Effects of gastrointestinal transit on plasma concentrations of drugs from enteric-coated pellet formulations were demonstrated using pharmacokinetic models describing plasma concentrations of drugs from various enteric-coated pellet formulations. Gastric emptying time, lag time of emptying, and drug release rate from pellets in the small intestine, along with other pharmacokinetic parameters of drugs, were used to construct pharmacokinetic models. The models were then evaluated by comparing simulated plasma concentrations of model drugs from Monte Carlo simulations to observed plasma concentrations of these drugs from the literature. Results showed that the models described plasma concentrations of drugs from enteric-coated pellet formulations very well. Pharmacokinetic models describing plasma concentrations of drug from mixed immediate-release and enteric-coated pellet formulations were also used in simulations of bioequivalence studies. Results from the research are very useful in designing generic products of mixed pellet formulation and in refining or selecting the final product for actual bioequivalence study. Development of crushable enteric-coated formulations was presented. Nonpareil sugar pellets were spray-loaded with mixed amphetamine salts. Drug-loaded pellets were subsequently spray-coated with enteric polymer, hydrophilic gel-forming polymer, enteric polymer and/or mixture of insoluble polymer and hydrophilic polymer. The resulting pellets were then spray-coated with disintegrant and compressed to form crushable tablets. Dissolution testing of both non-compacted crushable enteric-coated tablets and crushed tablets showed that the intact crushable tablet formulations and the crushed tablet formulations were able to prevent the majority of the drug from being released in a simulated gastric dissolution medium within first 2 hours. Concept and formulations of "leaky" enteric-coated pellets were presented. "Leaky enteric-coated pellets" formulation is defined as enteric-coated pellets that allow some of the drug to be released from the formulation in acidic dissolution medium. Different approaches of making leaky enteric-coated pellets using spray-coating techniques were presented. Plasma concentrations of drug from leaky enteric-coated pellet formulations were simulated using computer simulations. The present research was based on the hypothesis that leaky enteric-coated pellets formulations were able to provide sustained-release effect on plasma concentration profiles of drugs that have the absorption window without jeopardizing their bioavailability or with improved bioavailability. / Graduation date: 2005

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Dry powder coating of pharmaceutical dosage forms has been investigated as an alternative method to commonly used liquid based coating techniques. Eudragit[trademark] L 100-55 and Eudragit[trademark] L 30 D-55 have been employed in enteric film coatings using aqueous dispersions, organic solutions and compression coating. However, the copolymer has not been investigated in dry powder coating applications. Initially, formulation factors and processing parameters were investigated for the dry powder coating of chlorpheniramine maleate tablets using Eudragit[trademark] L 100-55 as the delayed release polymer. Powder coating was studied as a method to prevent the migration of an ionizable, highly water soluble model drug into the polymeric film during the coating process. Eudragit[trademark] L 100-55 was pre-plasticized with triethyl citrate (TEC) using hot-melt extrusion and subsequently ground into a fine powder. Polyethylene glycol 3350 (PEG 3350) was used as a primer and low melting coating excipient to enhance coating powder adhesion and to improve film formation. The powder coating process was performed in a modified laboratory scale spheronizer. For the dry-powder coating of sodium valproate tablets different subcoating materials were investigated to improve powder adhesion to the substrate and to reduce the level of Eudragit[trademark] L 100-55 required for gastric resistance. PEG 3350 and Methocel[trademark] K4M were incorporated in the Eudragit[trademark] E PO and Eudragit[trademark] RL PO subcoating formulations as pore forming materials. The miscibility of the PEG 3350 and Methocel[trademark] K4M in the film coating was correlated with their ability to function as pore forming agent. The film formation process of thermally cured Eudragit[trademark] L 100-55 dry-powder coatings was characterized. The influence of film additives on relative melt viscosity, surface free energy of the polymer and the mechanical properties of powder-cast films was studied. The influence of Eudragit[trademark] E PO in Eudragit[trademark] L 100-55 film coatings applied by a dry powder coating technique on the drug release mechanism was investigated. Calculation of the Flory-Huggins interaction parameter based on solubility parameters and different analytical techniques demonstrated immiscibility of the copolymers at processing conditions. A broad range of pH dependent theophylline release profiles were obtained as a function of the polymer blend ratio. / text

Thesis (Ph. D.)--University of Rhode Island, 2006. / Typescript. Includes bibliographical references (leaves 210-235).

Thesis (M.S.)--Rutgers University, 2006. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 89-93).

This dissertation describes two different projects. The first is the development of an oral DNA vaccine delivery system for fish. A novel oral DNA vaccine delivery system was developed for Rainbow Trout by combining non-viral vectors (polycationic liposomes or polycationic polymer) to facilitate the DNA vaccine's uptake by cell membranes along with enteric-coated protection of the DNA embedded in microparticles to prevent DNA degradation in the gastrointestinal tract. Spray drying and spray coating bead techniques were employed in the preparation of the DNA vaccine microparticles. The spray drying technique allowed production of spherical shape enteric-coated microparticles with a particle size range of 0.18 to 20 ��m. Larger particle sizes of 40-50 mesh were obtained from the spray-coated bead technique. The resultant DNA vaccine microparticles were granulated with regular fish feed and given to fish to investigate the efficacy of the delivery system in providing protection against IHNV, and to demonstrate the ease of administration in fish. An in vivo fish trial experiment showed improvement in fish survival rate when fish were immunized with larger particle size DNA vaccine microparticles. Further research to find effective vector carriers for the DNA vaccine delivery system and to seek modifications of the delivery system that will still prevent the denaturation of plasmid DNA that will also facilitate membrane uptake of the DNA vaccine is needed in order to develop a safe, effective, and commercially viable vaccine to control the outbreak of IHNV. The second project of the dissertation is prediction of in vitro drug release profiles from a novel matrix tablet spray-coated with a barrier membrane using mathematical and statistical models. Tablets were prepared by direct compression followed by spray coating. The relationship of the amount of hydrophilic materials in the core tablets and barrier thickness on drug release mechanism was investigated using factorial design and regression analysis. Drug release characteristics were influenced and can be controlled by modifying the amount of hydrophilic materials in the core tablet and the barrier thickness. Mathematical equation generated from regression analysis of n-value, lag time, and percent drug release as a function of the amount of hydrophilic material and the amount of coating material applied can now be used as a tool for predicting and optimizing in vitro drug release from matrix tablets spray-coated with a barrier membrane. / Graduation date: 2003