Transdermal diffusion stability and clinical efficacy of cosmetic formulations containing Rosa rubiginosa rosehip seed oil

Abstract

This study aimed at investigating cosmeceutical product development from concept to clinical efficacy testing, using Rosa rubiginosa rosehip seed oil, sourced from Southern African soil. Rosehip seed oil contains various bio-actives, such as vitamin C, tocopherols, phytosterols, bio-flavonoids, triglycerides, fatty acids and tretinoin. Unfortunately, tretinoin assays performed during this study, revealed that no detectable amounts of tretinoin were found in the commercially acquired R. rubiginosa seed oil. Research proceeded to assess tretinoin’s stability when dissolved in a 100% rosehip seed oil carrier and in newly formulated final products, containing 20% of the tretinoin spiked rosehip oil. Two investigative cosmetic products (ICPs), namely two oil in water (o/w) emulsions (or emulgels) were formulated during this study and prepared for stability testing purposes. Accelerated stability test procedures were performed, as suggested by the International Conference on Harmonisation (ICH) Guidelines Q1A(R2) and significant physical and/or chemical formulation changes were observed during the long-term (25 ± 2°C/60 ± 5% RH), intermediate (30 ± 2°C/60 ± 5% RH) and accelerated (40 ± 2°C/75 ± 5% RH) storage of the test samples. The stability assessments revealed unacceptably significant changes, higher than 5%, with regards to the following parameters being investigated: the active pharmaceutical ingredient (API) and excipient assays, viscosity and conductivity measurements. Membrane release studies, using hydrophilic polyvinylidene fluoride (PVDF) synthetic membrane filters and employing the Franz cell diffusion method, were performed. As a result, the release of the API from the test formulation was confirmed. The average cumulative concentration of 28.060 μg/cm2, also expressed as an average percentage of 4.97% of tretinoin, was released from the formulations through the membranes after 6 h. The average flux that was obtained by the slope of the straight line between 2 h and 6 h for tretinoin was 9.0586 μg/cm2.h. In vitro skin diffusion studies, utilising the Franz cell diffusion method and excised adomenoplastic human skin, were performed. The concentration of the tretinoin that had permeated the dermatomed skin and reached the receptor compartment was measured as an average concentration of 0.362 μg/ml. An average percentage of 0.071% of tretinoin of the applied dose had hence diffused from the formulations and through the skin after 12 h. It was also revealed that 0.049 μg/ml (0.0095%) of isotretinoin had been retained in the receptor fluid after 12 h. The skin fractionation procedure, utilising the tape stripping method, revealed that the average concentration of tretinoin that had been retained in the stratum corneum-epidermis was 0.020 μg/ml, whereas a slightly higher concentration of 0.027 μg/ml was located within the epidermis-dermis. Finally, in vivo clinical studies were performed on human volunteers, utilising various non-invasive, bio-engineering instruments to evaluate the clinical efficacy. Following the results obtained during the in vivo clinical studies, it was concluded that beneficial clinical efficacy results had been demonstrated during this study. Hence, R. rubiginosa rosehip seed oil could be considered a valuable cosmetic component for the improvement of skin hydration, wrinkle appearance and skin firmness.