Pharmacokinetics and Correlation Between in Vivo and in Vitro Transdermal Penetration of Indomethacin Submicron Emulsion Gel

OBJECTIVE To study the pharmacokinetics of indomethacin(IMC) submicron emulsion gel in rabbits and evaluate its bioavailability and correlation between in vivo and in vitro transdermal penetration. METHODS A modified Franz diffusion cell method was used to test the transdermal penetration of IMC submicron emulsion gel on SD rat abdominal skin. A single dose of 10 g (equivalent to IMC 100 mg) submicron emulsion gel or commercial IMC cream was laid on abdominal skin of rabbit on both sides for an area of 40 cm². Blood samples were collected from heart at predetermined time points and plasma concentration was determined by HPLC-UV. Deconvolution method was used to study the correlation between in vitro transdermal penetration data and in vivo pharmacokinetic data. RESULTS The cumulative transdermal permeation amount of IMC submicron emulsion gel in vitro for 24 h was twice that of the commercial IMC cream. Compared with the commercial IMC cream, the T_max, C_max, T_1/2 had no significant differences, the AUC_0-24 and AUC_0-∞ of IMC submicron emulsion gel was about twice that of the commercial indomethacin cream. The in vitro and in vivo correlation coefficient of IMC submicron emulsion gel was 0.930. CONCLUSION Compared with the commercial IMC cream, IMC submicron emulsion gel can increase the amount of IMC penetrated into blood, improve the bioavailability of IMC, and the correlation between in vivo and in vitro transdermal penetration is good.