Extemporaneously prepared astaxanthin capsules for improved systemic delivery

Abstract

Extemporaneous compounding of supplements or drugs has been practised since the beginning of pharmaceutical disease treatment approaches. In recent years extemporaneous compounding methods have been used for the formulation for a wide variety of drugs and especially for the formulation of natural supplements and remedies. The biggest concern with the practice of extemporaneous compounding is the lack of sufficient regulatory requirements, including safety and quality evaluations, and this lack of regulatory requirements may lead to severe drug/drug or drug/supplement interactions in patients. The use of supplements is increasing in popularity around the world and the use of these supplements, for example astaxanthin, may pose a risk to patients, mainly because the interactions and side effects of these supplements are not well documented. The oral route of administration remains the most popular and convenient route of drug administration, however due to physical- and biochemical barriers, the absorption of these drugs may be compromised. With the safe use of different bioenhancers these absorption problems can be overcome. In previous studies the effectiveness of different bioenhancers, including Aloe vera leaf materials and piperine, have been proven to enhance the intestinal membrane permeability of drugs in ex vivo studies. The purpose of this study was to compound different formulations for use in hard gelatin capsules containing the supplement astaxanthin in combination with different bioenhancers (i.e. Aloe vera gel; Aloe vera whole leaf extract and piperine) to enhance the permeability of astaxanthin across pig intestinal epithelial tissue using an ex vivo transport model. Each formulation was compounded by mixing the different bioenhancers and Pharmacel®, used as a filler, with astaxanthin and filling capsule shells with the different powder mixtures. One formulation contained only astaxanthin and Pharmacel® and was used as the control formulation. The compounded formulations were all evaluated in terms of astaxanthin content and also for dissolution characteristics of astaxanthin in combination with the different piperine concentrations. The permeability of astaxanthin across excised pig intestinal tissue, while combined in the different formulations, was evaluated using the Sweetana-Grass diffusion apparatus. The release of astaxanthin from the formulations containing piperine showed that the inclusion of different concentrations of piperine had mediated an inverse concentration dependent decrease in astaxanthin release with increasing piperine concentrations. Ex vivo transport studies in both apical-to-basolateral and basolateral-to-apical directions, showed that the different bioenhancers, used in the different formulations, did increase the permeability of astaxanthin across the intestinal epithelial tissue when compared to the control formulation, however the different concentrations of the bioenhancers did mediate variable effects on the extent of astaxanthin transport. The highest concentration of Aloe vera gel and -whole leaf extract exhibited similar astaxanthin transport than the control formulation in the apical-to-basolateral direction. However, the low and medium concentrations did mediate an increase in astaxanthin transport in the apical-to-basolateral direction when compared to the control formulation. Furthermore, the extent of astaxanthin transport in the basolateral-to-apical direction was higher than the control formulation in all instances, however the highest concentration mediated a less pronounced increase in astaxanthin transport. The transport of astaxanthin in combination with varying concentrations of piperine resulted in a concentration dependent decrease in the transport of astaxanthin with an increase in piperine concentrations in the apical-to-basolateral direction. This result is in accordance with the dissolution data which showed that astaxanthin dissolution was impeded when the piperine concentration in the formulations was increased. The results of this study showed that the addition of piperine to the capsule formulations mediated the most pronounced transport enhancing effects in combination with astaxanthin followed by Aloe vera whole leaf extract and then aloe vera gel. Although this study showed positive results, additional studies are recommended to further investigate the effects of the selected bioenhancers on astaxanthin membrane permeation.