Date of Award

6-2012

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Spiro Spireas, PhD

Second Advisor

Ruth D Thornton, PhD

Third Advisor

David Cavanaugh, BS

Abstract

Simvastatin is a well known anti-cholesterol drug that is commercially available in the United States in various strengths including Simvastatin Tablets, USP 80 mg, that are under the brand name Zocor (manufactured by Merck Pharmaceutical Co.) and various generic equivalent products for example those manufactured by Teva Pharmaceuticals, Inc. and Dr. Reddy’s Laboratories, Ltd. When generic products are tested in the United States, they must be found to be equivalent with their branded products by the FDA. Therefore, generic Simvastatin Tablets, USP 80 mg, have been tested and approved by the FDA as equivalents to, and substitutable with, the branded Zocor tablets of the same strength. The Teva and Reddy’s generic Simvastatin products have also been found to be bioequivalent to the branded Zocor product in FDA-approved in-vivo clinical studies involving healthy human subjects (dosed under fasting and nonfasting conditions).

In this study, the drug dissolution profiles of the brand Zocor and the generic Teva and Reddy’s Simvastatin 80 mg tablets were assessed and compared using twelve different in-vitro dissolution tests consisting of three different dissolution media (i.e., three aqueous solutions of 0.5% w/v SLS in Phosphate Buffer pH 7.0, Purified Water, or Acetate Buffer pH 4.5, respectively), two different volumes of dissolution medium (i.e., 500 or 900 mL per dissolution vessel), and two different agitation speeds (i.e., paddles rotating at 35 or 50 rpm). The 10-min, 20-min and 30-min drug dissolution rates of each of the two generic products were statistically compared to those of the reference Zocor product using a t-test to evaluate similarities or significant differences between the compared drug dissolution rates of the Teva vs. Zocor and Reddy’s vs. Zocor product pairs under evaluation.

It was established in this study that two dissolution tests in particular possess promising in-vitro/in-vivo correlation characteristics, which should be further evaluated. Specifically, it was found that two dissolution tests consisting of 900 mL (per vessel) of an aqueous dissolution medium comprising of 0.5% w/v SLS in either Phosphate Buffer pH 7.0 or Acetate Buffer pH 4.5, maintained at 37oC and agitated via paddles rotating at a speed of 35 rpm, have produced statistically similar 10-min, 20-min and 30-min drug dissolution rates displayed by all three products. These results show that the use of these two in-vitro dissolution tests may have reliable predictive in-vivo power, thereby possibly facilitating the timely and cost-efficient development of new generic immediate-release Simvastatin products that would be bioequivalent to their branded Zocor counterpart.

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