded that the metronomic protocol proves more effective in prolonging the patient's life than the MTD protocol. Moreover, the uniform delivery method along with the metronomic protocol is the most efficient in reducing the density of the tumor during treatment
Mestre
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Popa, Michelle. "An Examination of Awareness of Over-the-Counter Nonsteroidal Anti-Inflammatory Drugs and Adverse Events." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1143.
Full textAbstract:
The elderly population is among the fastest growing populations in the United States. Finding and consuming medications safely and effectively are challenging endeavors for this population. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a widely consumed class of medications among the elderly population, with 70% of individuals consuming over-the-counter (OTC) NSAIDs once a week and 34% using them daily. The purpose of this quantitative study was to determine whether (a) patients are aware of the risks associated with the consumption of NSAIDs, and (b) there are differences in awareness based upon specific demographic characteristics and levels of patient-physician communication. The health belief model (HBM) was used to interpret the results. The HBM is a social cognition framework that takes into account different perceptions, namely, perceived susceptibility of acquiring a health condition, perceived severity of the condition and its consequences, perceived barriers to engaging in the recommended behavior, perceived benefits of engaging in the recommended behavior, and perceived costs of engaging in the recommended behavior. Multiple linear regression was used to analyze the data. The results, which were based upon a cross-sectional survey of 124 participants, showed that the participants' awareness of adverse events associated with NSAIDs use was not associated with sociodemographic variables, rates of consumption, or patient-physician communication. The findings will give the key stakeholders more insight into the issue of preventable adverse events that might lead to the establishment of more safety programs and informatics structural systems to monitor the consumption of OTC NSAIDs and improve lines of communication to protect the elderly population.
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Bretin, Ludovic. "Thérapie photodynamique (PDT) dans un modèle in vitro et in vivo de cancer colorectal : utilisation d'un photosensibilisateur nanovectorisé." Thesis, Limoges, 2019. http://www.theses.fr/2019LIMO0052/document.
Full textAbstract:
Le cancer colorectal (CCR) est l’un des cancers les plus diagnostiqués dans le monde mais surtout le 2ème cancerle plus mortel. Malgré les progrès de la recherche médicale dans les traitements anticancéreux, de nombreux effetssecondaires subsistent chez les patients ainsi que l’apparition de résistances aux traitements conventionnels. Ledéveloppement de nouvelles stratégies thérapeutiques anticancéreuses est donc nécessaire afin d’améliorer la priseen charge de ces patients. La thérapie photodynamique (PDT) utilisant des photosensibilisateurs (PS) se présentecomme une stratégie thérapeutique innovante limitant fortement ces effets secondaires indésirables. La PDT a étéapprouvée pour le traitement de certains cancers grâce à la génération d’espèces réactives de l’oxygènecytotoxiques uniquement après photoactivation des PS. Cependant, une faible solubilité et un manque de sélectivitédes PS vis à vis des sites tumoraux sont les principales limites en clinique. En effet, l’administration ciblée demédicaments est un point essentiel dans la thérapie anticancéreuse. La nanomédecine par l’utilisation denanoparticules permet d’améliorer le ciblage tumoral car elles sont capables de s’accumuler spontanément dansles tumeurs solides grâce à l’effet de perméabilité et de rétention accrue. L’objectif de cette étude a été dedémontrer l’intérêt de la vectorisation de la 5-(4-hydroxyphényl)-10,15,20-triphénylporphyrine-xylane (TPPOHX)sur des nanoparticules de silice (SNPs) afin d’augmenter l’efficacité anticancéreuse par un meilleur ciblagetumoral du traitement. Il a été démontré une augmentation significative de l’efficacité anticancéreuse des TPPOHXSNPs-PDT grâce à l’amélioration de l’internalisation cellulaire par rapport à la TPPOH libre-PDT sur 3 lignéescellulaires de CCR humain. De plus, il a été caractérisé que la mort cellulaire induite par les TPPOH-X SNPs-PDTest dépendante de la voie apoptotique et que l’autophagie joue un rôle de résistance à la mort cellulaire. Par ailleurs,in vivo et en l’absence de toxicité, les TPPOH-X SNPs-PDT induisent une augmentation de l’efficacitéanticancéreuse grâce à un meilleur ciblage tumoral par rapport à la TPPOH libre-PDT. Cette étude a donc permisde démontrer l’intérêt de la combinaison de la PDT et de la nanomédecine afin d’améliorer les futurs traitementsanticancéreuxColorectal cancer (CRC) is one of the most common cancer globally but above all the second leading cause ofdeath for oncological reasons. Despite medical research advances in anti-cancer treatments, many side effectspersist in patients as well as development of resistances to conventional treatments. The development of new anticancertherapeutic strategies is necessary in order to improve care of patients. Photodynamic therapy (PDT) usingphotosensitizers (PS) comes as an innovative therapeutic strategy severely restricting these undesirable sideeffects. PDT has been approved for treatment of some cancers due to the generation of cytotoxic reactive oxygenspecies only with photoactivated PS. However, low physiological solubility and lack of selectivity towards tumorsites are the main limitations of their clinical use. Indeed, targeted drug delivery is a crucial point in cancer therapy.Nanomedicine through the use of nanoparticles improves tumor-targeting because they are able to spontaneouslyaccumulate in solid tumors through an enhanced permeability and retention effect. The purpose of this study wasto prove added value of 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin-xylan (TPPOH-X) vectorization bysilica nanoparticles (SNPs) in order to enhance anti-cancer efficacy through better tumor-targeting. It has beendemonstrated significant anti-cancer efficacy increase of TPPOH-X SNPs-PDT thanks to cellular uptakeimprovement relative to free TPPOH-PDT in 3 human CRC cell lines. Moreover, it has been characterized thatcell death induced by TPPOH-X SNPs-PDT is conducted via apoptosis and autophagy acts as a resistance pathwayto cell death. Furthermore, in vivo and without toxicity, TPPOH-X SNPs-PDT induce an elevated anti-cancerefficacy through improvement of tumor-targeting compared to free TPPOH-PDT. This study therefore highlightedthe added value of PDT and nanomedicine combination in order to improve future cancer treatments