Date of Award

1991

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmaceutical Sciences

College

College of Graduate Studies

First Advisor

J. David McCallister

Second Advisor

Paul J. Niebergall

Third Advisor

James E. Wynn

Fourth Advisor

Julian E. McGill

Fifth Advisor

Edward D.Sumner

Sixth Advisor

Farid Sadik

Abstract

The purpose of this research was to evaluate the effect of the poorly soluble diluents; calcium sulfate dihydrate, dibasic calcium phosphate dihydrate, and tribasic calcium phosphate on medicament release from solid dosage forms. Initial findings led to an investigation of the use of these diluents as matrix forming agents in the formulation of sustained release solid dosage farms. An existing single station tablet press was instrumented with a transducer strain gauge apparatus to monitor compression force applied during tablet manufacture. An automated dissolution system was used to determine medicament release from the dosage forms under investigation. These three diluents when directly compressed with drug had shown matrix forming abilities in media of pH 4.0 to 7.5. However, they do not exhibit these same abilities in O.1N HCl. The addition of Carbopol 934P (1-5%) provided a gel-like protective barrier in O.1N HCl and acacia assisted in maintaining the matrix structure in this acidic environment. In addition, medicament release appeared nearly constant over eight to ten hours. The tablets were manufactured by weighing the excipients, screening to eliminate agglomerates, blending, and compressing. Acetaminophen was chosen as model drug due to its relatively pH independent solubility profile over the range of interest. However, the system also showed the ability to sustain the release of theophylline and chlorpheniramine maleate. Results indicate promise for the use of these calcium diluents as matrix forming agents in the formulation of sustained release solid dosage forms. Medicament release can be controlled by adjustment of formulation variables and this simple process appears unaffected by several processing variables. The simplicity, novelty, and applicability of this method of achieving sustained release of medicament from solid dosage forms warrants additional investigation of its use in the formulation of pharmaceutical products.

Rights

All rights reserved. Copyright is held by the author.

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