Document Type

Thesis

Date of Award

Fall 12-31-2017

Degree Name

Master of Science in Pharmaceutical Engineering - (M.S.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Piero M. Armenante

Second Advisor

Boris Khusid

Third Advisor

S. Basuray

Abstract

Dissolution testing is a critical component of quality control procedures in the pharmaceutical industry in order to ensure that the final solid dosage forms have consistent dissolution properties. Dissolution tests are also routinely conducted to evaluate the in-vitro performance of solid dosage forms during pharmaceutical development, to aid in the behavior of formulations, and to optimize drug release from dosage forms.

The use of compendial dissolution test apparatus and techniques, such as the USP 2 (Paddle), to characterize the dissolution performance of oral drug delivery system is an established area of pharmaceutical science. However, this method is not always appropriate, particularly in dissolution tests that involves the use of very small tablets or when there is not enough drug substances available for appropriate test in the USP 2 system, particularly during the early stages of drug development.

Mini vessel systems, i.e., a small-volume dissolution apparatus, require a small drug amount and utilize a small volume of dissolving medium. Therefore, they are an emerging technology in the pharmaceutical industry that can be used to overcome the limitations associated with the USP 2-based dissolution testing method. Mini vessels offer cost effective solutions in the characterization of drug release profiles by utilizing smaller sample sizes and smaller volumes of media. Despite the industrial relevance of mini vessels only a small number of studies on mini vessel dissolution systems have appeared in the literature.

In this work, a commercially available non-compendial Minivessel Dissolution System and a USP 2 dissolution system were used to conduct dissolution tests using two different dosage forms, both containing aspirin as the Active Pharmaceutical Ingredient (API). Specifically, dissolution tests were conducted in the standard USP 2 with coated 325-mg aspirin caplets and with half doses in the USP 2 and in the Minivessel. Additionally, 81-mg enteric-coated delayed release aspirin tablets were used. Five 81-mg tablets were used in simultaneously used in dissolutions test in the USP 2 using 500 ml of dissolution medium while a single 81-mg dose and 100 ml of medium were used in the Minivessel in order to achieve similarity of surface area of tablets to volume of medium in both systems. Experiments in the USP 2 were conducted at compendial speeds of 50, 75, and 100 rpm. Minivessel experiments were conducted at different agitation speeds, i.e., 50, 75, 100, 125, 150 rpm, as well as at the agitation speeds equal to 86.2, 109.7, and 129.2 rpm since at these agitation speeds the tablet-medium mass transfer coefficients were previously predicted to be similar to those in the USP 2 at 50, 75, and 100 rpm, respectively.

The dissolution curves in the Minivessel and in the USP 2 were compared and it was found that operating the Minivessel as predicted to achieve similar mass transfer coefficients in the USP 2 produced similar dissolution curves in both systems. The comparison was additionally quantified by using the difference factor f1 and the similarity factor f2 recommended by the Food and Drug Administration (FDA).

It can be concluded that appropriately operating Minivessel can result in dissolution profiles similar to those obtained in the USP 2. The results of this work could be of significant importance to dissolution scientists in the pharmaceutical industry and help them operate mini vessels, especially during the early stages of drug development, so as to predict future dissolution profiles of the same drug product during commercialization, when the USP 2 system is routinely used.

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