Electronic Theses and Dissertations

Date of Award

2019

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Pharmaceutics and Drug Delivery

First Advisor

Michael A. Repka

Second Advisor

Walter Chambliss

Third Advisor

Soumyajit Majumdar

Relational Format

dissertation/thesis

Abstract

As the buccal route of administration can avoid the first pass effect, the bioavailability of drugs that are metabolized in the liver can be increased through this route. Few studies have been conducted using oleic acid as a permeation enhancer in any trans-buccal dosage form. The objective of this study was to develop a buccal tablet using two concentrations of oleic acid for a model drug (Ondansetron) via melt extrusion technology and investigate the effects of oleic acid on the physicochemical properties of the tablet. Formulations consisting of the active drug (ondansetron hydrochloride), polymers and oleic acid were prepared by extrusion. Bioadhesion studies were conducted and results obtained were satisfactory. Permeation studies demonstrated a greater drug permeation in the formulation containing a lower concentration of oleic acid. In conclusion, permeation studies exhibited the potential of oleic acid as a buccal permeation enhancer and the melt-extrusion technology was successfully employed to formulate buccal tablets. Conventional techniques of poloxamer gel preparation have disadvantages such as costly equipment and scale-up issues. Therefore, the objective of this work was to develop poloxamer gels by extrusion technology. Formulations consisted of poloxamer with ketoprofen (active drug). On increasing the poloxamer concentration, a decrease in the drug permeation was obtained. Other studies conducted were in-vitro release studies, texture analysis, and rheological studies. In conclusion, this technology could be successfully employed to develop poloxamer gels by overcoming the drawbacks associated with conventional techniques. However, it is not yet widely used for semisolid production. Therefore, the aim of the next project was to combine quality by design principles with extrusion to study the effect of the process parameters on cream characteristics. Eight formulations were obtained using a 23-factorial design. Only the temperature of zone 2 demonstrated a significant impact on the work of adhesion of the creams. A similar permeation profile was obtained with the formulations. Stable cream formulations were also obtained as demonstrated by the size distribution graphs. In conclusion, this technology coupled with a design of experiments approach can be utilized to investigate how extrusion parameters could be modified to develop consistent creams with ideal product characteristics.

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