Development of poly(ortho esters) and their application for bovine serum albumin and bupivacaine delivery

Abstract

The preparation of drug delivery devices using solventless fabrication procedures is of significant interest and two such procedures are described. In one such procedure, powdered polymer and micronized protein are intimately mixed and then extruded into 1 mm strands that are cut to the desired length. The polymers used were specifically designed to allow extrusion at temperatures where proteins maintain activity in the dry state. In vitro erosion and BSA release show that BSA release and polymer erosion occur concomitantly indicating an erosion-controlled process. There is a lag-time, but that can be eliminated by the addition to the mixture prior to extrusion small amounts of poly(ethylene glycol) or its methoxy derivatives. The lag-time could also be eliminated by using an AB-block copolymer where A is poly(ortho ester) and B is poly(ethylene glycol). Another means of using solventless fabrication methods is to use a semi-solid material into which drugs can be mixed at room temperature and the semi-solid injected. Data on BSA and bupivacaine release are presented.