Eliphaz Mukasa and Danckwerts PM
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. Now, a cheap rice paper Intraoral Dispersible Film (IDF) has been developed. 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. 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. Sixteen formulations showed variations in their profiles. Formulation 16 proved optimal. The dissolution rate at steady state concentrations of Resveratrol was 29 mg per second and the Permeability coefficient was 389 mg/sec.cm2. Curcumin dissolution rate at steady state concentrations was 0.25 mg 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 dissolved in 47.6 sec. and 71.4 sec. respectively. In this study, after permeation, a concentration of 6.73 mg/ml of Resveratrol and 0.061 mg/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 was 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, given the same dose yielded either undetectable or extremely low (0.006 ± 0.005 μg/ml after 1 hour in blood. Two separate monoglucuronide metabolites yielded a Cmax of ~7.5 μm following a single 5.0 g oral dosage of Resveratrol. The key finding was, 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 intraorally. However, further studies using human subjects need to be performed to prove increased bioavailability in human subjects (Graphical Abstract).
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