A NEW APPROACH TO THE DEVELOPMENT OF SUSTAINED ACTION DOSAGE FORMS II. INTERACTIONS OF DRUGS WITH POLYMERS PRECIPITATED FROM NON-AQUEOUS SOLVENTS
Abstract
Recent advances in pharmaceutical development have resulted not only in new and improved therapeutic agents, but also in unique and greatly refined systems for maintaining and administering the therapeutic agents. The sustained release dosage form was developed within the past decade or so and the interest generated by this development has led to extensive investigation in the area of prolonged or extended duration of action. This study was prompted by the fact that currently available sustained release products are produced, for the most part, by intricate and complex production procedures resulting in products costly in nature and possessing greater than the desired variability between dosage units. To overcome these shortcomings, it was our intent to prepare reproducible physical chemical complexes of selected drugs and polymeric materials. Several commercially available polymeric materials representing various resin classifications were screened for their potential usefulness in sustained release applications. Since no acceptable polymer was found, a derivative of one of the previously screened polymers (SMA 1000A methyl half-ester) was prepared and found potentially useful. Using this polymer derivative, a satisfactory assay procedure based on the construction correction method was developed for the assay of methantheline bromide (the drug used in this study) in the presence of the polymeric material. Interacted systems of SMA 1000A methyl half-ester and methantheline bromide were prepared by adding a methanol solution of the polymer to the drug dissolved in 0.2N hydrochloric acid. During the course of this phase of the study the concentration of the polymer solution was maintained constant at 20% while the drug solution was controlled over a 3% to 15% range. The final complex was isolated as a precipitate in the aqueous media and the amount of drug associated with the polymer was found to be a function of the initial drug concentration in the acid. Preparation of several similarly prepared batches indicated that the interaction procedure was highly reproduced. The in vitro evaluation was conducted using the rotating bottle method and a gradually increasing pH. These procedures demonstrated the batch to batch reproducibility of the in vitro release rates of the prepared complexes and indicated a potential usefulness of the products for sustained release preparations. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmacology
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