Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographies: leaves 56, 78.

Controlled and sustained release dosage forms are the focus of worldwide research. These dosage forms facilitate patient compliance by simplifying the dosage regimen, and decrease the risk of adverse effects by reducing large fluctuations in the plasma concentration of the drug. The objective of this study was to formulate a repeat-action tablet to provide a sustained release dose of pseudoephedrine sulfate (PSS), and an immediate release dose of both PSS and loratadine. The release profile was compared to that of a commercially available preparation, Clarityne-D®. This formulation developed presents a novel mechanism of sustaining the release of PSS. The prototype tablet consisted of a sustained release core coated with an ethylcellulose dispersion to introduce a lag phase into the release profile and a second outer film coat incorporating PSS and loratadine. The core comprised an ethylcellulose granulation of PSS compressed into a hydroxypropyl methylcellulose matrix. The release of PSS from prototypes was assessed using USP Apparatus 3, as this apparatus was more representative of in vivo conditions and discriminated more effectively between the different tablet compositions produced during development. All dissolution samples were analysed for PSS and loratadine using validated highperformance liquid chromatographic methods. The prototype sustained release cores were found to be more resistant than the reference product to elevated temperature and humidity (40°C/87% RH) with fewer observed changes to the release profiles following storage for up to six months. This study was a feasibility study to obtain proof of concept. The release profile obtained from the prototype tablets was similar (f₂ = 50.0) to that of the reference product. Further development and optimisation of this dosage form is necessary, including evaluation of the choice of hydrophobic polymer, the effect of compression force and tablet geometry and characterisation of the release mechanism from the coated matrix. Assessment of these factors is necessary in order to optimise the formulation with respect to the desired therapeutic objectives.

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Chemical and Biochemical Engineering." Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin. / Includes indexes. Bibliography: p. 67-144.

Thesis (Ph.D. (Pharmacy)) - Rhodes University, 2006.

Aspen Pharmacare, one of the leading pharmaceutical manufacturers in South Africa has embarked on a programme of improving the production processes currently employed at their Port Elizabeth site. With the introduction of new technology at the site and the move towards globalization, it became imperative that Aspen remain competitive in the market. The product of interest in this research, Degoran Plus tablets, is one of the company’s leading brand sellers. Upon investigation, it became apparent that this product created opportunity for process improvement using the new technology. The manufacture of Degoran Plus entails granulation, compression and coating of the product. Most opportunity for improvement was possible in the granulation stage because of the laborious nature of the present process. Degoran Plus tablets had a history of analytical failures, especially with regard to the dissolution rate of the final product, as well as other quality related issues. The product was not considered to be a “through-runner”, which resulted in bad production output, due to continual repeats of not only analysis but also reworks in production. A strategic decision was taken to manufacture Degoran Plus using the Collette Gral granulator as the equipment offered superior mixing capability when compared to the Bear planetary granulator. It was assumed that the granulation process would result in more uniform distribution of the actives. Upon producing a better granule, a final product of superior quality would be attained. The validation protocol stipulates that three samples be taken and tested from the powder mix. Nine samples taken from granulated bulk are treated in the same manner. The validation protocol further stipulates that the first three batches manufactured utilise the new process, and tested according to the protocol. The results obtained from the analysis are evaluated statistically and a conclusion and recommendation were derived based on the evaluation.

The dissolution profile of orally delivered drugs can be controlled through the use of osmotically controlled drug delivery devices. The most commonly used device is the osmotic tablet, which is essentially a tablet core that is coated with a rate-limiting semipermeable membrane. The feasibility of applying a coating onto a tablet using dense gas techniques was studied. Two different coating materials, polymethymethacrylate (PMMA, Mw = 120,000 g/mol) and cellulose acetate (CA, 39.8 wt% acetyl content) were applied onto an 8 mm osmotic tablet core using the Gas Anti-solvent (GAS) process. For PMMA, the pressurisation rate, coating temperature and volumetric expansion of up to 250% had minimal effect on the coating quality. The concentration, solvent type and the use of polyethylene glycol (Mw = 200 g/mol) had a more pronounced effect on the coating. The coating process was optimised to apply a smooth and uniform coating with a 50 ??m thickness. For CA, the pressurisation rate and the coating temperature had little effect on the coating that was applied. The process was more sensitive to a change in the concentration of the solution and the volumetric expansion that was used. It was found that the concentration could not be increased too much without affecting the coating quality. A CA coating was applied onto a PMMA-coated tablet using the optimised conditions. The thickness in the tablet coating increased by 10 ??m. Dissolution tests of the uncoated and coated tablets were carried out. The CA coatings were found to be insufficient in limiting the rate of water entering the tablet and performed similarly to an uncoated tablet core. The PMMA coatings were found to limit the rate of delivery of the model drug. However, variations in the PMMA coatings resulted in an inconsistent delivery profile across batches. The tablets coated with both PMMA and CA had a delivery rate in between that of uncoated and PMMA-coated tablets, indicating that the application of the second coating had compromised the initial PMMA coating.

This dissertation is comprised of four distinct formulation sections, which are described below: A novel solid dosage formulation was investigated for achieving zero-order drug release profile by combining tablet shape design and tablet membrane film coating. Verapmail (model drug) was compressed into hydrophilic matrix tablet cores of flat-faced and bi-convex shape, which were encapsulated with membrane controlling film. The hydrophilic tablet core contained hydroxypropyl methylcellulose (HPMC) 15 LV, pectin, and Avecil��. The membrane film coating solution was comprised of deionized water, Opadry��, Surelease�� and talc. The combination of membrane film coating and tablet shape design was found to influence in vitro verapamil release profile towards the zero-order release demonstrated by the commercial Covera HS�� (Pharmacia). An alternative formulation for the commercial Bactroban�� (Smithkline Beacham) ointment 2% was developed. Both the texture and consistency of the new ointment were comparable to the Bactroban�� ointment. The new and the commercial formulations were found to be equivalent in drug release by the Bauer-Kirby test. Mupirocin remained unstable in the new formulation. Mg����� was added to help stabilize mupirocin and was shown to complex with mupirocin by nuclear magnetic resonance (NMR). The modified formulation including Mg����� however failed to stabilize mupirocin. The stability assay results showed an average of 67.2% mupirocin recovery along with 25.2% degradation products. A generic omeprazole formulation was developed, which was comprised of nonpareil core, omeprazole matrix layer, and an enteric locating layer of ammoniated hydroxypropyl methylcellulose phthalate (HPMCP) 55S. The new formulation was gastro-resistant in protecting against omeprazole degradation for up to 2 h, but failed to dissolve as rapidly as the commercial Prilosec�� (Astra Merk) in simulated intestinal fluid. The addition of expotab�� to the enteric coating layer failed to improve omeprazole dissolution rate. A novel hot-melt coating methodology utilizing direct blending technique has been developed. The processing steps for the direct blending hot-melt coating are: (a) Hot-melt system preparation; (b) Dispersion/dissolution of the active ingredient(s) in the hot-melt system; (c) Pre-heating of the coating substrate; and (d) Cooling and congealing of the hot-melt on substrate surface. Immunogenic effect was observed in mice administered with enteric-coated ragweed pollen extract (RPE) alpha fraction by the hot-melt coating encapsulation with direct blending method. The effect was not shown to be statistically significant. / Graduation date: 2003

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

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