Norethisterone-cholesterol eutectic mixture as an oral sustained-release hormonal preparation: bioequivalence study...

A solid dispersion of norethisterone and cholesterol (NET:CHOL; eutectic 1:4 w/w) was prepared by melting and rapid cooling. The fused material was then mixed with lactose as vehicle. Soft gelatin capsules were filled with 55 mg of the final mixture to give 0.35 mg of NET. One control formulation prepared with fused NET and lactose (NET:LAC) was capsuled with the same NET dosage, and one commercial tablet (Dianor, Syntex) with 0.35 mg NET were used as reference formulations. In a cross-over study, five female volunteers received, one month apart, in fasting state, each one of the three formulations. Blood samples were drawn at O,O.5,1,1.5,2,4,8,12,24 and 36 hours after dosing. Immunoreactive plasma NET was measured by RIA to assess pharmacokinetic parameters. The NET:CHOL formulation showed a greater area under the serum concentration-time curve, lower peak concentrations and a smaller release rate constant as compared to the reference preparations. It is concluded that the NET:CHOL eutectic mixture is a modified release dosage form and a sound approach in regulating the drug access rate to the body's central compartment.