Design and evaluation of an emulsion vehicle for paclitaxel. II. Suppression of the crystallization of paclitaxel by freeze-drying technique.
Although paclitaxel is soluble in vitamin E up to 40 mg per g, crystallization was detected at loadings higher than 15 mg per g. Water appeared to be an important factor causing the observed crystallization, and therefore, a freeze-drying technique was investigated to produce reconstitutible vitamin E emulsions, to increase drug loading without crystal formation after reconstitution. The emulsion was freeze-dried using a laboratory freeze-drier and the droplet size was measured using dynamic light scattering. The freeze-dried emulsions using sucrose as a cryoprotectant could be easily reconstituted. The loading of paclitaxel in the freeze-dried emulsions could be increased to 25 mg per g of vitamin E without crystal formation, and the mean emulsion droplet size remained smaller than 0.2 mum over 430 days (4 +/- 2 degrees C). The previously observed surfactant-enhanced crystallization could also be suppressed using the freeze-drying technique.
Han
Jihong
J
School of Pharmacy, and Institute for Science and Technology in Medicine, Keele University, Staffordshire, UK. jihong.han@gmail.com
Washington
Clive
C
Davis
Stanley S
SS
D003451:Cryoprotective Agents / Q000494:pharmacology; D003460:Crystallization; D004655:Emulsions; D005612:Freeze Drying / Q000379:methods*; D005947:Glucose / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D020442:Poloxamer / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D014199:Trehalose / Q000494:pharmacology
D003451:Cryoprotective Agents; D004655:Emulsions; D014677:Pharmaceutical Vehicles; D020442:Poloxamer; D013395:Sucrose; D014199:Trehalose; D005947:Glucose; D017239:Paclitaxel