Enzymatically modified shea butter and palm kernel oil as potential lipid drug delivery matrices

Abstract

Drug formulations based on lipids can enable a significantly better delivery of a pharmaceutically active substance and thus enhance their bioavailability. However, natural fats and oils usually have properties, which do not allow their direct use for drug delivery. Therefore, we have modified palm kernel oil (PKO) and shea butter (SB) via lipase-catalyzed transesterification using either glycerol – to create a diglyceride enriched lipid – or using hexanoic acid via acidolysis – to alter their fatty acid composition – and hence to improve drug solubility of Celecoxib serving as model compound. The most suitable enzyme was immobilized Thermomyces lanuginosus lipase (Novozyme TL IM). The solubility of Celecoxib was determined in SB, pharmaceutical grade SB, glycerol-modified SB, hexanoic acid-modified SB, PKO, glycerol-modified PKO and hexanoic acid-modified PKO. Incorporation of one or two equivalents of hexanoic acid enabled higher Celecoxib solubilization than the diglyceride rich oil. Although structured SB and PKO (15.8 ± 0.4 mg/mL) do not differ significantly (p < 0.05) as per the amount of Celecoxib dissolved, the use of the modified oils enhanced Celecoxib solubility in SB (15.5 ± 1.3 mg/mL) in comparison to Shea butter (7.9 ± 0.5 mg/mL). The lipase-catalyzed modification also improved the miscibility of the oils with surfactants such as Tween 20 and resulted in reduced droplet sizes (<70 nm at oil:surfactant ratios of 1:2 and 1:1) and reduced polydispersity index values of the resulting emulsions.

Practical Applications The structured triglycerides synthesized in this work on the basis of natural shea butter oils could function as suppository bases and oil phase in oral and parenteral lipid-based formulations for improving the solubility and absorption of poorly soluble drugs. As various lipases with distinct selectivity are available for the enzymatic synthesis of structured triglycerides useful for this purpose, further tailor-designed formations should be accessible.

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