Low molecular weight PLA: a suitable polymer for pulmonary administered microparticles?
Beclomethasonedipropionate (BDP)-containing microparticles were prepared 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 and 15,000 were used as matrix polymers. In all experiments the mean diameter of the microparticles was 1-5 microns with a drug content > or = 23 per cent. Microparticles of PLA, MW 2000, showed a prolonged and complete release over 8 h, whereas those of PLGA liberated only 20 per cent of the encapsulated drug within 8 h. BDP was determined by a validated reversed-phase HPLC method with a detection limit of 20 ng/ml. The encapsulated steroid seemed to be dissolved within the polymer, as differential scanning calorimetry suggested. Considering mean particle size, drug load, release characteristics and the status of the drug inside the matrix, the dosage form showed very good characteristics 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 strong deterioration of microparticles, main structures were still visible by SEM after an incubation of 36 h in diluted bronchial fluid ex vivo. Degradation in phosphate buffered saline, protein solution and even in port liver esterase suspension resulted in minor effects on the particle surface.
Institut für Pharmazeutische Chemie, Westfälischen Wilhelms-Universität, Münster, Germany.
B
B
Wichert
P
P
Rohdewald
D000280:Administration, Inhalation; D000818:Animals; D001507:Beclomethasone / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004950:Esterases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007773:Lactates / Q000737:chemistry*; D019344:Lactic Acid; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008854:Microscopy, Electron; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013552:Swine
D003692:Delayed-Action Preparations; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D004950:Esterases; D001507:Beclomethasone