Increased dissolution and physical stability of micronized nifedipine particles encapsulated with a biocompatible polymer and surfactants in a wet ball milling process.
Suspensions of nifedipine, a practically water-insoluble drug, were prepared in the presence of a biocompatible polymer, polyvinylpyrrolidone (PVP, K value 17), and three surfactants, sodium lauryl sulfate (SLS, anionic), cetyltrimethylammonium bromide (CETAB, cationic), polysorbate 80 (Tween 80, nonionic), by wet milling in ceramic ball mills. Nifedipine powders encapsulated with PVP and the surfactants were recovered from the suspensions after milling and evaluated for changes in particle size, morphology, sedimentation rate in aqueous suspensions, crystal form, and dissolution. Particle size analysis indicated that milling of suspensions in solutions of PVP and surfactants is an efficient method for reducing the particle size of nifedipine to below 10 microm. Furthermore, DSC and XPS analysis indicated that during milling the nifedipine crystals were coated with the PVP or surfactants and that milling with PVP stabilized the nifedipine crystal form during milling while nifedipine was gradually amorphisized when milled in a quaternary nifedipine/PVP/SLS/CETAB system. The decrease in particle size caused a significant decrease in sedimentation rate and increased the dissolution rate of nifedipine in simulated gastric fluid when compared to milled nifedipine and powder mixtures of the drug and the excipients.
Li
Ning
N
College of Pharmacy, University of Louisiana at Monroe, USA.
DeGennaro
M D
MD
Liebenberg
W
W
Tiedt
L R
LR
Zahr
A S
AS
Zahn
A S
AS
Pishko
M V
MV
de Villiers
M M
MM
D001672:Biocompatible Materials; D002121:Calcium Channel Blockers / Q000737:chemistry*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D009543:Nifedipine / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers; D011136:Polysorbates; D012967:Sodium Dodecyl Sulfate; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents; D013535:Suspensions
D001672:Biocompatible Materials; D002121:Calcium Channel Blockers; D002593:Cetrimonium Compounds; D005079:Excipients; D011108:Polymers; D011136:Polysorbates; D013501:Surface-Active Agents; D013535:Suspensions; D012967:Sodium Dodecyl Sulfate; D009543:Nifedipine; D000077286:Cetrimonium