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Polymer gels as pharmaceutical dosage forms : rheological performance and physicochemical interactions at the gel-mucus interface for formulations intended for mucosal drug delivery /Hägerström, Helene, January 2003 (has links)
Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 7 uppsatser.
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TabletsFoote, Perry Albert. January 1928 (has links)
Thesis (M.S.)--University of Wisconsin. / Includes indexes. Bibliography: p. 67-144.
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Factors influencing the biodistribution of liposomal systemsSommerman, Eric Frank January 1986 (has links)
Liposomes have important potential as drug delivery vehicles. However, in order to realize this potential, much basic research is required to elucidate the interactions experienced by liposomes in vivo. In this thesis two aspects of these interactions are investigated: the influence of vesicle size and lipid composition on the biodistribution observed in vivo; and the interaction of liposomes with plasma proteins.
In order to determine the in vivo behavior of liposomal systems, a new vesicle marker is synthesized (¹²⁵I-tyraminyl-inulin, ¹²⁵ITI) and tested in vivo. It is shown that this probe satisfies the necessary criteria for an accurate marker of liposome behavior, and is superior to probes used by other workers in terms of accuracy, convenience, high specific activity, low tissue quenching and cost. The use of ¹²⁵ITI as a vesicle marker allows accurate measurements to be made with lower doses of liposomes than previously employed. The influence of vesicle size, composition, and dose on the blood residency times, leakage and tissue distributions of vesicles was therefore investigated at these lower doses, employing a cannulation procedure to monitor vesicles. It is demonstrated that the clearance of vesicles from the circulation exhibits biphasic kinetics. The relative number of vesicles cleared during the early phase (halflife <20 min) is decreased by increasing the vesicle dose or decreasing the size. The behavior of small vesicles produced by extrusion is also investigated, and the in vivo behavior of these systems is shown to be equivalent to conventional sonicated systems.
The second part of this thesis investigates the binding of plasma proteins to vesicles in vitro. It is shown that vesicles bind a large number of plasma components and that the binding is strongly dependent on the surface charge of the vesicle. Some of the proteins have been tentatively identified with 2-D electrophoresis and several were positively identified via immuno- autoradiography. A hypothesis is advanced regarding the role of plasma proteins in the fate of liposomes in vivo. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate
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Dosage forms in therapy of posterior segments of the eyePospěchová, Lucie January 2016 (has links)
1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Lucie Pospěchová Title of Thesis: Dosage forms in therapy of posterior segments of the eye. Therapy of the posterior eye segments is very difficult. Because most of diseases of the posterior eye segments could lead to complete blindness, the research of dosage forms for the drug delivery into this eye part is intensively developing at this moment. The aim of this thesis is to provide a review of anatomical and physiological specifics of both- anterior and posterior segments of the eye. The most common diseases of the posterior eye are referred to, for example the age related macular degeneration and/or the cytomegalovirus retinitis. There are various routes of application and drug dosage forms that are used for the therapy and which are mentioned in this work, including the drug delivery and targeting systems.
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Farmacomagnetografia colônia : estudo in vitro da desintegração de comprimidos magnéticos revestidos /Andreis, Uilian de. January 2010 (has links)
Orientador: José Ricardo de Arruda Miranda / Banca: Luciana Aparecida Corá / Banca: Ricardo Brandit de Oliveira / Banca: Cristina Helena dos Reis Serra / Banca: José Ricardo Corrêa Saglietti / Resumo: A avaliação dos parâmetros motores do trato gastrintestinal é condição necessária para caracterizar o comportamento de formas farmacêuticas sólidas administradas pela via oral. A função motora gastrintestinal pode ser alterada em detrimento de doenças, interações com medicamentos ou intervenções cirúrgicas. Essas alterações, por sua vez, podem influenciar diversos processos farmacêuticos e, consequentemente, a biodisponibilidade dos fármacos. Comprimidos são as formas farmacêuticas mais utilizadas na terapia. Para garantir a eficácia e segurança dessas preparações, são necessários testes in vitro que simulam o trato gastrintestinal. Entretanto, não é possível estimar com precisão a influencia dos parâmetros gastrintestinais na liberação do fármaco. Por essa razão, os ensaios in vivo realizados por técnicas não invasivas e inócuas ao indivíduo são necessários, pois permitem monitorar simultaneamente os parâmetros motores e suas interrelações com os processos de liberação e biodisponibilidade dos fármacos. O objetivo desse trabalho foi empregar a técnica de Biosusceptometria AC associada à farmacocinética para avaliar a influência da motilidade gastrintestinal, bem como das alterações induzidas nessa função pela administração prévia de um procinético (Domperidona) e um antimuscarínico (Butilbrometo de Escopolamina). Além disso, foram avaliadas as influências desses parâmetros no processo de liberação e biodisponibilidade de um fármaco modelo (Diclofenaco Sódico) adicionado a comprimidos revestidos / Abstract: The evaluation of gastrointestinal motor parameters is necessary towards characterize the behavior of solid dosage forms orally administered. The gastrointestinal motor function may be altered by diseases, drugs or surgery. These alterations may influence a number of pharmaceutical processes and consequently the bioavailability of drugs. Tablets are the dosage forms most commonly used in therapy. To ensure the efficacy and safety of these formulations, in vitro tests in simulated gastrointestinal conditions are needed. However, such conditions as well as the influence of gastrointestinal parameters on drug release cannot be fully predicted. For these reasons, in vivo studies are realized by noninvasive and harmless techniques, since they allows monitoring gastrointestinal motor parameters and the relationships with drug delivery and bioavailability. The aim of this work was to employ the AC Biosusceptometry to evaluate the influence of gastrointestinal motility as well as the induced changes on this function by previous administration of a prokinetic drug (domperidone) and an antimuscarinic agent (scopolamine butilbromide). In addition, it have been evaluated how these alterations influenced the drug release and bioavailability of a model drug (sodium diclofenac) added to coated tablets / Doutor
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Product formulations and in vitro-in vivo evaluation of a novel "Tablet-in-a-Bottle" suspension formulation of amoxicillin and clavulanic acidYang, Ning-Ning 11 June 1997 (has links)
This thesis describes a novel "Tablet-in-a-Bottle" oral suspension formulation.
Ingredients with unstable physical or chemical characteristics can be placed in a core tablet, and then dry compression coated with an outer layer which provides separation from other components. The new suspension formulation comprises fast disintegrating clavulanic acid (KCA) tablets with a powder mixture containing amoxicillin. Hardness, friability, flow properties and weight uniformity of tablets for three different formulations were investigated and were all improved in a third formulation. Stability tests under different humidities were conducted. Amoxicillin and clavulanic acid in the new formulations showed the same stabilities when compared with the marketed product Augmentin��. Preliminary pharmacokinetics and bioavailability of one new formulation were evaluated by comparing in vitro release rates and in vivo urinary excretion rates. In vitro dissolution studies were carried out according to the USP XXIII paddle method. The new formulation showed faster release rates during the first hour when stirring speed was 25 rpm. However, when 75 rpm stirring speed was applied, the dissolution
profiles for the new formulation and the reference marketed product were identical. A randomized two-way crossover bioequivalence study was designed to evaluate the bioavailabilities. Cmax, Tmax and AUC[subscript o--->t] of amoxicillin were within ��20% of the reference pharmacokinetic values. However, Cmax and Tmax of clavulanate were not within ��20%. Bioeqivalence between this new suspension formulation and the marketed product (Augmentin��) were evaluated using a two one-sided t-test. There is not sufficient statistical support with this test to conclude that the two products are bioequivalent. However, this is most likely due to small sample size and high intersubject variation and statistical support for bioequivalence is expected in a larger study group. / Graduation date: 1998
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Oral delivery of protein-transporter bioconjugates using intelligent complexation hydrogelsShofner, Justin Patrick, 1983- 02 October 2012 (has links)
Several polymer systems including P(MAA-g-EG) and P(MAA-co-NVP) with crosslinking agents TEGDMA and PEGDMA1000, monomer-to-solvent ratios of 67:33, 60:40, and 50:50, and particle sizes of <75 microns, 90-150 microns, and 150-212 microns were synthesized for use with protein-transporter conjugates. All synthesized systems were characterized by SEM which demonstrated the visual size, surface features, and surface textures of the polymer microparticles. Insulin-transferrin and calcitonin-transferrin conjugates were successfully synthesized using the protein crosslinker SPDP, binding the two proteins with a disulfide bond. The multi-step conjugation reactions used to create the conjugates were analyzed by the use of UV spectroscopy and HPLC to ensure the quality of the final products. In both conjugation reactions, the final product yield was found to be over 70%. The in vitro loading and release characteristics for insulin-transferrin and calcitonin-transferrin were separately investigated. By testing loading and release using a number of different polymer systems with different synthesis parameters, it was possible to optimize the hydrogel carriers for use with each of the conjugates independently. Upon optimization, the ideal system for use with insulin-transferrin and calcitonin-transferrin was found to be P(MAA-g-EG) microparticles of <75 microns formed using a PEGDMA1000 crosslinker and a 50:50 monomer-to-solvent ratio for both conjugates through separate optimization processes. This optimized polymer carrier was found to release upwards of 50% of loaded insulin-transferrin conjugate and near 90% of loaded calcitonin-transferrin conjugate. The insulin-transferrin conjugate was further evaluated through the use of cellular and animal models. Using cellular models, the insulin-transferrin conjugate was shown to increase transport relative to insulin by a factor of 7, achieving an apparent permeability of 37 x 10⁹ cm/s. Also, in the presence of polymer microparticles, the insulin-transferrin conjugate increased transport by a factor of 14 times relative to insulin, achieve an apparent permeability of 72.8 x 10⁹ cm/s. The presence of the microparticles near the cells was found to improve conjugate transport by nearly 100%. The preliminary animal studies verified the successful synthesis of the insulin-transferrin conjugate as well as demonstrated the bioactivity of the insulin portion of the molecule by achieving a drop in blood glucose level upon subcutaneous injection. / text
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Methylcellulose as a troche baseTrotter, Gerard Francis, 1922- January 1955 (has links)
No description available.
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Development of a high pressure liquid chromatographic method for the simultaneous analysis of sulphamethoxazole and trimethoprim and its application to biological fluids and dissolution rate studies on solid oral dosage formsGochin, Rosa January 1980 (has links)
Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
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Development and assessment of azithromycin paediatric suppository formulationsMollel, Happiness January 2006 (has links)
The use of the oral route of administration for the treatment of young children with antibiotics can at times be problematic since, factors such as nausea, vomiting, taste and/or smell, in addition to the challenges associated with the administration of suspensions, may contribute to poor patient compliance. In such cases, the use of the rectal route of administration may be appropriate. Therefore, suppositories containing 250 mg azithromycin (AZI) were manufactured and assessed for potential as an antibiotic suppository dosage form. Suppositories, containing AZI dihydrate were manufactured by the fusion method, using different grades of PEG, Witepsol® and Suppocire® bases. The rate and extent of AZI release was evaluated using USP apparatus I, and samples were analyzed using a validated HPLC method. Differences in the rate and extent of AZI release were observed with the greatest amount of AZI being released from PEG formulations. The rate and extent of AZI release from formulations manufactured using fatty bases were influenced by physicochemical properties, such as melting rate and hydroxyl value, of the bases. In addition drug partitioning appeared to favor the lipid phase and had a negative impact on AZI release characteristics. Two different formulation approaches were used in an attempt to increase the rate and extent of AZI release from fatty base formulations. The use of surfactants significantly increased AZI release from formulations manufactured with fatty bases with high hydroxyl values. The use of urea or Povidone K25 in combination with AZI as a physical mixture or solid dispersion did not increase the rate and extent of AZI release from the fatty suppositories, to any significant extent. The mechanism of drug release was evaluated using several mathematical models, including the Higuchi, Korsmeyer- eppas, Zero and, First order models. In addition, in vitro dissolution profiles were characterized by the difference and similarity factors, f1 and f2 and by use of the Gohel similarity factor, Sd. AZI release kinetics were best described by the Higuchi and Korsmeyer-Peppas models and the values of the release exponent, n, revealed that drug release was a consequence of the combined effects of AZI diffusion, rate of melting of the base and partitioning of the drug which can be considered to be anomalous release.
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