Topical delivery of selected female hormones from different formulations

Abstract

Skin ageing is an unavoidable biological phenomenon inextricably linked to menopause. The rapid and drastic decline in oestrogen levels brought about by menopause has a profound effect on skin integrity and physiology, resulting in atrophic skin changes. Skin becomes wrinkled, thin and dry. Hormone replacement therapy (HRT) has become one of the cornerstones of anti-ageing practices, as it has been shown to improve skin thickness, hydration and elasticity. However, a positive correlation exists between the increased risk of breast cancer in postmenopausal women and conventional HRT. This is cause for concern, as breast cancer is the most common malignancy among women worldwide. Conventional HRT cannot however be used by women at risk due to genetic predisposition or those previously diagnosed with breast cancer. Idexis (compounding pharmacy) aimed to formulate complex systems that deliver female hormones topically, preventing systemic exposure, thereby reducing the risk of hormone-induced breast cancer. The female hormones used in the Idexis products were oestriol, oestradiol and progesterone. For this study, three topical products were provided by Idexis, which included a face serum (FS), eye cream (EC) and male cream (MC). However, due to the classified nature of this study, limited information was made available. During this study, simple oil-in-water (o/w) emulsions were formulated containing the female hormones and selected natural oils (coconut, castor and emu oil), which was used as the oil phase and as penetration enhancer. The aim was to determine which formulation (o/w emulsion versus Idexis product) proved more advantageous for the topical delivery of the hormones, and in addition, to evaluate the efficacy of the polymers used in the Idexis products to inhibit systemic absorption. Initially, three o/w emulsion formulas were characterised and compared; thereafter, the optimised formula was utilised to formulate three o/w emulsions containing the female hormones and the selected natural oils. Oestriol was the only female hormone that was quantifiable during the in vitro diffusion studies. Membrane release studies were performed to determine whether oestriol was released from the respective formulations. The flux values obtained indicated that oestriol was released from all six formulations. Skin diffusion studies were conducted to evaluate the extent of oestriol absorption through the skin, which is indicative of the transdermal delivery. Thereafter, tape stripping was performed to determine the amount of oestriol within the skin layers (topical delivery). Oestriol was delivered transdermally from the Idexis products, and to a lesser extent from the o/w emulsion containing castor oil (CaOE) and the o/w emulsion containing coconut oil (CoOE). It can be concluded that the aim of topical delivery was achieved only by the o/w emulsion containing emu oil (EOE). Lastly, accelerated stability studies were performed on the Idexis products to determine whether any physicochemical changes occurred in the formulations due to elevated temperature and humidity variations, altering the stability and shelf-life of the products. The products were stored at three different conditions (25 °C/60% relative humidity (RH), 30 °C/65% RH and 40 °C/75% RH) for a period of 3 months. No product complied completely with the criteria of the International Conference on Harmonisation (ICH) for stability.