- 學位論文
Development of sublingual dripping pill delivery system for improving the oral bioavailability of Curcumin, Quercetin and Resveratrol in Rabbits
Development of sublingual dripping pill delivery system for improving the oral bioavailability of Curcumin, Quercetin and Resveratrol in Rabbits
摘要
Quercetin, Resveratrol and Curcumin have attracted the most attention from researcher due to their apparent therapeutic activity in numerous disease states such as cardiovascular disease, cancer, asthma, diabetes, neurodegeneration, aging and stress. Unfortunately, the therapeutic potential of these compounds is limited by their poor oral bioavailability. Major reasons postulated are due to their low water solubility, poor intestinal permeability, rapid, extensive metabolism in the intestine and liver. Our research aims to improve bioavailability of Quercetin, Resveratrol and Curcumin by developing Quercetin/ Resveratrol/ Curcumin dripping pill for sublingual administration. The polyethylene glycol 6000-based dripping pills were prepared by the hot melt method with rapid cooling. The effect of various surfactants (Capryol 90, Labrasol, Lecithin, Cremophor ELP and Phosphatidylglycerol (PG)) on dripping pill dissolution was investigated. Ac-Di-Sol (Croscarmellose sodium), a superdisintegrant, and/or effervescent agent was utilized as disintegration agent. The optimal formulation consisted of API, PEG 6000, PEG 400, Ac-Di-Sol, Lecithin (excluding Resveratrol dripping pill formulation), Mannitol and Citric acid. The dissolution results showed an initial burst release with 97.41 ±2.59% Curcumin, 83.89 ±5.99% Quercetin, 79.5 ± 18.3 % Resveratrol released from these dripping pills after 15mins in medium of 1% Tween simulated salivary fluids. The in vivo experiment was carried out to confirm the usefulness of the final formulation compared to control group of solution. The pharmacokinetic results manifested insignificant difference in relative bioavailability (BA) between Quercetin/Resveratrol dripping pills and respective solution. However, Curcumin dripping pills showed the improved relative BA of 2.6 times compared to Curcumin solution prepared in PEG 400. In this study, Quercetin/ Resveratrol/ Curcumin dripping pills for sublingual administration were successfully prepared. The results about Curcumin dripping pill demonstrated that the dripping pill delivery system is an approach to the enhancement of BA of a poorly soluble component. Keywords: Quercetin, Resveratrol, Curcumin, dripping pill, sublingual, solid dispersion.
並列摘要
Quercetin, Resveratrol and Curcumin have attracted the most attention from researcher due to their apparent therapeutic activity in numerous disease states such as cardiovascular disease, cancer, asthma, diabetes, neurodegeneration, aging and stress. Unfortunately, the therapeutic potential of these compounds is limited by their poor oral bioavailability. Major reasons postulated are due to their low water solubility, poor intestinal permeability, rapid, extensive metabolism in the intestine and liver. Our research aims to improve bioavailability of Quercetin, Resveratrol and Curcumin by developing Quercetin/ Resveratrol/ Curcumin dripping pill for sublingual administration. The polyethylene glycol 6000-based dripping pills were prepared by the hot melt method with rapid cooling. The effect of various surfactants (Capryol 90, Labrasol, Lecithin, Cremophor ELP and Phosphatidylglycerol (PG)) on dripping pill dissolution was investigated. Ac-Di-Sol (Croscarmellose sodium), a superdisintegrant, and/or effervescent agent was utilized as disintegration agent. The optimal formulation consisted of API, PEG 6000, PEG 400, Ac-Di-Sol, Lecithin (excluding Resveratrol dripping pill formulation), Mannitol and Citric acid. The dissolution results showed an initial burst release with 97.41 ±2.59% Curcumin, 83.89 ±5.99% Quercetin, 79.5 ± 18.3 % Resveratrol released from these dripping pills after 15mins in medium of 1% Tween simulated salivary fluids. The in vivo experiment was carried out to confirm the usefulness of the final formulation compared to control group of solution. The pharmacokinetic results manifested insignificant difference in relative bioavailability (BA) between Quercetin/Resveratrol dripping pills and respective solution. However, Curcumin dripping pills showed the improved relative BA of 2.6 times compared to Curcumin solution prepared in PEG 400. In this study, Quercetin/ Resveratrol/ Curcumin dripping pills for sublingual administration were successfully prepared. The results about Curcumin dripping pill demonstrated that the dripping pill delivery system is an approach to the enhancement of BA of a poorly soluble component. Keywords: Quercetin, Resveratrol, Curcumin, dripping pill, sublingual, solid dispersion.