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In silico validation and fabrication of matrix diffusion based polymeric transdermal patches for repurposing gabapentin hydrochloride in neuropathic pain.

BACKGROUND
Gabapentin (GBP) is an FDA approved drug for the treatment of partial and secondary generalized seizures, apart from being used for diabetic neuropathic pain. GBP displays highly intricate mechanism of action and its inhibitory response in elevated antagonism of NMDA (N-methyl-D-aspartate receptor) receptor and thus, can be repurposed for controlling neuropathic pain.


OBJECTIVE
Therefore, in the present study, we have selected hBCATc (human Pyridoxal 5'-phosphate dependent branched-chain aminotransferase cytosolic) gene that is highly expressed in neuropathic stressed conditions. Thereafter, have analyzed the GBP as its competitive inhibitor by homology modeling, molecular docking, also predicting its structural alerts and pharmacokinetic suitability through ADMET. However, GBP was found to be a potential drug in controlling neuropathic pain, still it has certain critical pharmacokinetics limitations therefore, the need for its targeted delivery was required and the same was attained by designing a GBP loaded trandermal patch (TDP).


METHODS
A suitable and equally efficacious GBP - TDP was developed 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 an avenue for controlled release of the drugs with 92.34 ± 1.43% of drug release in 10 h, further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain.