Дисертації: "Theophylline"

1

Awosika, Ajoritsedere. "Biopharmacy of sustained-release theophylline." Thesis, University of Bradford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257819.

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2

Purkiss, Ronald. "Bioequivalence of sustained release theophylline formulations." Thesis, Aston University, 1986. http://publications.aston.ac.uk/12472/.

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The bioequivalence of sustained release theophylline formulations, marketed in the United Kingdom, has been investigated in relation to the co-administration of food in both single dose and steady state volunteer studies. The effect of food on pharmacokinetic parameters and their clinical relevance was researched. Experimentation using drug induced modification of gastric motility to ascertain the component influences of the rate of gastric emptying on the absorption of theophylline from sustained release formulations was conducted. Prolongation of time to maximum plasma theophylline concentration by food reported in the literature and its clinical importance was investigated in once daily compared with twice daily administration of sustained release theophylline formulations and smoking habit. The correlation between saliva and plasma theophylline concentrations as a means of developing a non-invasive sampling techniques was examined. Data obtained from in vitro dissolution studies was compared with in vivo results. This thesis has shown no significant differences occurred in the pharmacokinetic parameters measured between sustained release formulations available in the United Kingdom. The investigations into the influence of food on prolongation of time to maximum plasma theophylline concentration and other measured pharmacokinetic parameters demonstrated no important pharmacokinetic or clinical effects. Smoking adults taking sustained release theophylline formulations had similar drug clearances to those reported in the literature for smokers taking plain uncoated theophylline formulations.

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3

Boer, Jason. "Mechanistic investigation of cytochrome P450 1A2 catalyzed metabolism of 8-alkylxanthines /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/8161.

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4

Zhang, Shuo. "Physical properties and crystallization of theophylline co-crystals." Licentiate thesis, KTH, Transport Phenomena, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-13255.

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This work focuses on the physical properties and crystallization of theophyline co-crystals. Co-crystals of theophylline with oxalic acid, glutaric acid and maleic acid have been investigated.

The DSC curves of these co-crystals show that their first endothermic peaks are all lower than the melting temperature of theophylline. The decomposition temperature of theophylline – oxalic acid co-crystal is at about 230 °C, determined by DSC together with TGA. After decomposition, the remaining theophylline melts at about 279 °C, which is higher than the known melting temperature of theophylline, suggesting a structure difference, ie. a new polymorph may have been formed. The formation of hydrogen bonds in theophylline – oxalic acid co-crystal was investigated by FTIR. Changes of FTIR peaks around 3120 cm^-1 reflects the hydrogen bond of basic N of theophylline and hydroxyl H of oxalic acid. The solubility of theophylline – oxalic acid co-crystal and theophylline – glutaric acid co-crystal was determined in 4:1 chlroform – methanol and in pure chloroform respectively. At equilibrium with the solid theophylline – oxalic acid co-crystal, the theophylline concentration is only 60 % of the corresponding value for the pure solid theophylline. At equilibrium with the solid theophylline – glutaric acid co-crystal, the theophylline concentration is at least 5 times higher than the corresponding value for the pure solid theophylline. Two phases of theophylline were found during the solubility determination. In the chloroform – methanol mixture (4:1 in volume ratio) the solubility of the stable polymorph of theophylline is found to be about 14 % lower than that of the metastable phase. Various aspects of the phase diagram of theophylline – oxalic acid co-crystal was explored.

Theophylline – oxalic acid co-crystal has been successfully prepared via primary nucleation from a stoichiometric solution mixture of the two components in chloroform – methanol mixture. By slurry conversion crystallization, the co-crystal can be prepared in several solvents, and yield and productivity can be significantly increased. Theophylline – glutaric acid can be successfully prepared via both co-grinding of the two components and slow evaporation with seeding.

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5

Chrystyn, H. "Pharmacodynamics of theophylline in irreversible chronic airflow obstruction." Thesis, University of Bradford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379859.

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6

Chen, Chi. "Engineering of inhalation aerosols combining theophylline and budesonide." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/14072.

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In asthma therapy, the use of theophylline to prevent bronchial spasm and glucocorticoids to decrease inflammation is widely indicated. Apart from the acute asthma attack oral theophylline is treated for chronic therapy in order to minimize inflammation and to enhance the efficiency of corticosteroids and recover steroids’ anti-inflammatory actions in COPD treatment. The preferred application route for respiratory disease treatment is by inhalation, such as dry powder inhalers (DPI) being the delivery systems of first choice. As shown recently, there is an advantageous effect if the drugs are given simultaneously which is caused by a synergistic effect at the same target cell in the lung epithelia. Therefore, it seems rational to combine both substances in one particle. This type of particle has the advantage over a combination product containing both drugs in a physical mixture which occurs rather randomly deposition leading to API segregation and non-dose-uniformity. Dry powder inhalers (DPIs) is a type of therapeutic pharmaceutical formulations usually present in the solid form. Due to the nature of the solid-state, an understanding of chemical and physical properties must be established for acquiring optimum performance of the active pharmaceutical ingredients (APIs). In recent year, generation of DPIs is a destructive procedure to meet the micron size. Such processes are inefficient and difficult to control. Moreover, according to current researches on combination APIs formulation, this type of DPIs performed a greater variability in does delivery of each active, leading to poor bioavailability and limit clinical efficient. This result suggest that combination formulations require advanced quality and functionality of particles with suitable physicochemical properties. Hence, in order to production of binary and combination DPIs products, the aim of this study was to develop the spray drying and ultrasonic process for engineering of combination drug particles that will be delivered more efficiently and independently of dose variations to the lung. Microparticles were produced by spray drying or/and ultrasonic technique. The processing parameters and addition of excipients (polymers) were optimized using a full factorial design such that microparticles were produced in a narrow size range suitable for inhalation. Employing excipients resulted in high saturation environment leading to minimized sphere particles when compared to conventional solvent. Solid state characterization of microparticles using powder x-ray diffraction and differential scanning calorimetry indicated that the particles contained crystalline but no cocrystal. The combination particles comparable to or better than micronized drug when formulated as a powder blended with lactose. It was concluded that the use of HPMC enhanced crystallinity suitable for inhalation; and combination particles improved uniform distribution on the stage of NGI.

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7

Haarberg, Hans Eirik. "Theophylline IMAGEtags (intracellular multi aptamer genetic tags) the development and evaluation of an RNA reporter system based on the theophylline aptamer /." [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1464205.

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8

Babey, Anna Marie. "Characterization of the time course of the effects of theophylline administration on adenosine receptors in cultured murine neuroblastoma cells." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28668.

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This thesis examines the effects of continuous theophylline pretreatment on the A$ sb2$ adenosine receptor system in cultured murine neuroblastoma cell lines, which either do or do not also express A$ sb1$ adenosine receptors. N-Ethylcarboxamido adenosine (NECA) stimulates cAMP accumulation and binds to A$ sb2$ receptors in a saturable and biphasic fashion in both types of cell cultures. Sixteen hours of theophylline treatment led to a significant increase in the number of low affinity A$ sb2$ binding sites, as well as a potentiation of NECA-stimulated cAMP accumulation, regardless of whether the cells expressed A$ sb1$ receptors. The enhanced adenylate cyclase stimulation in cells treated for 8 hours is completely blocked by addition of cycloheximide, indicating that new protein synthesis plays a role in the effects of theophylline. The potentiated response to NECA continues through 1 week of treatment in both sets of cultured cells, but disappears after 2 weeks of theophylline pretreatment in the cells expressing both A$ sb1$ and A$ sb2$ receptors. Binding profiles in cells that do not express A$ sb1$ receptors demonstrate that while control cells are sensitive to the effects of the non-hydrolyzable analogue of guanosine triphosphate, Gpp(NH)p, cells that were treated for 4 days or 1 week with theophylline are no longer sensitive to the effects of this compound. This could indicate either an enhanced coupling between the receptor and the stimulatory guanine nucleotide regulatory protein (G$ rm sb{s}$ protein) or a complete uncoupling of these two proteins. There is a significant decrease in the basal cAMP levels after 4 days or more of treatment, as well as an increase in the immunoreactivity of the $ alpha$ subunit of the stimulatory G protein after 2 weeks of treatment. Taken together, these findings would tend to favour the possibility of enhanced coupling between the receptor and the G$ rm sb{s}$ protein. Cells that express both receptor subtypes also show

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9

LABOULAYE, PHILIPPE. "Les intoxications a la theophylline : indications therapeutiques a propos de trois observations." Amiens, 1989. http://www.theses.fr/1989AMIEM017.

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10

Özgarip, Yarkın Bayraktar Oğuz. "Application of Silk Fibroin In Controlled-Release of Theophylline/." [s.l.]: [s.n.], 2004. http://library.iyte.edu.tr/tezler/master/kimyamuh/T000433.pdf.

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11

Dragula, Collen Elizabeth 1964. "A pharmacokinetic study of acrylamide and theophylline in rats." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/276847.

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Effects of age, dosage regimen, dose level, and routes of administration on the pharmacokinetics of acrylamide (ACR) and theophylline (TP) in Fischer 344 rats have been studied. ACR treatment consisted of administration of a single subtoxic dose or of multiple doses known to induce neurotoxicity to 5 and 11 week old rats. The effects of age and dosing regimen on the determination of pharmacokinetic parameters were studied. Multiply dosed rats had significantly longer plasma half lives than the singly dosed animals. Clearance values in the plasma were also significantly decreased following multiple dosing. Animals treated with TP received a single dose at different dose levels either intravenously or orally. No statistical difference was found between beta, Vbeta , and Cl based on dose level. All pharmacokinetic parameters were similar in magnitude to literature values for humans. Following oral dosing, plasma levels of TP were constant for the duration of the experiment. (Abstract shortened with permission of author.)

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12

JOSROLLAND, MONIQUE. "Les dosages de la theophylline dans les milieux biologiques." Strasbourg 1, 1987. http://www.theses.fr/1987STR10728.

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13

Yao, Caiping. "Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYPIA2 and CYP2C19 /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/7967.

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14

Palmer, Derek Adeyemi. "Sensing of theophylline by enzyme immunoassay coupled with electrochemical detection." Thesis, Loughborough University, 1991. https://dspace.lboro.ac.uk/2134/26872.

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The voltammetry of several substrates and their hydrolysis products for the enzyme alkaline phosphatase (E.C. 3.1.3.1.) were investigated and theophylline-alkaline phosphatase (TH-AP) conjugates were synthesized in order to develop a flow injection electrochemical enzyme immunoassay (FIEEIA) for the antiasthmatic therapeutic drug theophylline.

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15

LERAT, JEAN-PAUL. "Recherche d'une interaction pharmacocinetique entre la norfloxacine et la theophylline." Bordeaux 2, 1988. http://www.theses.fr/1988BOR25089.

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16

Chen, Jye-Daa. "Theophylline disposition in patients with hepatic disease and congestive heart failure." Scholarly Commons, 1992. https://scholarlycommons.pacific.edu/uop_etds/2239.

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The theophylline clearance was evaluated in patients with liver dysfunction and/or congestive heart failure. One hundred and twenty two patients were categorized into four groups; Group I: Liver dysfunction (n=20), Group II: Congestive heart failure (CHF, n=22), Group III: Both liver dysfunction and CHF (n=12), and Group IV: Control group (n=68). The severity of liver dysfunction and CHF were evaluated using Child-Turcotte- Pugh index (CTP) and a Cardiac Function index, respectively. Theophylline clearance was significantly decreased in Groups I, II, and III when compared to the control group; but, no significant difference was found among these three groups (mean values were 0.515, 0.479, 0.417, and 0.682 mllmin/kg, respectively). Moreover, patients with compensated cirrhosis or moderate to severe CHF had the lowest theophylline clearance values (mean values 0.344, and 0.335 ml/min/kg, respectively). There was a significant correlation between Cardiac Function index and theophylline clearance (r=-0.621) in Group II. Smokers had larger theophylline clearance values than those of nonsmokers in Groups I, II, and IV. Impairment of theophylline clearance did not correlate well with any of the indices of liver function or the CTP index. A model for prediction of the clearance in CHF was developed, which consisted of a Cardiac Function index and smoking habit. This model accounts for approximately 60% of the variation of theophylline clearance. However, models describing theophylline clearance in liver dysfunction and in congestive heart failure with liver dysfun ction did not appear to be useful. Thus, routine laboratory data and indices of liver function were not helpful in evaluating the impaired hepatic theophylline elimination. The Cardiac Function index appeared to be useful in estimation of theophylline clearance in CHF; however, the association between the theophylline clearance and severe CHF needs to be evaluated further.

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17

Mikhail, May Naim. "Design And Evaluation Of Theophylline Monitoring For Home Health Care Patients." Scholarly Commons, 1987. https://scholarlycommons.pacific.edu/uop_etds/3337.

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The purpose of this study was to design, evaluate, and determine the cost benefit of a pharmacokinetic service for home-based patients. Four randomly selected patient populations were used in evaluating the service for six months. The experimental group consisted of 17 patients who were under the care of family practice physicians in private practice and who received pharmacokinetic consultation and monitoring by a pharmacist as a home health care service. The retrospective control consisted of the same 17 patients of the experimental group whose past medical history for a period of six months was used. The concurrent control consisted of 17 patients who were concurrently treated by the same family practice physicians in private practice who treated the patients in the experimental group. The fourth group consisted of 17 patients who were concurrently treated by family practice physicians in a general hospital outpatient clinic. The service was evaluated by comparing the following variables: serum levels ordered, serum levels ordered inappropriately, physicians' office visits, hospitalizations secondary to pulmonary problems, and emergency room visits secondary to pulmonary problems. A one-way analysis of variance, Scheffe's post hoc test, and t test were used to analyze the results. There was a significant difference (P greater than 0.05) in the number of inappropriate levels ordered, physician's office visits, and emergency room visits. The cost of the service was $134 and the benefit was $218. It was concluded that a homebased pharmacokinetic service is cost beneficial in this patient population.

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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.

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19

Dupont-Duvalet, Géraldine. "Faisabilite de microgranules de 400 mum par extrusion/spheronisation." Lille 2, 1997. http://www.theses.fr/1997LIL2P261.

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20

Ly, Joseph Pang-Hoi. "Development of an oral microspherical formulation for bimodal in vitro release of theophylline." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29336.pdf.

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21

Brophy, Conor Jane. "The effect of theophylline on the respiratory and quadriceps femoris muscles in man /." Title page, contents and abstract only, 1992. http://web4.library.adelaide.edu.au/theses/09MD/09mdb873.pdf.

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22

Scally, C. M. "The effect of theophylline upon the immune response to nasal antigen in man." Thesis, Queen's University Belfast, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261934.

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23

Fritz, Kathleen Gary. "Development of a urinary metabolic ratio that reflects systemic theophylline elimination during pregnancy." Scholarly Commons, 1993. https://scholarlycommons.pacific.edu/uop_etds/2245.

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A number of studies have investigated the natural history of asthma in pregnancy. Most of the data suggests that the course of asthma for a given patient is unpredictable. Turner, et al.7 summarize the data from all of the English-language literature of studies on the effect of pregnancy on astha. Of 1054 cases examined, 49% of the asthma conditions remained unchanged, 22% got worst and 29% became better.7 Theophylline has been used safely during pregnancy. A review of the literature by O'Brien, showed that no teratogenic effects were associated with the use of theophylline in 117 cases and aminophylline in 76 cases examined.39,40 Blood concentration in newborns have been found to be similar to concentrations in the mothers.41,42,43 Problems developed because theophylline clearance may be altered during pregnancy and necessitate dosage adjustments and careful drug level monitoring.44 RATIONALE FOR STUDY Campbell, et al.45 developed a caffeine urinary metabolic ratio, in which they were able to demonstrate a correlation between changes in metabolic rations and clearance. The change in the metabolic ration explained the alteration in clearance and determined the specific Cytochrome P-450 system involved. Various physiologic changes occurring during pregnancy can cause changes in drug disposition. Pharmacokinetic parameters that need to be considered are plasma protein binding capacity, absorption, drug metabolizing enzyme activity, renal excretory function and volume of distribution.44,46,47 This study was developed to determine if changes in theophylline disposition during pregnancy were due to changes in drug metabolizing enzyme activity. A urinary test was designed to investigate the ratios of unchanged theophylline and theophylline metabolites to monitor changes in the various Cytochrome P-450 isoenzyme systems. Changes in the ratios could provide a noninvasive procedure to assess the effect of modulating agents or conditions (such as pregnancy) on theophylline metabolizing enzyme activity.

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24

Buissard, Nathalie. "Ajustement de posologie de la théophylline administrée par voie intra-veineuse à des patients en état de mal asthmatique." Paris 5, 1996. http://www.theses.fr/1996PA05P197.

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25

Oiknine, Michel. "Interactions médicamenteuses de la théophylline." Paris 5, 1988. http://www.theses.fr/1988PA05P144.

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26

BERARD, FLORENCE. "Syndrome de bartter induit : a propos d'un cas." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX20342.

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27

Yahioglu, Fulya. "The development of a fluoroimmunoassay for theophylline using the fluorescence capillary fill device (FCFD)." Thesis, University of Bath, 1995. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307135.

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28

Attia, Sonia. "Amélioration de l'absorption intestinale de la théophylline : utilisation d'une méthode "ex vivo"." Paris 5, 1996. http://www.theses.fr/1996PA05P124.

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29

Buhecha, Mira Dhiraj. "The development and characterization of theophylline and budesonide co-encapsulated poly (lactic acid) (PLA) nanoparticles." Thesis, University of Brighton, 2016. https://research.brighton.ac.uk/en/studentTheses/a46c129a-c404-4132-b7de-1698dc88cdfa.

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Inhaled drug delivery is ideal for treatment of asthma and chronic obstructive pulmonary disease (COPD) as it allows a local action of the medication at the disease site. Biodegradable polymeric nanoparticles which might allow extended/sustained release of inhaled drugs are synthesized using various methods however; these do not permit high encapsulation efficiency for hydrophilic drugs. The aim of the project was to test the hypothesis that it was possible to develop an efficient method for the co-encapsulation of a hydrophilic and lipophilic drug (theophylline and budesonide respectively) into nanoparticles. In order to improve the loading efficiency of both hydrophilic and hydrophobic drugs, a modified double emulsification solvent diffusion (DESD) method was developed and both co-encapsulated and mono-encapsulated nanoparticles (containing either drug) were synthesized. Improved loading efficiency, studied using high performance liquid chromatography (HPLC), for both drugs was obtained. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) showed that particles were in the sub-micron range (150-400 nm). Measurement of zeta potential showed that the particles had a negative surface charge and additionally Fourier-transform infra-red (FT-IR) spectroscopy confirmed that this was due to the polymer and no drug was adsorbed on the external surface of the nanoparticles. Resemblance of nanoparticles thermograms, obtained using differential scanning calorimetry (DSC), to those of the polymer alone suggested successful encapsulation of the drugs. Stability studies of the drug encapsulated nanoparticles conducted at different temperatures indicated that storage conditions of 2-8°C over a period of 6 months showed minimal changes in the particle size, zeta potential and morphological characteristics of the nanoparticles. Storage (of the nanoparticles) at 40°C over the course of 6 months resulted in larger variations on the particle size and zeta potential but also loss of morphological features of the nanoparticles, suggestive of changes in the polymer state at this temperature. Franz diffusion cells were used to study the release of drugs from the nanoparticles over 24 hours at room temperature and at 37oC. The results showed that release of theophylline and budesonide from nanoparticles was biphasic and sustained compared to release of drug from solutions containing an equivalent concentration of drug. The effect of the nanoparticles on the viability of airway epithelial cells was studied using a human bronchial epithelial cell line (16HBE14o-) using a 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The nanoparticles had no significant effect ii on cell viability except at the highest concentration of the suspension studied (5 mg/mL) (P < 0.05). The permeability of 16HBE14o- cells, cultured at an air-liquid interface, to theophylline and budesonide applied in solution and as mono-encapsulated and co-encapsulated nanoparticles was studied. The nanoparticles and drug solutions did not affect the tight junctions of the cells and similar to the results obtained in the Franz diffusion cells, both drugs crossed the cells more slowly when applied as nanoparticles in comparison to the solutions. To study deposition of the nanoparticles; nebulized suspensions of the nanoparticles in de-ionized water and dry powder formulations using different grades of lactose were compared. The prepared formulations were studied using a multi-stage liquid impinger (MSLI). The results indicated that drug deposition was greatest in stages 1 and 2 of the MSLI where particle size was greater than 6.8μm from the dry powder formulations in contrast to deposition throughout the five stages of the MSLI from the nebulized suspension. Morphological assessment of the dry powder formulations using SEM showed nanoparticles adhered to the lactose but also included nanoparticles in the absence of lactose and vice versa. In conclusion, theophylline and budesonide nanoparticles were successfully formulated using PLA by application of the DESD method. Nanoparticles possessed desired physicochemical properties including submicron size range and negatively charged surface; however a higher loading efficiency of the hydrophobic drug was obtained despite modifications to the DESD method. Low toxicity of the nanoparticles to human bronchial epithelial cells and sustained release over a period of 24 hours was achieved. Nanoparticles were delivered successfully in the target site at a desired particle size range when formulated as nebulized suspensions.

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30

Mehta, Bhanvi. "The Formation of Pharmaceutical Co-crystals by Spray Drying. An Investigation into the Chemical and Physical Factors Affecting the Production of Pharmaceutical Co-crystals by Fast Evaporation and Spray Drying." Thesis, University of Bradford, 2016. http://hdl.handle.net/10454/14630.

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Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.

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31

HAKIL, MEHDI. "Degradation de la cafeine par les champignons filamenteux, purification et caracterisation d'une theophylline demethylase d'aspergillus tamarii." Besançon, 1999. http://www.theses.fr/1999BESA2021.

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Les champignons filamenteux sont capables de degrader la cafeine contenue dans la pulpe de cafe ou dans des milieux entierement synthetiques. Les enzymes impliquees dans cette degradation n'ont jamais ete caracterisees a l'etat pur chez les champignons filamenteux. Notre objectif etait de purifier une enzyme impliquee dans la degradation de la cafeine afin de la caracteriser. Sur 20 souches de champignons filamenteux testees, 3 aspergillus et 4 penicillium commune ont ete capables de degrader la cafeine d'un milieu liquide ne contenant pas d'autre source d'azote. Ces 7 souches degradent la cafeine en theophylline, puis en 3-methylxanthine par des reactions de demethylation successives. Elles sont aussi capables d'utiliser la theophylline, la theobromine et la paraxanthine comme seule source d'azote. Une des souches les plus performantes, aspergillus tamarii, a ete cultivee sur 2 supports solides impregnes d'une solution nutritive. Pour les deux types de supports solides utilises les produits de degradation obtenus sont la theophylline et la 3-methylxanthine. L'ajout de sources simples d'azote (sulfate d'ammonium, uree) aux milieux de culture, inhibe la degradation de la cafeine qui debute lorsque les sources simples d'azote sont epuisees et si la source de carbone est toujours disponible dans le milieu de culture. Les activites cafeine et theophylline demethylases ont ete comparees in vitro dans un extrait brut cytoplasmique d'a. Tamarii obtenu a partir de cultures liquides. L'activite theophylline demethylase a ete caracterisee a partir d'un extrait brut. La theophylline demethylase a ete purifiee jusqu'a homogeneite electrophoretique. C'est une proteine monomerique, de poids moleculaire de 40 a 43 kda, ayant un point isoelectrique compris entre 5,2 et 5,8. La sequence n-terminale et 5 sequences internes de la thd ont ete determinees. Ces dernieres presentent une homologie de sequence avec des proteines de la famille des nmt1.

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32

Tandt, Ludo Alfons Germaan Luc. "The evaluation of indomethacin and theophylline oral controlled/modified-release dosage forms in vitro-in vivo correlations." Thesis, Rhodes University, 1992. http://hdl.handle.net/10962/d1003272.

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Over the past few decades many researchers have investigated the utility of in vitro - in vivo correlations for the assessment of dosage forms. These investigations are, however, dependent on reproducible dissolution data and well conducted biostudies in order to establish meaningful and robust correlations. Despite the fact that the establishment of such correlations is perhaps idealistic, considerable interest has still been shown in this area of research. Various Controlled/Modified Release Dosage Forms (CMRD's) of theophylline, a weakly basic drug, and indomethacin, a weakly acidic drug, were assessed in order to establish in vitro - in vivo correlations. Dissolution rate studies were carried out using either the USP basket or paddle apparatus. The dissolution rate studies were conducted in a range of dissolution media of varying pH. Bioavailability studies were conducted on the dosage forms used by the Biopharmaceutics Research Institute at Rhodes University. The results of these biostudies were kindly made available for use in this research project. Type A correlations were established using a mathematical simulation process whereby expected in vivo responses are simulated and compared to actual profiles obtained for the dosage forms. In order to perform the simulations the dissolution rate profiles were stripped and using linear regression and the methods of residuals the dissolution rate order and the relevant dissolution rates were obtained. The results of the s imulations indicated that the in vivo serum concentration-time curves could be accurately predicted for the theophylline dosage forms but to a lesser extent, for the indomethacin formulations. The dissolution rate studies indicated that the paddle method is a suitable method for dissolution rate studies of theophylline CMRD's, although it appeared that the optimum pH of the dissolution medium was formulation dependent. Dissolution rate studies conducted on indomethacin formulations indicated that the USP specified basket method for extended-release indomethacin formulations was not able to distinguish between two formulations which exhibited different in vivo profiles. The conversion to the paddle method was, however, able to highlight the differences between these formulations. The use of three dimensional topographs to depict dissolution rate profiles was demonstrated for formulations of both theophylline and indomethacin. The topographs enabled the successful differentiation between bioinequivalent formulations. The dissolution rate profiles were also fitted to the Wei bull equation and the parameters obtained from this were compared to the Weibull parameters obtained from the in vivo absorption plots obtained using the Wagner-Nelson method. The results indicated that the Weibull function was suitable to describe both the in vivo and in vitro data. The following recommendations for the preformulation dissolution studies of weakly acidic and weakly basic drugs are proposed. The dissolution rate studies of weakly acid drugs, such as indomethacin, should be carried out over a range of pH utilising the paddle apparatus. Three dimensional topographs based on the dissolution data should be constructed and used as a comparative tool for different formulations. Based on these comparisons the appropriate formulation can then be selected for a pilot scale in vivo bioavailability study. The dissolution rate studies of weakly basic drugs, such as theophylline, should be carried out over a range of pH utilising the paddle apparatus. The dissolution data should then be used to simulate the expected in vivo profile and on this basis the appropriate formulation selected for a pilot scale bioavailability study. The above approach to the preformulation studies of new CMRO's would allow for the more careful selection of new dosage forms and could thus eliminate costly and unnecessary bioavailability studies performed on inferior formulations.

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33

Noël, Bernard. "Corrélation des taux salivaires et plasmatiques de théophylline chez l'enfant." Montpellier 1, 1991. http://www.theses.fr/1991MON11205.

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34

Yajid, Fatima. "Effets de l'hypodynamie et de la théophylline sur la respiration mitochondriale de muscles striés squelettiques de rats." Montpellier 1, 1999. http://www.theses.fr/1999MON1T022.

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35

Sullivan, Paul Joseph Gerard. "The effect of treatment with low dose theophylline on the inflammatory response to allergen in atopic asthma." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362934.

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36

Shearer, Luz-Elena Oropesa. "METHYLXANTHINE LEVELS IN BREAST MILK OF LACTATING WOMEN OF DIFFERENT SOCIOECONOMIC CLASSES (CAFFEINE, THEOBROMINE, PARAXANTHINE, THEOPHYLLINE, ETHNIC)." Thesis, The University of Arizona, 1985. http://hdl.handle.net/10150/275462.

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37

Douriez, Eric. "Mise en place d'une procédure d'établissement de la posologie et de surveillance des effets de différentes formes de théophylline dans trois services hospitaliers, de pédiatrie, de pneumologie et de réanimation néonatale." Paris 5, 1993. http://www.theses.fr/1993PA05P047.

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38

Pellerin, Frédéric. "Electrophysiologie cardiaque et ischémie provoquée dans le territoire de la coronaire droite : incidence de l'injection des phyllines." Montpellier 1, 1991. http://www.theses.fr/1991MON11183.

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39

Acheson, David William Kennedy. "The pharmacokinetics of theophylline and antipyrine and the pharmacogenetics of debrisoquine metabolism in patients with exocrine pancreatic disease." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/46925.

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40

Soderstrom, David. "Fuzzy logic modeling and intelligent sliding mode control techniques for the individualization of theophylline therapy to pediatric patients." Thesis, Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/19097.

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41

Barbosa, Eduardo José. "Avaliação da goma gelana como aglutinante em formulações de pellets contendo teofilina." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-28032017-163125/.

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O objetivo deste trabalho foi desenvolver formulações de pellets contendo teofilina, utilizando a goma gelana como aglutinante. Inicialmente, o uso desse polímero foi avaliado em comparação com o PVP. Por meio de delineamento experimental 32 foram analisadas as variáveis aglutinante e diluente. Os pellets obtidos apresentaram resultados satisfatórios na friabilidade e esfericidade. Verificou-se que o diluente exerceu influência significativa na granulometria, de modo que formulações com manitol apresentaram maior formação de pó após a produção. Com relação ao aglutinante sua maior influência foi na dissolução, pois formulações com gelana apresentaram eficiência de dissolução, em média, menor que as formulações com PVP. A seguir, foi avaliada a influência do polímero, sua quantidade, e seu modo de incorporação nas formulações. Para isso foi realizado um delineamento experimental 23, tendo a gelana, a quantidade, e a incorporação como variáveis. Verificou-se que a característica que sofreu maior influência das variáveis foi a granumoletria, pois as condições empregadas influenciaram significativamente o rendimento de pellets. Com relação à friabilidade, esfericidade e dissolução, não foram observadas diferenças significativas entre os resultados, ainda que algumas tendências puderam ser identificadas.
Aim of this work was to develop pellet formulations containing theophylline, using gellan gum as a binding agent. Inicially, application of the polymer was compared with PVP. By a 32 experimental design, variables binder and diluent were analyzed. Pellets presented satisfactory results in friability and sphericity. It was found that the diluent exerted significant influence on granulometry, so formulations with mannitol showed higher dust formation after production. Regarding binder variable, its higher influence was in the dissolution, since formulations with gellan presented smaller dissolution efficiency than formulations with PVP. Next, the influence of polymer, amount, and incorporation were evaluated. In this part, a 23 experimental design was carried out, with gellan, quantity, and incorporation as variables. It was found that granulometry was the most influenced by variables. So conditions employed influenced significantly the yield of pellets. Regarding friability, sphericity and dissolution, no significant differences were observed, although some trends could be identified.

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42

Parent, Xavier. "Determination de la concentration en forme libre de medicaments antiepileptiques et d'antiasthmatiques dans le serum et la salive." Strasbourg 1, 1992. http://www.theses.fr/1992STR15065.

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43

Van, Nieuwenhuyse Virginie. "Interaction pharmacocinétique entre le cisapride et la théophylline." Paris 5, 1994. http://www.theses.fr/1994PA05P248.

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44

Mauguen, Anne. "Innovations pharmacologiques et galéniques dans le traitement de la crise et de la maladie asthmatique." Paris 5, 1992. http://www.theses.fr/1992PA05P232.

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45

Rakotobe, Ratsimbazafy Voahirana. "Etude pharmacotechnique des gélucires : comportement rhéologie optimisation et mécanisme de libération de dérivés théophylliniques à partir de formes matricielles." Limoges, 1994. http://www.theses.fr/1994LIMO301A.

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46

Walker, Heather M. "A Preliminary Study of the Interaction of Acidic and Basic Drugs Using Ethyl Cellulose Microspheres." University of Toledo Health Science Campus / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=mco1352435064.

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47

SARANG, SANJAY S. "METHACRYLATE AND Ca-ALGINATE POLYMERS AS BARRIER COATINGS FOR PROTECTION AND CONTROLLED RELEASE OF VITAMIN C." University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1078246935.

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48

Wu, Hsiu-Jean. "The kinetics of solvent-mediated phase transformations." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/184981.

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The objectives of this work are to characterize and model the solvent-mediated phase transformation process of theophylline anhydrous crystals to the monohydrate crystals in an aqueous system. In order to model the transformation, the following processes are taken into account: (1) the dissolution kinetics of theophylline anhydrous crystals, (2) the kinetics of the formation of theophylline monohydrate nuclei, and (3) the growth kinetics of the monohydrate crystals. The driving forces for the above processes are determined from the concentration of theophylline in the solution and the solubilities of theophylline anhydrous and monohydrate. The solubilities of theophylline anhydrous and the monohydrate, and these three distinct processes along with the overall transformation phenomena were investigated in the present study. By using theophylline as a model compound we have gained some understanding of the kinetics of the solvent-mediated phase transformation between the metastable anhydrous form and the stable hydrated form of an organic compound and we were able to model the transformation process. By identifying the mechanisms for nucleation, growth of the hydrate form and the dissolution of the anhydrous form one can predict and control the transformation process. The growth kinetics of thymine monohydrate crystals at various temperatures are also investigated in the present study.

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49

Mohamed, Noha N. A. "Pharmaceutical analysis and in-vitro aerodynamic characterisation of inhaled theophylline formulations containing drug particles prepared by supercritical fluid processing. Chromatographic, spectroscopic, and thermal analysis of micron-sized theophylline particles prepared by supercritical fluid technology and in-vitro evaluation of their performance as inhaled dry powder formulations." Thesis, University of Bradford, 2009. http://hdl.handle.net/10454/4297.

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The aim of this work is to study the in-vitro aerodynamic performance of a new inhaled theophylline formulation prepared by supercritical fluids technique. For the analysis of the output from the in-vitro tests (and further in-vivo tests) a new, fast, sensitive high performance liquid chromatographic (HPLC) method was developed and validated for the determination of theophylline and other related derivatives in aqueous and urine samples using new packing materials (monolithic columns). These columns achieve efficient separation under lower backpressure and shorter time comparing to other traditionally or newly introduced C18 columns. Solution enhanced dispersion by supercritical fluid (SEDS) process has been applied for the production of anhydrous theophylline as pure crystals in the range 2-5 ¿m to be used as new inhaled dry powder formulation for asthma. Fifteen theophylline samples have been prepared under different experimental conditions. The drug produced by this method has been subject to a number of solid-phase analytical procedures designed to establish the crystal structure [X-ray powder diffraction (XRPD)], the structure and conformation [(FTIR), Fourier-transform Raman spectroscopy (FT-Raman)], and the morphology and particle size [scanning electron microscope (SEM)]. While, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) have been used to monitor any phase transition or polymorphic changes after processing. All these analytical techniques gave a satisfactory indication of the solid-state chemistry of the processed particles and assess the development of new inhalation product. The performance of inhaled SEDS theophylline with or without a carrier was evaluated using the developed HPLC method. Three samples having different particle sizes were selected out of the prepared powders by SEDS technique to be tested. The dose sampling unit and the Anderson Cascade Impactor were used to determine the in-vitro emitted dose and the deposition profiles of SEDS samples, respectively. The effect of different inhalation flows was studied using two different flows 28.3, and 60 L min-1 with 4 L inhalation volume. Different DPI devices were investigated in this study; Easyhaler® and Spinhaler®. The particle size has an important effect on the aerodynamic behaviour and deposition profile of inhaled drug, the smaller the particles the greater the total lung deposition. The presence of a carrier improves the respirable fraction for all the tested formulations.
Egyptian Ministry of Higher Education

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50

Mohamed, Noha Nahedj Atia. "Pharmaceutical analysis and in-vitro aerodynamic characterisation of inhaled theophylline formulations containing drug particles prepared by supercritical fluid processing : chromatographic, spectroscopic, and thermal analysis of micron-sized theophylline particles prepared by supercritical fluid technology and in-vitro evaluation of their performance as inhaled dry powder formulations." Thesis, University of Bradford, 2009. http://hdl.handle.net/10454/4297.

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The aim of this work is to study the in-vitro aerodynamic performance of a new inhaled theophylline formulation prepared by supercritical fluids technique. For the analysis of the output from the in-vitro tests (and further in-vivo tests) a new, fast, sensitive high performance liquid chromatographic (HPLC) method was developed and validated for the determination of theophylline and other related derivatives in aqueous and urine samples using new packing materials (monolithic columns). These columns achieve efficient separation under lower backpressure and shorter time comparing to other traditionally or newly introduced C18 columns. Solution enhanced dispersion by supercritical fluid (SEDS) process has been applied for the production of anhydrous theophylline as pure crystals in the range 2-5 μm to be used as new inhaled dry powder formulation for asthma. Fifteen theophylline samples have been prepared under different experimental conditions. The drug produced by this method has been subject to a number of solid-phase analytical procedures designed to establish the crystal structure [X-ray powder diffraction (XRPD)], the structure and conformation [(FTIR), Fourier-transform Raman spectroscopy (FT-Raman)], and the morphology and particle size [scanning electron microscope (SEM)]. While, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) have been used to monitor any phase transition or polymorphic changes after processing. All these analytical techniques gave a satisfactory indication of the solid-state chemistry of the processed particles and assess the development of new inhalation product. The performance of inhaled SEDS theophylline with or without a carrier was evaluated using the developed HPLC method. Three samples having different particle sizes were selected out of the prepared powders by SEDS technique to be tested. The dose sampling unit and the Anderson Cascade Impactor were used to determine the in-vitro emitted dose and the deposition profiles of SEDS samples, respectively. The effect of different inhalation flows was studied using two different flows 28.3, and 60 L min-1 with 4 L inhalation volume. Different DPI devices were investigated in this study; Easyhaler® and Spinhaler®. The particle size has an important effect on the aerodynamic behaviour and deposition profile of inhaled drug, the smaller the particles the greater the total lung deposition. The presence of a carrier improves the respirable fraction for all the tested formulations.

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