LOW-MOLECULAR-WEIGHT PLA - A SUITABLE POLYMER FOR PULMONARY ADMINISTERED MICROPARTICLES

Beclomethasonedipropionate (BDP)-containing microparticles were prepar ed by the solvent evaporation/extraction method. Different preparation parameters were optimized before investigations. Polylactic acid (PLA ) and polylactic/glycolic acid (PLGA) with molecular weights of 2000 a nd 15 000 were used as matrix polymers. In all experiments the mean di ameter of the microparticles was 1-5 mum with a drug content greater-t han-or-equal-to 23 per cent. Microparticles of PLA, MW 2000, showed a prolonged and complete release over 8 h, whereas those of PLGA liberat ed only 20 per cent of the encapsulated drug within 8 h. BDP was deter mined by a validated reversed-phase HPLC method with a detection limit of 20 ng/ml. The encapsulated steroid seemed to be dissolved within t he polymer, as differential scanning calorimetry suggested. Considerin g mean particle size, drug load, release characteristics and the statu s of the drug inside the matrix, the dosage form showed very good char acteristics for inhalatory application. Surface characteristics of the microparticles were visualized by scanning electron microscopy (SEM). Although in vitro studies with human bronchial fluid resulted in a st rong deterioration of microparticles, main structures were still visib le by SEM after an incubation of 36 h in diluted bronchial fluid ex vi vo. Degradation in phosphate buffered saline, protein solution and eve n in port liver esterase suspension resulted in minor effects on the p article surface.