Development and Characterization of Lyophilized Diazepam-Loaded Polymeric Micelles

作者：Suksiriworapong Jiraphong^*; Rungvimolsin Tana****; A gomol Atitaya; Junyaprasert Vara**** Buraphacheep; Chantasart Doungdaw

来源：AAPS PHARMSCITECH, 2014, 15(1): 52-64.

DOI：10.1208/s12249-013-0032-4

• diazepam
• lyophilization
• poloxamer 407
• polymeric micelles
• D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)

Polymeric micelles were studied as delivery carriers of diazepam, a practically insoluble drug in water, for rectal administration. The diazepam-loaded polymeric micelles were developed by using poloxamer 407 (P407), poloxamer 188, and D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS). Among the used polymers, TPGS resulted in polymeric micelles with good characteristics for encapsulation of diazepam which had the small particle size of 8-12 nm and narrow size distribution (PI 0.053-0.275). Additionally, 7.5% w/v of TPGS could entirely entrap the desired concentration of diazepam (5 mg/mL). To improve the physical stability upon lyophilization, an addition of P407 of 1% w/v prevented aggregation, increased physical stability, and maintained chemical stability of the lyophilized powders of diazepam-loaded polymeric micelles for 3 months storage at 4 C. The rate and amount of diazepam release from TPGS polymeric micelles mainly depended on the concentration of TPGS. The release data were fitted to Higuchi%26apos;s model suggesting that the drug release mechanism was controlled by Fickian diffusion. In conclusion, 10% w/v TPGS and 1% w/v P407 were the optimum formulation of lyophilized diazepam-loaded polymeric micelles.

• 出版日期2014-2