Formulation of a natural intraoral dispersible film (IDF) for intraoral delivery of various natural drugs using edible rice paper film as the carrier vehicle
Date
2016
Authors
Eliphaz, Mukasa
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Abstract
Background and the purpose of study. At present, pharmaceutical researchers are focusing on instantaneous intraoral dispersible technologies as novel drug delivery systems because; they have outstanding advantages over the traditional oral and parenteral routes of drug administration. Some essential natural drugs have low oral bioavailability due to extensive first pass metabolism and pre systemic degradation in the gastrointestinal tract.
Aim. Now, a cheap rice paper Intraoral Dispersible Film (IDF) has been developed
Objectives. In this study, formulation was optimized using the experimental factorial design. The IDFs were loaded with model, natural, anti-cancer drugs, Resveratrol and Curcumin with low oral bioavailability.
Methods. They were evaluated for thickness, folding endurance, swelling behaviour, among others. These related to their drug release properties. Permeation was evaluated using the pig mucosal membrane mounted on a Franz diffusion cell. Taste testing was done to determine acceptability using a taste panel.
Results and Discussions. Sixteen formulations showed variations in their profiles. Formulation 16 proved optimal. The dissolution rate at steady state concentrations of Resveratrol was 29mg per second and the Permeability coefficient was 389 mg/sec.cm2. That of Curcumin was 0.25mg per second and the Permeability coefficient was 42.71 mg/sec.cm2 Resveratrol permeability rate was 0.42 mg/sec. and that of Curcumin was 0.14 mg/sec. Resveratrol Flux was 0.21 mg/sec./cm2. Curcumin Flux was 0.14 mg/sec. / cm2. Drug entrapment was 80% for both molecules. The 20 mg of Resveratrol and Curcumin would then dissolve in 47.6 sec. and 71.4 sec. respectively. In this study, after permeation, a concentration of 6.73mg/ml of Resveratrol and 0.061mg/ml of Curcumin were detected after 2 hours of the experiment on administering only 20 mg of each of the drugs suggesting that Curcumin is 100 times less permeable than Resveratrol. The release profile is a burst release. On contrast, Curcumin oral dose of 2 g/kg to rats yielded 1.35±0.23 μg/ml in 0.83 hours and in humans, the same dose either undetectable or extremely low (0.006±0.005 μg/ml after 1 hour. Two separate mono-glucuronide metabolites yielded Cmax ~7.5 μM following a single 5.0 g oral dosage of Resveratrol.
Conclusion. The key finding is, ex vivo release profiles of the optimized formulation revealed first order release and later zero order. Therefore, it is evident that rice paper IDF could efficiently deliver natural drugs into the systemic circulation. However, later, further studies are needed to prove increased bioavailability to be performed in human subjects
Description
A dissertation submitted to the Faculty of Health Sciences at the University of the Witwatersrand in the fulfillment of the requirements of a Master’s degree in Pharmacy
Johannesburg, 2016
Keywords
Intraoral Dispersible Film