Sustained release microspheres of metoclopramide using poly(D,L-lactide-co-glycolide) copolymers.
Metoclopramide was encapsulated with poly(D,L-lactide co glycolide) copolymers of different molecular weights using the emulsification/solvent evaporation technique. These polymers included poly(D,L-lactide-co-glycolide) 50:50 with inherent viscosity (i.v.) 0.2, and average molecular weight 8000, poly(D,L-lactide-co-glycolide) 50:50 with i.v. 0.8 and average molecular weight 98000 and poly(D,L-lactide-co-glycolide) 85:15 with i.v. 1.4 and average molecular weight 220000. The effect of the polymers' molecular weights as well as the polymer-to-drug ratios on the yield, the particle size distribution, and the drug content of the microspheres was investigated. The release rate of the drug was studied for 96 h in a phosphate buffer of pH 7.4. The study also investigated the effect of the new poly(lactide-co-glycolide)-H series on the characteristics of the prepared microspheres. Data revealed that a higher yield was obtained with polymers of lower molecular weights. A lower yield was also obtained with increasing the drug-to-polymer ratios for all the investigated polymers. The drug content of the microspheres was lower than expected, ranging from 49-85%, which suggested a chemical interaction between the drug and the polymers, as proved by differential scanning calorimetry (DSC) and infra red (IR) studies. A higher interaction was obtained with the H-series of the copolymers. The release of the drug mainly followed zero order kinetics on increasing either the polymers' molecular weights or the polymer-to-drug ratios. Diffusion kinetics was observed only with those batches prepared with low polymer-to-drug ratios. The release rate was a function of both the polymers' molecular weights and the drug-to-polymer ratios.
Elkheshen
S A
SA
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. selkshen@ksu.edu.sa
Radwan
M A
MA
D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics; D002214:Capsules; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry; D008787:Metoclopramide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry
D000932:Antiemetics; D002214:Capsules; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008787:Metoclopramide