Positively charged self-emulsifying oil formulation for improving oral bioavailability of progesterone.
A self-emulsifying oil formulation (SEOF) comprised of Tween 80, benzyl alcohol (BA), ethyl oleate (EO), and oleylamine (OA), able to produce positively charged submicron emulsions upon aqueous or buffer dilution, was developed and characterized. The positive charge of the formulation was attributed to the localization of the cationic lipid, OA, at the oil/water interface of the diluted SEOFs. Binary phase diagram analysis of the basic lipophilic system showed that the SEOF elicited progressive inverse phase behavior under continuous aqueous phase dilution. At infinite dilution fine submicron o/w emulsions were formed only when BA concentrations did not exceed 50% in the formulation. The self-emulsification process was not markedly affected by the variation in pH over the entire physiological range. The neurotoxic effects observed in acute toxicity studies with the concentrated emulsion containing 3% BA obtained from the dilution of the SEOF vehicle were attributed to the BA since a simple aqueous solution at the same BA dose caused similar adverse effects. However, no toxic effects were noticed when the dose administered was 30 times the potential dose that could probably be administered to humans. Comparative oral bioavailability studies in young female rats using several different liquid dosage forms of progesterone indicated that of those studied, only the positively charged SEOF could be considered a potential effective dosage form for oral administration of progesterone since it elicited the highest and most satisfactory absorption profile.
Gershanik
T
T
Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Benita
S
S
D000818:Animals; D001682:Biological Availability; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients; D005260:Female; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D009821:Oils; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats
D004655:Emulsions; D005079:Excipients; D009821:Oils; D011374:Progesterone