Design, Development and Characterization of Formulations Selected Carotenoids with Improved Dissolution

Abstract

Carotenoids, being remarkably efficient physical and chemical quenchers of Oxygen and other Reactive Oxygen Species (ROS), have garnered significant attention as potentially protective agents against ROS-mediated disorders. They are thought to be associated with a number of health benefits, which are marked by various epidemiologic studies. Numerous studies have shown an inverse relationship between the presence of various cancers and cardiovascular diseases, and high intake of carotenoids. Two extensively explored carotenoids are Lutein (LUT) and Astaxanthin (AXT). Evidences that carotenoids have many valuable physiological functions in human body persuade the manufactures to insert them into foods and beverages. However, fortification of aqueous-based foods with carotenoids is currently limited due to their poor water-solubility, low bioavailability, and chemical instability. The bioavailability of carotenoids varies widely, from less than 10% from raw uncooked vegetables to more than 50% in oily solutions or in synthetic commercial formulations. Apart from incomplete release of carotenoids from the matrices of foods, one explanation for the low bioavailability is probably dissolution limitations in the gastrointestinal fluids. The clinical significance of the selected carotenoids fostered us to improve their bioavailability. Various techniques have been used to improve dissolution and solubility pattern of selected carotenoids, among which, inclusion complex formation of the active ingredient with suitable non-toxic agents is a promising one. In our project work, we have explored two approaches (1) Cyclodextrin complexation and (2) Solid dispersion in hydrophilic polymers using spray drying for improvement of solubility and dissolution rate. (1) Cyclodextrin complexation: This research work highlights the various studies carried out with cyclodextrins, to improve the solubility of LUT & AXT and characterization of the complexes using spectral analysis viz., FT-IR, DSC, XRD, and NMR. An in vivo SRB assay was performed to demonstrate the uptake of the complex into the cells, thus confirming the increased solubility, and hence bioavailability. (2) Solid dispersion in hydrophilic polymers using spray drying: In this study LUT & AXT microencapsulation with hydrophilic polymers was optimized with improved dissolution rate and antioxidant inhibition activity by using DOE approaches (factorial design and RSM). The optimized formulations were characterised using FT-IR, DSC, XRD and SEM analysis. The approach enables simultaneous evaluation of the effects of different variables such as type of carrier/ wall material, ratio of carrier, concentration of solubilizer and homogenization speed and possible interaction within these factors. This selected QbD approach allowed screening of best compositions and best suited experimental conditions within short period of time and with minimum trials runs. This work is useful tool for exploring the QbD approach for microencapsulation of carotenoids like LUT & AXT.