Abstract
abstract This work aimed to investigate in vitro the influence of monoolein (MO) on progesterone (PG) transdermal delivery and skin retention. Information about the role of MO as an absorption enhancer for lipophilic molecules can help on innovative product development capable of delivering the hormone through the skin in a consistent manner, improving transdermal therapy of hormonal replacement. MO was dispersed in propylene glycol under heat at concentrations of 0% (control), 5% w/w, 10% w/w and 20% w/w. Then, 0.6% of PG (w/w) was added to each formulation. Permeation profile of the hormone was determined in vitro for 48 h using porcine skin in Franz diffusion cells. PG permeation doubled when 5% (w/w) of MO was present in formulation in comparison to both the control and higher MO concentrations (10% and 20% w/w). An equal trend was observed for PG retention in stratum corneum (SC) and reminiscent skin (E+D). PG release rates from the MO formulations, investigated using cellulose membranes, revealed that concentrations of MO higher than 5% (w/w) hindered PG release, which indeed negatively reflected on the hormone permeation through the skin. In conclusion, this work demonstrated the feasibility of MO addition (at 5% w/w) in formulations as a simple method to increase transdermal PG delivery for therapies of hormonal replacement. In contrast, higher MO concentrations (from 10% to 20% w/w) can control active release, and this approach could be extrapolated to other lipophilic, low-molecular-weight molecules.
Highlights
The use of oral progesterone (PG, Figure 1) is approved by the FDA and by other international regulatory agencies and is the most conventional strategy for hormone replacement therapy in menopausal women (Studd, 2014).It is undeniable, that transdermal delivery of PG would be more advantageous than oral therapy, if considered the possibility to obtain a controlled and prolonged hormone delivery to the blood and the avoidance of first-pass metabolism in the liver, which guarantee a more consistent bioavailability of the hormonal substance (Silva et al, 2010)
This study aimed to investigate the feasibility of MO to be used as permeation enhancer in formulations incorporating PG for enhancing its transdermal delivery
MO was dispersed in propylene glycol in three different concentrations and PG permeation from these formulations were evaluated relatively to a control
Summary
The use of oral progesterone (PG, Figure 1) is approved by the FDA and by other international regulatory agencies and is the most conventional strategy for hormone replacement therapy in menopausal women (Studd, 2014).It is undeniable, that transdermal delivery of PG would be more advantageous than oral therapy, if considered the possibility to obtain a controlled and prolonged hormone delivery to the blood and the avoidance of first-pass metabolism in the liver, which guarantee a more consistent bioavailability of the hormonal substance (Silva et al, 2010). The use of oral progesterone (PG, Figure 1) is approved by the FDA and by other international regulatory agencies and is the most conventional strategy for hormone replacement therapy in menopausal women (Studd, 2014). PG potential in preventing estrogen-stimulated cell proliferation has not yet been fully explored because current formulations and devices are unable to deliver therapeutically relevant progesterone concentrations (Zava et al, 2014) In this context, some research groups have devoted their efforts in using many different strategies to overcome the stratum corneum (SC) barrier of skin. A more recent study determined the efficacy of a transdermal nanostructured formulation of PG combined with estriol, and preliminary clinical studies demonstrated the system was safe and effective (Botelho et al, 2014)
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