The current study was aimed to fabricate a transdermal drug delivery system (TDDS) containing Ketoprofen (KTF) and Pregabalin (PGB) for controlled drug release, avoidance of the first-pass metabolism, and increased patient compliance. TDDS of KTF and PGB were formulated using the solvent casting method. Various ratios of hydrophilic polymer (HPMC) and hydrophobic polymers (Eudragit L-100 and Ethyl Cellulose) were employed for the formulation of transdermal patches. PG and oleic acid were used as a permeation enhancer, and PEG-400 was employed as a plasticizer. Surface morphology has confirmed the uniform distribution of drugs throughout the matrix and the excellent compatibility of the selected ingredients. All the formulation showed folding endurance of more than 300, which exhibited that all patches have suitable mechanical strength. One hundred percent flatness also showed good stability of the patches and suitability of the selected ingredients. In vitro drug permeation studies showed more than 97% and 95% release of PGB and KTF, respectively, during the in vitro dissolution studies. The drug release mechanism investigated with various kinetic models exhibited that the rate of drug release was not dependent on initial concentrations of the drug present in the patches and was following the drug diffusion mechanism.
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