Stabilization of solid dispersions of nimodipine and polyethylene glycol 2000.
Previous investigations revealed that solid dispersions consisting of 20% (m/m) nimodipine and 80% (m/m) polyethylene glycol 2000 prepared by the melting method, represent supersaturated solid solutions of nimodipine recrystallizing upon storage at +25 degrees C. The objective of this study was the improvement of the storage stability by preventing recrystallization. The first approach in order to prevent recrystallization was the development of thermodynamically stable solid solutions by using solvents aiming to enhance the solubility of nimodipine in the carrier material. As potential solubility enhancing additives, polyethylene glycol 300, poly(ethylene/propylene glycol) copolymer, polypropylene glycol 1020, propylene glycol, glycerol and ethyl acetate were evaluated. The second approach enhancing storage stability was the addition of recrystallization inhibitors to supersaturated solid solutions, thereby delaying the transformation of the metastable supersaturated system to the thermodynamically stable state. Macrogol cetostearyl ether, macrogol glycerol monostearate, polysorbate 60, cetostearyl alcohol, glycerol monostearate and sodium lauryl sulphate as well as hydroxypropylcellulose, butylmethacrylat-(2-dimethylaminoethyl)methacrylat-methylmethacrylat-copolymer, polyacrylic acid, polyvinyl alcohol and povidone K17 were included in the study. It could be shown that povidone K17 effectively prevents recrystallization in solid solutions containing 20% (m/m) of nimodipine during storage at +25 degrees C over silica gel thereby ensuring a substantial increase in the dissolution rate and degree of supersaturation in water. On the contrary, stabilization by solubility enhancement was only successful at drug loadings not exceeding 1% (m/m) using polyethylene glycol 300 as solubility enhancing additive.
Institut für Pharmazeutische Technologie und Biopharmazie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany. NoraAnne.Urbanetz@uni-duesseldorf.de
Nora Anne
NA
Urbanetz
D002121:Calcium Channel Blockers / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004337:Drug Carriers; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients; D007700:Kinetics; D009553:Nimodipine / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone; D012995:Solubility; D012997:Solvents; D013535:Suspensions; D013696:Temperature; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D004337:Drug Carriers; D005079:Excipients; D012997:Solvents; D013535:Suspensions; D011092:Polyethylene Glycols; D009553:Nimodipine; D011205:Povidone