Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or solutol HS-15.
The objective of our study was to find mechanisms responsible for solubility enhancement of nifedipine in solid dispersions of vitamin E TPGS and/or solutol HS-15. Solid dispersions of nifedipine with selected polymers such as vitamin E TPGS, solutol HS-15, PEG(1,000), and lipocol C-10 of varying drug/polymer ratios were prepared by a fusion method. The solubility enhancement was found to be in the order of vitamin E TPGS > solutol HS-15 > lipocol C-10 > PEG(1,000). Lipocol C-10, with a similar hydrophilic-lipophilic value as vitamin E TPGS, showed a comparable retained solubility enhancement during saturation solubility studies but had lower dissolution profile. Overall, vitamin E TPGS showed the best solubility and dissolution performance, while solutol HS-15 and lipocol C-10 demonstrated moderate solubility enhancements. Solid dispersions of vitamin E TPGS as prepared by microfluidization technique initially showed slightly higher solubility compared with samples prepared by fusion method, but eventually it became the same as the study progressed. However, solid dispersion of solutol HS-15 as prepared by microfluidization demonstrated a significant, sustained increased in solubility over its sample when prepared by fusion method. Based on these results, we concluded that enhanced solubility using vitamin E TPGS and solutol HS-15 resulted from a partial conversion of crystalline drug to the amorphous form, increase in wettability of the drug by water soluble polymers, better separation of drug particles, micellar solubilization of drug by high concentrations of surfactant polymers, and interaction between polymer and drug at the molecular level.
Department of Biomedical & Pharmaceutical Sciences, School of Pharmacy, University of Rhode Island, Kingston, 02881, USA.
Minal
M
Rajebahadur
Hossein
H
Zia
Anthony
A
Nues
Chong
C
Lee
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008823:Micelles; D009543:Nifedipine / Q000008:administration & dosage* / Q000737:chemistry; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry; D017155:Wettability; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D008823:Micelles; D013229:Stearic Acids; D014810:Vitamin E; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D009543:Nifedipine; C014225:tocophersolan