Development of vitamin C and E fixed-dose combination, multiple-unit, solid oral delivery systems

Abstract

Oral drug delivery is one of the most preferred and user-friendly routes of drug administration, however, vitamin C and vitamin E have poor and unreliable bioavailability at doses intended for anti-oxidant effects. This may be due to the instability (vitamin C), poor solubility (vitamin E) or the poor permeability in the intestinal tract. Functional excipients such as Aloe vera gel (AVG) and sodium lauryl sulphate (SLS) may be incorporated into drug delivery systems to overcome the poor bioavailability. AVG and SLS act as absorption enhancers and have been proven to increase membrane permeability and bioavailability of both vitamins C and E. The general aim of this study was to formulate multiple unit pellet systems (MUPS) with AVG and SLS to enhance the bioavailability and permeability of vitamins C and E. MUPS are considered to be an interesting alternative to conventional tablets and capsules. MUPS provide several advantages over single-unit dosage forms, which include a relatively high degree of homogeneous dispersion of the sub-units (e.g. pellets) in the gastro-intestinal tract, less local irritation effects, less variation in transit time, and lower fluctuations in peak plasma levels. Beads containing both vitamin C and E with AVG and SLS as functional excipients were produced by means of extrusion spheronisation. The beads were characterised in terms of uniformity of mass, friability, assay and bead size distribution. Drug release studies were performed by means of dissolution tests. Ex vivo transport studies were done using a Sweetana-Grass diffusion apparatus to determine the transport of vitamin C and E for a 2 hour period. The samples obtained were analysed by means of high-performance liquid chromatography (HPLC) using validated methods. Ex vivo transport studies showed that the tested absorption enhancers (AVG and SLS) formulated into MUPS capsule formulations succeeded in enhancing the permeability of vitamin C across excised pig intestinal tissue. No transport of vitamin E across the excised intestinal tissues was observed for the vitamin E MUPS capsule formulations and retention of vitamin E in the tissues was therefore assessed. These retention studies showed that AVG and SLS improved the ability of vitamin E to be delivered into the epithelial tissues. Promising results were obtained, but in vivo studies are needed to prove that the bioavailability enhancement effects can lead to clinically significant blood plasma levels.