Development and characterization of transdermal formulations for treatment of adhd

Abstract

For development of formulations for treatment of ADHD, three approaches were evaluated. First approach developed was microemulsion based gel formulation. Microemulsions are widely used as drug delivery approach for transdermal formulations. For developing microemulsion based formulation, the solubility of drug was determined in different oils, surfactants and co-surfactants and it was observed that Atomoxetine Hydrochloride showed its best solubility in CapmulMCMC8 EP, Cremophore RH 40 and PEG 400 respectively. The best Smix ratio was found to be 3:1. The microemulsion was optimized using mixture optimal design. The optimized formulation was evaluated for various evaluation parameters. The optimized microemulsion was incorporated in the gel base to obtain final dosage form. The drug release study of the final gel was performed ex-vivo using Franz diffusion cell using rat skin as a transdermal barrier. In the second approach, monophasic transdermal system was developed. Here, two main factors affecting diffusion are targeted for enhancement of diffusion which are higher drug concentration gradient and lower path resistance. Higher drug concentration has been achieved by choosing a solvent which is skin compatible and can dissolve highest amount of drug in it. While for lowering path resistance, penetration enhancers are used. Peneteration enhancers changes the property of the skin horny layer so that the resistance becomes less. Capmul MCM C8 was selected as the vehicle because the drug Atomoxetine Hydrochloride has the highest solubility in it. Formulation viscosity was found to be optimum with the use of PVP K90 at 14.44% w/w concentration. Various penetration enhancers were evaluated, out of which ethanol and Trancutol HP showed highest results. Monophasic transdermal formulation was optimised using Simplex Lattice mixture design. The selected factors were concentrations of oil (Capmul MCM C8), Transcutol HP and ethanol. Responses selected were percentage cumulative drug diffused after 4 hours and percentage cu