In silicovalidation and fabrication of matrix diffusion based polymeric transdermal films for repurposing gabapentin hydrochloride in oncogenic neuropathic pain

Abstract

Background: Gabapentin (GBP) is an FDA approved drug for the treatment of partial and secondary generalized seizures, apart from also being used for diabetic neuropathy. GBP displays highly intricate mechanism of action and its inhibitory response in elevated antagonism of NMDA (N-methyl-D-aspartate receptor) receptor and has potential in controlling neuropathic pain of cancer origin . Objective: Therefore, in the present study, we have selected BCATc (Pyridoxal 5’-phosphate dependent branched-chain aminotransferase cytosolic) enzyme that is highly expressed in neuropathic stress conditions and have analysed the GBP as its competitive inhibitor by modeling, docking and checking its pharmacokinetic suitability through ADMET. Though in this study the results exhibited higher efficacy of GBP in controlling neuropathic pain, the drug shows certain potential therapeutic limitations like shorter half-life, repetitive dosing, high inter subjective variability. Methods: Therefore, a suitable and equally efficacious drug delivery method was also designed and developed by loading GBP transdermal patches (GBP-TDP) by solvent evaporation method using PVP and HPMC in ratio of 2:1 as a polymer base for reservoir type of TDP. Also, PEG 400 was used as a plasticizer and PVA (4%) was taken for backing membrane preparation and then the optimized GBP-TDP was subjected for physical characterization, optimization and ex vivo release kinetics. Results and conclusion: The results showed desired specifications with uneven and flaky surface appearance giving avenue for controlled release of the drugs with 75.58% of drug release in 12 hrs., further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain.

Fused 1,4‐Dihydropyridines and Their Corresponding Pyridines: Synthesis, Molecular Modeling and Cholinesterase Inhibition

“…The molecular docking was performed with AutoDock 4.2 software (http://autodock.scripps.edu/). [32] In the first step, the crystallographic reference compound (tacrine-tryptophan hybrid) was re-docked using the AutoDock4.2 package to validate the docking method. To prepare the model of BChE, after removing all ligands and water molecules, all polar hydrogens were added and Kollman charges for all enzyme atoms were computed using AutoDock Tools (ADT, version 1.5.6).…”