Long-acting contraceptive agents: the influence of pharmaceutical formulation upon biological activity of esters of norethisterone.
17 beta-esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) have been formulated as aqueous microcrystalline suspensions and oily solutions for administration to rats to assess the length of progestogenic activity. Results show that, for some of the esters, the rate-controlling step in prolonging activity is the rate of drug release from the injected formulation. For these esters, when formulated as suspensions, it is proposed that crystal size and form will have a critical effect upon duration of estrus suppression. The influence of crystal form has been demonstrated with the 4-(butoxy)phenylacetate ester for which two different crystal forms have been identified. The lower melting point, more soluble crystal form shows marked prolongation of action, whereas the other form is ineffective.
D002151:Calorimetry; D003692:Delayed-Action Preparations; D004952:Esters; D009640:Norethindrone / Q000031:analogs & derivatives*; D012995:Solubility; D013329:Structure-Activity Relationship
D003692:Delayed-Action Preparations; D004952:Esters; D009640:Norethindrone