Propranolol as a Model Drug to Treat Smoking Cessation and its Formulation as a Transdermal Patch for Effective Management

Background Smoking causes cancer, heart attacks, and stroke and leads to asthma and breathing problems. Nicotine replacement therapy NRT is considered one of the most widely accepted methods to quit smoking. However, it can lead to relapsed physical and psychological dependence. Aim The present study aimed to explore propranolol, as a model drug to treat relapsed physical and psychological dependence due to NRT in smoking cessation. Furthermore, for its effective management, the transdermal drug delivery system has opted for the effective and long-term release of propranolol. Objective The objective of the present study was to investigate and establish the molecular associations between propranolol with different targets associated with smoking cessation. Materials and Methods The molecular association of propranolol with eight different potential targets, namely, Acetylcholine Binding Protein AChBP, Cannabinoid Receptor, CB1 and CB2, Monoamine oxidase MAO, human dopamine D3 receptor, kainite, Leu- biogenic amine transporters BAT and & alpha;-type peroxisome proliferator-activated receptor, was studied via molecular simulation models. Polymeric films containing propranolol HCI were prepared and evaluated to select a suitable formulation for developing transdermal drug delivery systems TDDS. Films containing different ratios of HPMC K4M, HPMC 15M, and Sodium CMC were prepared by the solvent evaporation technique using PEG 4000 incorporated as a plasticizer, and SLS was used to act as a penetration enhancer. Manufactured transdermal films were physically evaluated for thickness, weight uniformity %, moisture content %, moisture uptake %, drug content % and folding endurance. Results Results indicated that propranolol can interact with all eight receptors at the active binding site. It was found to show considerable interaction with Acetylcholine Binding Protein AChBP, MAO, human dopamine D3 receptor, kainite, and Leu- biogenic amine transporters BAT with the binding energy of -6.27, -6.74, -7.07, -6.84, and -6.63 kcal/mol, respectively. The release rate of propranolol HCI decreased linearly with increasing polymer concentration in the film and depended on the film thickness. In contrast, the quantity of drug release was proportional to the square root of time. Kinetic data based on the release exponent, 'n' in the Peppas model showed that n values were between 0.95 and 1.08, indicating that drug release from polymer matrix was predominantly by diffusion with swelling. Conclusion Transdermal drug delivery of propranolol could act as a potential regulator of all studied targets associated with physical and psychological dependence associated with NRT and smoking cessation. Furthermore, propranolol-loaded transdermal patches with optimized release could be utilized to deliver the drug with optimum bioavailability for a considerable time.