Microencapsulation of hydrophilic drug substances using biodegradable polyesters. Part I: evaluation of different techniques for the encapsulation of pamidronate di-sodium salt.

ABSTRACT

The preparation of microparticles (MP) with a high loading of hydrophilic, low molecular weight drugs is an ambitious goal. This study investigated the microencapsulation of a bisphosphonate salt (BP) into a biodegradable star branched terpolymer Poly(D,L-lactide-co-glycolide-D-glucose) (PLG-GLU). Two aqueous solvent evaporation microencapsulation-techniques were studied, namely the water-in-oil-in-water-technique (WOW) and the solid-in-oil-in-water-technique (SOW) as well as a non-aqueous microencapsulation method based on suspension of the drug in organic solvents (SOO). The aqueous microencapsulation techniques showed several disadvantages, which rendered it difficult to prepare MP with high drug loading (approximately 30% w/w). A modified SOO-technique allowed the preparation of highly loaded MP up to 28% (w/w). A micronized drug substance and a polymer solvent system consisting of equal volumes of acetonitrile (ACN) and dichloromethane (DCM) were essential features of the SOO-process. A morphologic examination of the internal structure by confocal laser scanning microscopy demonstrated that these MP contain many vacuoles and pores, leading to an unfavourable initial burst release of APD. This process needs further optimization with respect to drug release and may then be of general interest for the preparation of highly-loaded MP with other drug salts and hydrophilic macromolecules.