Injectable polyanhydride granules provide controlled release of water‐soluble drugs with a reduced initial burst

A method for preparing polyanhydride granules of an injectable size was developed. The resulting granules permitted a nearly constant release of low‐molecular‐weight, water‐soluble drugs without an initial burst. The polyanhydrides used were poly(fatty acid dimer), poly(sebacic acid), and their copolymers. The dyes acid orange 63 and p‐nitroaniline were used as model compounds for drugs. Polymer degradation and drug release for disks and variously sized granules of copolymers containing drugs, prepared by a water‐in‐oil (W/O) emulsion method, were compared with those for devices prepared by the usual compression method. In the W/O emulsion method, a mixture of aqueous drug solution and polymer—chloroform solution was emulsified by probe sonication to prepare a very fine W/O emusion. The powder obtained by freeze‐drying of the W/O emulsion was pressed into circular disks. In the compression method, the drug was mechanically mixed with the polymer, and the mixture was compressed into circular disks. The resulting disks were ground to prepare granules of different sizes. The granules encapsulated more than 95% of the drug, irrespective of the preparation method. Both methods were effective in preparing polymer disks capable of controlled drug release without any initial burst. However, as the granule size decreased to an injectable size (diameter, < 150 μm), a large difference in the drug release profile was observed between the two preparation methods. The injectable granules obtained by the W/O emulsion method showed nearly constant drug release without any large initial burst, in contrast to those prepared by the compression method, irrespective of the drug type. Degradation studies of the granules demonstrated to difference in the degradation profile of the granule matrix itself between the two methods. Light microscopic observations of polymer disk prepared by the compression method indicated a nonuniform distribution of dye islands throughout the matrix. In contrast, a highly homogeneous mixing of dye and polymer was achieved for devices prepared by the W/O emulsion method. It is therefore possible that this highly uniform distribution of drug throughout the polymer matrix leads to a reduced initial burst in drug release from the injectable granules obtained by the W/O emulsion method.