The transdermal route as an alternative for the delivery of drugs for epilepsy and psychotic disorders
Creators: name: Virani, Amitkumar M.
Publisher: name: No Publisher Supplied
Year: 2023

description: Transdermal drug delivery has gained recognition as a promising non-invasive method of administering drugs with several advantages over the traditional oral drug delivery, including extended therapeutic effects, reduced side effects, avoidance of the hepatic first-pass metabolism and target drug delivery. However, the skin presents a significant barrier to drug absorption, and not many drugs can passively diffuse through the skin in amounts sufficient to produce a therapeutic effect. Different methods are being explored to get through this skin barrier, including use of chemical penetration enhancers and microemulsion drug delivery system to increase the drug transport across the skin. The objective of this research work is to explore the feasibility of developing transdermal drug delivery systems for drugs used in the treatment of psychotic disorder and epilepsy. The microemulsion system provides opportunity to use different chemical penetration enhancer in combination to get synergistic effect which increases the drug transport across the skin. Firstly, we have evaluated feasibility of transdermal delivery of olanzapine (OLZ) as satisfactory alternative drug delivery system for the oral route using various chemical penetration enhancers (CPEs). The aim of this study was to obtain the information about the impact and effects of various CPEs on the drug’s permeability. The effects of different CPEs have been determined on permeation profile of OLZ from formulation through human cadaver skin. A control formulation of OLZ in propylene glycol (PG) was prepared for a comparison study against the formulations containing chemical penetration enhancers. Different five chemical penetration enhancers (Oleic Acid, Cineole, Isopropyl Alcohol, Tween 80 and N-methyl pyrrolidone) in concentration of 5% were individually added to the formulation containing OLZ in PG. The in-vitro permeation study was carried out using Franz diffusion cell. Samples from the recipient chamber were collected at 2h, 4h, 8h, 12h and 24h at room temperature over a period of total 24 h. Based on the results obtained, different CPEs have a significant impact on OLZ permeability compared to that of a control formulation. The OLZ formulation with 5% Oleic Acid (OA) showed highest permeability through human cadaver skin. The cytotoxicity study results support the fact that studied models were non-toxic. Secondly, we have investigated the effect of various penetration enhancers on the transdermal delivery of oxcarbazepine an anti-epileptic drug. The ex-vivo permeation experiments were conducted by using vertical Franz diffusion cells mounted with human cadaver skin to study the percutaneous absorption of oxcarbazepine. Various penetration enhancers (represent enhancer groups - terpenes, ether alcohol, fatty acid, pyrrolidone) at concentration from 5% to 20% w/w were selected. Formulation containing oxcarbazepine an anti-epileptic drug, propylene glycol as a solvent and penetration enhancer were used for evaluating drug penetration. Oxcarbazepine was shown to permeate through human skin in vitro following the use of different penetration enhancers. The microemulsion system was prepared using the chemical enhancers. The selection of microemulsion components were based on its solubilization capacity and enhanced permeation activity. Microemulsions were prepared using selected penetration enhancers, enhanced oxcarbazepine permeation. Furthermore, microemugel was prepared using thickening agent shows comparable permeation as microemulsion. Lastly, we have investigated the effect of various penetration enhancers on the transdermal delivery of risperidone for psychotic disorder. The chemical enhancers modify skin lipids in different ways and the mechanism of action is linked to their ability to interact with skin lipids, that increase the drug passage through skin and thus contribute to increased permeability. Microemulsions were prepared using selected penetration enhancers with dual role as penetration enhancer as well as component of microemulsion. Our study showed that the flux and the amount permeated of risperidone were significantly increased with the incorporation of various penetration enhancers in the microemulsion formulation. Microemulsion prepared from oleic acid (15%) as oil, tween 80 (15%) as surfactant and isopropyl alcohol (20%) as co-surfactant shows highest permeation across the human cadaver skin. This novel in vitro research disclosed that an optimized microemulsion formulated using penetration enhancers was able to increase permeation of risperidone by 14-fold compared to the control formulation. Further, the stability study of the final microemulsion shows that the microemulsion was stable at room temperature (25°C) and at accelerated temperature (40°C) conditions with no change in the drug content, visual appearance and globule size conclude stable product. In conclusion, the study demonstrates that utilizing chemical penetration enhancers and optimized microemulsion formulations are feasible approaches for developing transdermal drug delivery systems for psychotic and epilepsy treatments. These findings contribute to the advancement of alternative drug delivery methods that can potentially enhance treatment outcomes for these diseases.