Buccal mucosal accumulation of dapoxetine using supersaturation, co-solvent and permeation enhancing polymer strategy

Abstract

Purposewe have presented the potential of using mixed solvents, supersaturation and penetration enhancing polymers for achieving a good route for poorly soluble and absorbable drugs like dapoxetine HCl. MethodsThe gel formulation step was based on studying the solubility of DAP. HCl in different organic solvents which can be used as cosolvents. The highest solubility solvent was chosen to be evaluated for its permeation efficiency in pure state and mixed with water in three levels (20, 40 and 60%). The suitable binary mixture was formulated into gel formulations with two levels of drug loading (12 mg/ml and 24 mg/ml) with two levels of polymer concentrations as stabilizing anti-nucleating agents. The stable gel formulations were evaluated for rheological mucoadhesive, drug release and permeation properties. The gels, in general, gave lower flux values than the binary mixture alone. In addition, the permeation profiles were of infinite dose type with a straight steady-state flux line. The chosen formulation was chosen to be compared with the commercial tablets in a bioequivalence in vivo study in human volunteers. ResultsTranscutol P, PEG 200 and PEG 400 were chosen as it achieved the highest DAP. HCl solubility and due to their water miscibility. Transcutol P gave the highest flux among the selected cosolvents due to its permeation enhancing properties. Mixing Transcutol P with water gave exceptional results as the binary mixture of 60% Transcutol in water gave a higher flux than pure Transcutol P. The gel formula gave an AUC0-∞ (1644.5 ± 50.2 ng h/ml) higher than the one form that tablet product (901.26 ± 30.02 ng h/ml). And the relative bioavailability of the buccal gel was 547% As compared to the oral tablet product. Surprisingly, the gel formulation gave a sustained concentration of DAP. HCl over a period of 5 h. ConclusionCombining these findings with the permeation data, it can be suggested that supersaturation and transcutol P helped in the formation of DAP. HCl depot sites inside the buccal mucosa. This could help in the future to formulate dosage forms that can form drug depot sites inside buccal mucosa for sustained drug action.