Multi-unit controlled release systems of nifedipine and nifedipine:pluronic F-68 solid dispersions: characterization of release mechanisms.
Nifedipine (N) and nifedipine. Pluronic F-68 solid dispersion (SD) pellets were developed and characterizedfor drug release mechanisms from a multi-unit erosion matrix system for controlled release. Nifedipine was micronized using a jet mill. Solid dispersion with Pluronic F-68 was prepared by the fusion method. Nifedipine and SD were characterized by particle size analysis, solubility, differential scanning calorimetry (DSC), and x-ray diffraction (XRD) studies. Samples were subsequently processed into matrix pellets by extrusion/spheronization using Eudragit L 100-55 and Eudragit S 100 as release rate-controlling polymers. Drug release mechanisms from pellets were characterized by microscopy and mercury intrusion porosimetry; DSC and XRD studies indicated no polymorphic changes in N after micronization and also confirmed the formation of SD of N with Pluronic F-68. Pellets of N showed a 24-hr drug release profile following zero-order kinetics. Pellets of SD showed a 12-hr release profile followingfirst-order kinetics. Aqueous solubility of N after SD formation was found to be increased 10-fold. Due to increased solubility of N in SD, the drug release mechanism from the multi-unit erosion matrix changed from pure surface erosion to an erosion/diffusion mechanism, thereby altering the release rate and kinetics.
Mehta
Ketan A
KA
Rohm Pharma Polymers, Degussa Corporation, Piscataway, New Jersey 08855, USA.
Kislalioglu
M Serpil
MS
Phuapradit
Wantanee
W
Malick
A Waseem
AW
Shah
Navnit H
NH
D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D009543:Nifedipine / Q000737:chemistry* / Q000493:pharmacokinetics; D020442:Poloxamer / Q000737:chemistry* / Q000493:pharmacokinetics; D016062:Porosity / Q000187:drug effects
D002214:Capsules; D003692:Delayed-Action Preparations; D020442:Poloxamer; D009543:Nifedipine