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.