In-Silico Validation and Fabrication of Matrix Diffusion-Based Polymeric Transdermal Patches for Repurposing Gabapentin Hydrochloride in Neuropathic Pain

Title:In-Silico Validation and Fabrication of Matrix Diffusion-Based Polymeric Transdermal Patches for Repurposing Gabapentin Hydrochloride in Neuropathic Pain

Volume: 20 Issue: 6

Author(s): Manisha Singh*, Shriya Agarwal, Pranav Pancham, Vinayak Agarwal, Harleen Kaur and Ramneek Kaur

Affiliation:

• Department of Biotechnology, Centre for Emerging Diseases (CFED), Jaypee Institute of Information Technology (JIIT), Noida, U.P.,India

Keywords: Pharmacokinetics, homology, modelling, molecular docking, controlled drug release, physicochemical characterization.

Abstract:

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 a 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 (humanPyridoxal 5’-phosphate- dependent branched-chain aminotransferase cytosolic) gene that is highly expressed in silico validation through neuropathic stressed conditions. Thereafter, have analysed the GBP as its competitive inhibitor by in silico validation through homology modelling, molecular docking, also predicting its structural alerts and pharmacokinetic suitability through ADMET. However, and GBP was found to be a potential drug in controlling neuropathic pain, still, it has certain critical and pharmacokinetic limitations; therefore, the need for its targeted delivery was required, and the same was attained by designing a GBP loaded transdermal patch (GBP-TDP).

Methods: A suitable and equally efficacious GBP - TDP was developed by a solvent evaporation method using PVP and HPMC in the 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: 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 hours, further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain.

Conclusion: In this study, we have repurposed Gabapentin to treat diabetic neuropathy and validated the same by conducting a detailed in silico evaluation starting from homology Modelling of the target protein hBCATc, cross verified by the Ramachandran plot analysis with the most favoured region of 92.1% (encompassing 303 residues out of 386).

Cite this article as:

Singh Manisha *, Agarwal Shriya , Pancham Pranav , Agarwal Vinayak , Kaur Harleen and Kaur Ramneek , In-Silico Validation and Fabrication of Matrix Diffusion-Based Polymeric Transdermal Patches for Repurposing Gabapentin Hydrochloride in Neuropathic Pain, CNS & Neurological Disorders - Drug Targets 2021; 20 (6) . https://dx.doi.org/10.2174/1871527320666210212111158