No abstract

Microemulsions are thermodynamically stable, transparent, isotropic systems, consisting of oil, water and surfactant with or without a cosurfactant. They are considered ideal for drug delivery due to their low viscosity, ease of preparation, improved drug stability and solubility, small droplet size, surfactant provoked permeability and protection against enzymatic degradation.1) The later characteristics are responsible for improved permeability of the drug across biological membranes including the skin. Although the oil and surfactant constituents are known to enhance the solubility of lipophilic drugs, at higher weight fraction of water (j), their solubility may be greatly compromised. To overcome this effect microemulsions containing cyclodexterine have been investigated. Incorporation of cyclodexterines has been shown to improve the solubility of the model steroid drug progesterone in selected microemulsions by 3300 folds.2) Self Microemulsifying Drug Delivery Systems (SMEDDS) can be considered a novel alternative to conventional transdermal delivery systems.3) SMEDDS are preconcentrated (waterfree) microemulsions, made up of oils and surfactants. Upon dilution with an aqueous medium and gentle agitation, these systems can form microemulsions. 4) Enhanced solubility and improved bioavailability are amongst the main advantages of SMEDDS.Before SMEDDS can be used as drug delivery systems it is necessary to characterize the internal structure of the resulting microemulsion. This is highly critical as multiple colloidal and coarse dispersions may coexist. Amongst these are microemulsions, coarse emulsions, various liquid crystalline systems (hexagonal, reverse hexagonal, lamellar, cubic) and gels. These can form upon mixing oils, surfactants and water. Moreover microemulsions are known to have different microstructures namely oil in water (o/w), water in oil (w/o) and bicontinuous. 5) Elucidating the internal structure of microemulsions is of a great interest as the phase behaviour of these systems can influence drug solubility, stability and in vitro release. Phase behaviour of microemulsions can be monitored through visual inspection, measuring electrical conductivity, viscosity, droplets size, density determination, surface tension measurements, and diffusion coefficient measurements. Visual observation is one of the first and foremost techniques used to establish the phase boundaries and distinguish microemulsions from coarse emulsions, liquid crystals and gels. To further differentiate microemulsions form lamellar liquid crystals one can take advantage of other experimental techniques such as polarized light microscopy and viscosity measurements. In general microemulsions display Newtonian flow with low viscosity whilst liquid crystals exhibit non-Newtonian flow and are of relatively high viscosity.5) Furthermore viscosity can also be used to study the microstructure of microemulsions. [6][7][8] Normally o/w microemulsions have a lower viscosity compared to w/o microemulsions in which the more viscous oil ...

Purpose: Bioavailability of transdermal progesterone is low and variable. This may be attributed to transdermal metabolism by the 5α-reductase enzymes or the direct transport to the saliva. The objective of the current study was to evaluate the effect of enzyme inhibition on the bioavailability of transdermal progesterone. Serum and salivary progesterone levels were evaluated to gain a better insight into the mechanism progesterone transport across the skin. Method: Twenty postmenopausal women with a Follicle Stimulating Hormone > 40iu/L were recruited to take part in the study. The subjects were randomly allocated to either dutasteride (n=10) or placebo (n=10). Each group applied either 500mg of non ionic cream or dutasteride cream (2mg/g) to the right arm for 2 weeks. This was followed by applying 500mg of progesterone or progesterone dutasteride cream (equivalent to 40mg of progesterone) for a further 2 weeks. On day 30 blood and saliva were collected for over 12 hours and progesterone concentration was measured. Results: The baseline progesterone concentration on day zero was 0.1 ng/ml. On day 30 baseline progesterone levels increased significantly (p

Abstract. The aim of this work was to investigate the effects of supercritical carbon dioxide (SC-CO 2 ) processing on the release profiles of progesterone (PGN) and Gelucire 44/14 dispersion systems. A fractional factorial design was conducted for optimization of the particles from gas-saturated suspension (PGSS) method and formulation parameters and evaluating the effects of three independent responses: PGSS process yield, in vitro dissolution extent after 20 min (E 20 ) and t 1/2 for prepared PGN dispersion systems. The experimental domain included seven factors measured at two levels to determine which factors represent the greatest amount of variation, hence the most influence on the resulting PGN dispersion systems. Variables tested were temperature (A) and pressure (B) of the supercritical fluid, sample loading (C), SC-CO 2 processing time (D), sonication (E), drug-to-excipient ratio (F) and orifice diameter into the expansion chamber (G). The analysis of variance showed that the factors tested had significant effects on the responses (p value <0.05). It was found that the optimum values of the PGSS process are higher pressure (186 bar), higher temperature (60°C), a longer processing time (30 min) and lower PGN-to-excipient ratio of 1:10. The corresponding processing yield was 94.7%, extent of PGN dissolution after 20 min was 85.6% and the t 1/2 was 17.7 min. The results suggest that Gelucire 44/14-based dispersion systems might represent a promising formulation for delivery of PGN. The preparation of PGN-loaded Gelucire 44/14 dispersion systems from a PGSS method can be optimized by factorial design experimentation.

The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.