The use of grapeseed oil emulsions for the transdermal delivery of selected statins
Van Jaarsveld, Johannes Rudolph
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Statins are used for the medical treatment of hypercholesterolemia, but after oral administration, it may cause gastro-intestinal disturbances and first-pass hepatic metabolism may decrease the bioavailability. Hence, the aforementioned may be avoided through transdermal administration. During this study, four statins (atorvastatin, mevastatin, pravastatin and pitavastatin) were investigated. Not all statins have ideal physicochemical properties for transdermal delivery and therefore, a drug delivery vehicle, i.e. nano-emulsions were utilised and compared to nano-emulgels. Grapeseed oil (penetration enhancer) was utilised as the oil phase during the formulation of the nano-formulas (nano-emulsions and nano-emulgels). High performance liquid chromatography (HPLC) was utilised to analyse the statins and membrane release studies were performed to determine if statins were released from the nano-formulas. Transdermal and topical drug delivery was determined by means of skin diffusion studies and tape stripping, respectively to determine whether the statins were delivered through the skin and into the systemic circulation and/or into the skin. The Franz diffusion cell method was used to conduct membrane release and skin diffusion studies. Cytotoxicity studies were performed on premalignant human immortalised keratinocytes (HaCaT). Two methods were used to indicate possible cell damage, e.g. neutral red (NR) assay and methylthiazol tetrazolium (MTT) assay. Statistical analyses were performed to analyse the variances in the data obtained from the membrane release studies, skin diffusion studies (transdermal and topical) and cytotoxicity studies. Membrane release studies concluded that pravastatin had the highest median flux amongst all the nano-formulas of which the nano-emulgel containing pravastatin had a higher median flux than the nano-emulsion containing pravastatin. Skin diffusion studies revealed that the nano-emulgels improved the transdermal delivery of the statins more than their respective nano-emulsions, and that pitavastatin had the highest median amount per area diffused of all the tested nano-formulas. The nano-emulsions delivered higher median concentrations of the statins in the stratum corneum-epidermis (SCE) than the nano-emulgels. The nano-emulsion containing atorvastatin and the nano-emulgel containing pitavastatin delivered the highest concentration statin from the respective nano-formulas in both the SCE and epidermis-dermis. When the plasma concentrations of the statins after oral administration were compared to the average concentration diffused after transdermal delivery, it was revealed that the nano-formulas had reached higher concentrations for all the statins transdermally than the plasma concentrations, except mevastatin (plasma concentrations are unknown). The half maximal inhibitory concentration (IC50) values from the MTT- and NR-assays indicated that mevastatin (when compared to the other statins) was the most toxic to the HaCaT cells.
- Health Sciences