No description available.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xix, 331 p.; also includes graphics (some col.). Includes abstract and vita. Advisor: Thomas McCain, Communication Graduate Program. Includes bibliographical references (p. 295-331).

Thesis--Nancy, 1937. / At head of title: Année 1936-1937, 3e série, no 1. Thèse ... par Mme Pinsolle, Solange ... "Index bibliographique": p. [13]-14. "Index bibliographique des ouvrages consultés pour le dépouillement de l'inventaire de Sebastien Sorel": p. [85]-94.

Thesis (Ph.D.)--University of Wisconsin--Madison, 1978. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 273-284).

Thesis (M.S.)--University of Wisconsin--Madison, 1965. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 277-282).

Issued also as thesis under title: Contribution à l'étude de l'évolution historique des techniques d'organisation sociale appliquées à la pharmacie. / "Bibliographie": p. [821]-850.

<p>The purpose of this thesis was to develop methods suitable for the incorporation of drug substancessuch as proteins into microparticles intended for controlled release. In particular a novel techniquefor the preparation of microparticles using supercritical fluids was investigated.</p><p>Supercritical fluids offer a considerable promise as extraction media for the formation ofmicroparticles of drugs and pharmaceutical excipients. There are two main reasons for using this technique. Firstly, the selective solvating power of supercritical fluids makes it possible to separatea particular component from a multi-component mixture. Secondly, the favourable mass transfer properties and high solubility of solvent in supercritical fluid make the formation of the microparticles rapid and efficient. </p><p>The Solution Enhanced Dispersion by Supercritical fluids process (SEDS) was used for the production of microparticles from several different biodegradable polymers. Briefly, particles were formed by the extraction of solvent from a solution which was sprayed into a supercritical fluid. </p><p>The use of a combination of supercritical N₂ and CO₂ in the SEDS process, improved the dispersion of polymer solutions, as compared with CO₂ alone. This resulted in reduction of the particle size of discrete microparticles produced from amorphous biodegradable polymers. Proteins (lysozyme and urease) were successfully incorporated into the poly(d,l-lactide-co-glycolide): copolymer composition 50:50 (DL-PLG) microparticles. The particles showed high entrapment efficiencies and the incorporated proteins retained a high degree of biological activity. Compared with conventional technologies for the preparation of such drug delivery systems, e.g. solvent-evaporation emulsion techniques, this new technique is environmentally superior, and suitable for up-scaling. Moreover the higher degree of control as indicated by the high reproducibility, makes validation of the process feasible. In conclusion, the SEDS process is an attractive way of incorporating proteins and peptides into biodegradable microparticles for controlled release.</p>

<p>In this thesis local anaesthetic formulations based on PEO-PPO-PEO block copolymers (PEO and PPO being poly(ethylene oxide) and poly(propylene oxide), respectively) or nonionic cellulose ethers undergoing temperature- or dilution-induced thickening were investigated. The aim of the work was to develop formulations which can be easily administered to the periodontal pocket, stay at the application site, give a fast onset of anaesthesia and have a duration sufficient to perform periodontal scaling procedures. </p><p>Emulsions, (mixed) micellar solutions and microemulsions fulfilling the requirements stated above were achieved by combining the active ingredients lidocaine and prilocaine with the nonionic block copolymers Lutrol^® F127 and Lutrol^® F68. The critical micellisation and gelation temperatures of the systems were found to be interconnected and influenced by the total polymer concentration and the polymer mixture composition, as well as the presence of cosolutes and pH. </p><p>A low-viscous isotropic phase that turns into a high-viscous hexagonal phase as the water content increases was found by combining Lutrol^® F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM. The system has a slower release rate compared to the microemulsion formulation which might make it suitable for indications where a longer duration is needed. </p><p>Finally, a temperature-induced gelling system was achieved by adding lidocaine and prilocaine to mixtures of ethyl(hydroxyethyl)cellulose (EHEC) and sodium dodecyl sulfate (SDS), hexadecyltrimethylammonium bromide (CTAB) or myristoylcholine bromide systems at, or just below, the surfactant concentration found to give a maximum viscosity increase at room temperature. In particular, the myristoylcholine bromide system may be interesting considering its antibacterial properties and biodegradability.</p>

<p>Less than 2% of the lead compounds generated by the pharmaceutical industry enter the exploratory drug-development phase, from which point they stand only a 10% chance of becoming a commercial medicine. A large proportion of the compounds fail due to poor biopharmaceutical properties, such as permeability and solubility. The main theme of this thesis is, therefore, the development of better experimental and computational methods for modelling and predicting the biopharmaceutical properties of drug candidates. Immobilised liposome chromatography (ILC) was used for studying drug-membrane interactions and for the prediction of passive drug transport. For the drugs studied in this thesis, ILC and octanol/water partitioning showed a similar performance with regard to the prediction of passive drug transport.</p><p>The theoretical work was directed at the modelling and prediction of drag transport processes using calculated molecular properties and PLS analysis. In the initial studies, the molecular properties were calculated with an advanced computational tool (MolSurf) that takes the three-dimensional structural information and electronic properties of the compound into consideration. Statistical models well suited to the prediction of drug transport processes such as Caco-2 cell permeability, intestinal absorption and CNS penetration were derived.</p><p>This approach was also successfully applied to the modelling of the interaction of drugs with P-glycoprotein. Subsequently, rapidly calculated descriptors based on two-dimensional structural information and PLS analysis were also found to give good predictive models of drug transport properties. The preferred use of the latter models is for screening compound collections and virtual libraries. It can be concluded that calculated molecular properties in conjunction with PLS analysis are well suited to the modelling and prediction of drug transport processes and to identifying compounds with potential biopharmaceutical problems at an early stage of the drug-development process.</p>

<p>Lead compounds generated in high-throughput drug discovery programs often have unfavorable biopharmaceutical properties, resulting in a low success rate for such drug candidates in clinical development. Efficient and reliable methods that predict biopharmaceutical properties, such as intestinal permeability and solubility are therefore required in order to reduce the attrition rate during development of these compounds.</p><p>One aim of this thesis was to identify molecular properties that are important for intestinal drug permeability using a wide range of drugs and model compounds. A second aim was to develop computational models for predicting intestinal drug permeability based on these properties.</p><p>The calculated molecular descriptors ranged from the simple counting of atoms and fragments to more complex descriptors derived from molecular mechanics and quantum mechanics calculations. Particular attention was given to descriptors associated with molecular surface areas. Descriptors calculated by the various methods were used to establish structure-permeability relationships for conventional drugs, peptide derivatives and large, lipophilic compounds generated by high-throughput pharmacological screening. Caco-2 cell monolayer permeabilities were determined for a structurally diverse set of compounds and were used to predict human intestinal membrane permeability and to develop computational models.</p><p>From these investigations, several new models for the computational prediction of intestinal membrane permeability were developed. Models were developed that are suitable for the prediction of membrane permeability to specific types of drugs, as well as models that are more generally applicable. One of these general models is based on partitioned total molecular surface areas, and this model can be used to predict intestinal membrane permeability to structurally diverse compounds. It was also demonstrated how these models can be applied in a manner that increases both the accuracy of the prediction and the throughput. In addition, a simplified protocol based on Caco-2 cells for the experimental prediction of intestinal permeability was developed. These improvements can be used to construct highly effective experimental and computational filters for use in drug discovery and development.</p>