DEVELOPMENT OF CONTROLLED GASTRIC RETENTION DRUG DELIVERY SYSTEMS AND A ROTARY VACUUM IMMERSION COATING DEVICE
Abstract
The evaluation of the bioavailability of tetracycline administered from experimental uncoated and gastric retention coated tablets, compared with a commercial capsule product, was undertaken in man. The bioavailability of tetracycline from all the dosage forms was the same within statistical limits. The failure of the gastric retention system to enhance the availability of tetracycline was attributed to unreliable swelling or rupturing of the retention film which resulted in premature gastric emptying. A series of gastric retention film compositions were studied for their swelling and release characteristics. The film system was modified from the standard composition of PVM/MA-169:Tween 20:Triacetin (8:0.56:4 parts by weight) in a mixed solvent system of ethyl acetate and acetone by varying the polymer molecular weight, the anhydride content of the polymer, the type and level of surfactant, the type and level of plasticizer, and the solvent system. It was determined that certain film constituents and fixed concentration ranges of these constitutents were necessary to achieve satisfactory film swelling and controlled release. The standard gastric retention film system was applied to various tablet substrates. Rapid swelling and complete distention of the film into the retention sac was observed when the film was applied to substrates containing an alkaline buffer (tris) and a gas generating material (sodium bicarbonate). These delivery systems however, showed no prolongation of gastric retention times when compared to enteric coated tablets. This was attributed to the deleterious effects of high pH and pressure on the retention film itself, as well as possibly pH and pressure effects in the stomach, to increase gastric motility and emptying. The overall finding of these film and substrate modification studies was that the controlled gastric retention drug delivery unit, made up the film and the tablet substrate, is a complex system. Factors which promote rapid swelling or desired drug release properties are the same factors which increase the possibilities of film rupture and gastric emptying. A new tablet delivery system was developed in which the film was used only for gastric retention, while drug release was controlled by a matrix or dosing core. The retention film was applied as an incomplete coating to an insoluble anchoring material, which was part of either a layer or off-center compression coated tablet, leaving the dosing layer or core uncoated and exposed to release drug without film control. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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