Date of Award
Master of Science in Pharmaceutics
Christopher T. Rhodes
The interaction between drugs and excipients or between drugs and other drugs in the same dosage form have potential to modify safety and efficacy. In some cases the interaction can be of such a degree as to preclude the use of some excipients or to dramatically reduce the shelf life of the products. Thus there is clearly a need for techniques which can reduce or eliminate such interactions.
Sometimes the irrational combination of two drugs or drug and excipient cause a decrease in the stability, bioavailability and efficacy of the dosage form1. Microencapsulation can be considered as a tool to enhance the drug stability2. It has generally been observed that microencapsulated products show a substantial reduction or elimination of the adverse effects of incompatibilities, although quantitative data on the extent of stabilization is not readily available in the published literarture.
The primary objective of this study was to determine the drug interactions and incompatibilities between drugs and excipients which are widely used in pharmaceutical manufacturing and have some characteristic compatibility problems. I did these studies on powder mixes and compressed tablets owing to the fact that majority of the dosage forms are formulated in the solid state3. The study included three drugs namely aspirin, acetaminophen and pseudoephedrine (hydrochloride salt).
The interaction between aspirin and dibasic calcium phosphate (Emcompress) was studied in detail. Non-microencapsulated aspirin showed significant degradation by hydrolysis in presence of Emcompress at room temperature as well as elevated temperature. Microencapsulated aspirin showed a marked decrease in the degradation under same conditions. The stabilizing effect of the microencapsulation was both statistically significant and substantial.
The interaction between acetaminophen (APAP) and diphenhydramine hydrochloride and phenylephrine hydrochloride was monitored for the presence of degradation products. These agents showed incompatibility with acetaminophen when used in the proportion which was the same as that of an over the counter product. The manifestation of incompatibility was melting point depression by eutectic formation. The eutectic formation was prevented when microencapsulated acetaminophen was used.
Non-microencapsulated acetaminophen showed significant adsorption over antacids like aluminum hydroxide, magnesium trisilicate and calcium carbonate. Microencapsulated acetaminophen demonstrated appreciable decrease in the rate and extent of adsorption under similar conditions.
I had planned the compatibility studies of pseudoephedrine HCI with hydrous lactose and with sodium metabisulphite. The literature showed evidence of some degradation products. However initial tests showed no significant compatibility problems and hence no further experimentation was performed on these substances. However the interaction of pseudoephedrine and acetaminophen and pseudoephedrine and aspirin was monitored for the degradation products.
A battery of in process quality control tests such as appearance, weight variation, content uniformity, surface characters, flowability, friability, and moisture content were performed on all three formulations. All results were evaluated using conventional statistical techniques using factorial design and the differences between microencapsulated and non microencapsulated products were determined at 95% confidence intervals. Both the groups were compared using tests such as ANOVA (Analysis of Variance), Student's t test (two tailed), and simple regraession analysis with the help of a software on a microcomputer.
Pimplaskar, Harish K., "STUDY OF MICROENCAPSULATED PRODUCTS WITH RESPECT TO THEIR ABILITY TO PREVENT INCOMPATIBILITIES" (1994). Open Access Master's Theses. Paper 277.