Study on emulsifier screening and in vitro release of a compoundconjugated estrogens progesterone cream for vaginal use
Objective To screen the emulsifiers of compounded conjugated estrogens progesterone cream for vaginal use and to determine the in vitro release characteristics of the cream.Methods Cetyl alcohol,glyceryl monostearate,white beeswax,methyl stearate,liquid paraffin,cetearyl stearate,propylene gly-col stearate and progesterone were used as oil phase and benzyl alcohol,glycerol,conjugated estrogens and purified water as aqueous phase.2 O/W complexes of conjugated estrogens(CE)progesterone(P4)vagi-nal creams were prepared by emulsification method,and the quality was evaluated by a composite scoring method.16 New Zealand lop-eared rabbits were randomly divided into 4 groups:SDS group(SDS-contai-ning cream was administered),Tefose® 63 group(Tefose® 63-containing cream was administered),blank substrate group(blank substrate without emulsifier)and saline group(saline was administered instead of cream).All 4 groups were administered 0.5 mL of the cream on the skin,and 1 mL of the cream was ad-ministered vaginally once a day,and the irritation properties of the creams were evaluated by taking the skin and vagina tissues after 7 consecutive days and conducting HE staining.The superior compounded cream was selected,and the cumulative release per unit area and cumulative release rate of CE and P4 from the compounded cream were determined using LOGAN in vitro transdermal instrument.Result The com-posite score of SDS-containing cream was(95.83±0.03)points and the composite score of Tefose® 63-containing cream was(95.80±0.05)points.The vaginal mucosa was intact in rabbits in the blank matrix and saline groups,significant flat epithelial damage to the vaginal mucosal complex was seen in SDS group,and slight damage to the vaginal mucosa was seen in the Tefose® 63 group.Neither of the 2 creams with different emulsifiers showed significant skin irritation.The release rate of CE in the optimal com-pounded cream for vaginal use was screened to be(13.15±0.37)μg·cm-2·h-1/2,and that of P4 was(297.73±12.48)μg·cm-2·h-1/2,and the cumulative release per unit area of both of them showed a lin-ear relationship with the square root of time,which was in accordance with the Higuchi equation.Conclu-sion The compounded conjugated estrogens progesterone vaginal cream using Tefose® 63 as the emulsifi-er was white and delicate in appearance,stable in nature,less irritating to the vaginal mucosa,and ithad good in vitro release characteristics.
万方数据
维普
