Stability of forskolin in lipid emulsions and oil/water partition coefficients

Article abstract of DOI:10.1248/cpb.39.1032

Forskolin (FK), a diterpenoid isolated from Coleus Forskohlii, underwent base-catalyzed hydrolysis, producing 7-deacetyl forskolin. The half-life at pH 7.0 and 25°C was 16 d. Because of its poor solubility in water and degradation, the drug was incorporated in lipid emulsions (soybean oil/water=10.9/89.1 v/v, average diameter of the droplets, 204 nm). No degradation of the drug was found in the lipid emulsion up to 30 d. The distribution of FK in the lipid emulsions was investigated based on a three-phase model which assumes that the drug resides in the oil and water phases and at the oil/water interface. From the determination of bulk oil/water and lipid emulsion partition coefficients, the relative percentages of the drug in the oil droplets, in the aqueous phase and at the interface were 43.3, 4.9 and 51.3%, respectively. This distribution profile seems to be consistent with the improved stability of FK in the lipid emulsions where the drug residing in the oil phase and at the interface is well protected from hydrolysis. The FK lipid emulsions should be given more interest in access to preclinical and clinical tests because the drug was well stabilized in the formulation and the excipients used are acceptable to human subjects.