Polymer–drug interacted systems in the physicochemical design of pharmaceutical dosage forms I. Drug salts with PVM/MA and with a PVM/MA hemi-ester
✍ Scribed by C. R. Willis Jr.; Gilbert S. Banker
- Publisher
- John Wiley and Sons
- Year
- 1968
- Tongue
- English
- Weight
- 510 KB
- Volume
- 57
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
The applicability of a polymer-drug interacted system in the physicochemical design of pharmaceutical dosage forms has been investigated. Salts of poly(methy1 vinyl ether/maleic anhydride) and methapyrilene base were prepared. In vitro release patterns were determined by an equilibrium dialysis procedure. Dialytic release rates of the polymer-drug salt in solution demonstrated no a preciable difference in drug availability with res ect to the free drug or its hydroc&oridt salt. In vitro dissolution rates of the pof)ymer-drug salt in solid form showed similar results. Polymer-dru salts formed with the 1,lz-dihydroxyoctadecane hemi-ester of poly-(methyl vinyf ether/maleic anhydride) exhibited rolongation of the release of the drug from granular and tabletex forms in vitro.
OLUBILIZATION of various medicinal com-S pounds by interaction with macromolecules has been extensively investigated. Such systems are usually produced by donor-acceptor mechanisms or hydrogen bonding. Unfortunately, few of these investigations have yielded products of practical value in the design of pharmaceutical dosage forms due to the low ratio of active ingredient incorporated in the system. In addition, recovery of these complexes from the reaction media is difficult or impossible in many instances.
Formation of polymer-drug salts provides a practical basis for the investigation of the physicochemical design of pharmaceutical dosage forms and subsequent biopbarmaceutic evaluations (1). Such salts have been shown to alter the biologic distribution of the drug moiety as well as prolong release when administered parenterally (2). A recent patent (3), describes a method for preparing sustained-release dosage forms by the formation of polymer-drug salts. The product is based on the interaction of a therapeutically active amine with a crosslinked copolymer containing reactive carboxyl groups. Srinivas (4) studied the reaction between car-