Abstract:
Background and Aim Beta-carotene is an important antioxidant for maintaining human health; however, the oral absorption of beta-carotene is low. A new delivery system to solubilise beta-carotene and enhance absorption has developed in this project. Microemulsions (ME) are promising advanced delivery systems with advantages such as transparent appearance, thermodynamically stable with longer shelf-life, ability to solubilise fat soluble compounds and improving oral drug absorption by lymphatic transportation. The aim of the study is to develop and characterise a miroemulsion or SMEDDS delivery systems that can be used for increasing the solubility of beta-carotene with the potential to increase absorption and oral bioavailability. Method A stability indicating HPLC method for beta-carotene was developed. The surfactant composition of the ME was determined by the required HLB method. The optimal ME formulations were found by determining the response surface and pseudo-ternary phase diagram method. The ME were characterized along dilution lines and their phase transition patterns were determined by investigating particle size, conductivity, FTIR spectra, rheological studies and TEM observation. The cytotoxicity of the chosen formulations was evaluated by the SRB dye method on Caco-2 cells. Results and discussions A novel HPLC method was developed to separate beta-carotene and was validated for linearity, resolution, accuracy, intra/interday precision according to the ICH guildlines. Three pseudo-ternary phase diagrams from eight designs had been found with large ME regions greater than 60% of the whole phase diagram area. Four optimized ME formulations with maximum loading capacity of 93.4 μg/ml with droplet size smaller than 200 nm were observed and characterized. Based on the phase transition study results along four dilution lines, characterization studies and SMEDDS region studies in the three chosen designs, the mechanisms of PG and Capmul MCM EP stabilization of the ME interfacial layer have been proposed. The final cytotoxicty studies showed that formulation 57 in design 6 had the highest LD50 and orange oil and Tween 20 were taken as the dominant cytotoxic ingredients among the four chosen formulations. Conclusions The novel o/w ME system, formulation 57 (composition: capmul MCM 15%, Labrasol 15%, PG 35% and water 35%) has been developed, fully characterised and proved with high LD50 and a lower toxicity on Caco-2. Moreover, this ME system exhibited required stability, compatibility, dilutability and a great candidate to be used as a functional drink in the future.