Date of Award


Document Type


Degree Name

Doctor of Philosophy (Ph.D.)



First Advisor

Donald Y. Barker

First Committee Member

Ivan E. Rowland

Second Committee Member

Charles W. Roscoe

Third Committee Member

John K. Brown

Fourth Committee Member

Carl C. Riedesel


An in vitro method was tested whereby the processes of dissolution and distribution of active ingredient into a lipoid solvent were combined in one model and evaluated.

The objectives of this research project were: (1) to evaluate the efficacy of the in vitro model known as the Desaga Resomat, in the testing of gastrointestinal absorption; (2) to apply the procedure and instrument to a group of therapeutically important products in determining their absorption characteristics; (3) to graphically illustrate the absorption profile of a specific drug as per cent absorbed vs. time, simulating in vivo absorption; (4) to compare the profile data with experimentally determined dissolution studies; (5) to relate, biopharmaceutically the application of the profile data to absorption characteristics.

A literature survey was performed including the history of dissolution rate methodology and its influence on the bioavailability of medication from the dosage form.

A discussion of tile experimental procedure was presented including the graphical illustration of tile resorption profiles for the three commonly known drugs used in the verification of the apparatus.

The method was applied to a group of therapeutically important products, specifically, thiazide diuretics as well as non-thiazide diuretics such as Spironolactone, Acetazolamide, Ethacrynic Acid, Chlorthalidone, and Furosemide.

Dissolution properties for each drug were determined using the Desaga Resomat as well as the '"Beaker Method" of Levy and Hayes. The method used in this work involved the use of a glass model apparatus which showed the basic physical and chemical principles of the absorption process, namely, the solubility of a drug in the aqueous phase and its distribution into a lipoid phase. The dosage form was placed into an aqueous buffered solution. The pH of the buffered solution was adjusted so as to correspond to the pH of the gastro-enteral system. As a result of pressure changes corresponding to peristalsis the dissolved drug passed through a sinter and was then subjected to distribution, with a suitable lipoid solvent. The absorption profiles were determined by measuring, spectrophotometrically, the concentration of the drug in the lipoid phase. Graphical displays were constructed representing the solubility and distribution of the drug at specific pH-time-intervals.





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