Natural micronised progesterone

Historically, the oral route of administration was not used for natural progesterone due to poor absorption and a marked first-pass effect which limited its bioavailability.8 However, it was discovered that the efficiency of oral delivery could be improved by using a micronised form of the hormone.8 Reducing particle sizes of progesterone to <10 μm increased the available surface area and improved the dissolution rate and intestinal absorption.10 Suspending NMP in oil within a gelatin capsule further improved intestinal absorption.10 In pharmacokinetic studies, physiologically relevant plasma progesterone concentrations were achieved, and remained elevated for up to 12 hours, after administration of ≥100 mg oral NMP in three divided doses.8
Development of NMP-SR followed soon thereafter. Designed on ‘EROMAT technology’, the sustained-release formulation utilizes a hydrophilic matrix polymer which releases micron-sized particles of progesterone in a controlled manner over 16 to 24 hours. This gradual release of progesterone, together with a prolonged elimination half-life of 18 hours11 and high protein binding (90−99%), maintains serum progesterone concentrations in the luteal phase range (i.e. ≥ 14 ng/mL) with once-daily dosing.9 After 7 daily doses of NMP-SR 200, 300, or 400 mg, mean mid-luteal serum progesterone concentrations of 20.6, 36.1 and 46.2 ng/mL, respectively, were measured.9,12 The controlled release of drug particles during intestinal transit facilitates lymphatic absorption of intact drug into the systemic circulation from the small intestine and direct entry of the drug into the systemic circulation via the mucosal lining of the colon. By circumventing first-pass metabolism, active circulating drug elicits the desired therapeutic effect while minimizing the risk of metabolite-related adverse effects.9 In this manner, NMP-SR overcomes the limitations of conventional oral NMP.