Formulation of Polymers-Based Methotrexate Patches and Investigation of the Effect of Various Penetration Enhancers: In Vitro, Ex Vivo and In Vivo Characterization

Abstract

The present study aimed to prepare methotrexate-loaded transdermal patches with different blends of hydrophobic and hydrophilic polymers (Eudragit S-100 and hydroxypropyl methylcellulose) at different concentrations. The polymers employed in transdermal patches formulations served as controlled agent. Transdermal patches were prepared using the solvent casting technique. The suitable physicochemical properties were obtained from the formulation F5 (HPMC and Eudragit S-100 (5:1). Various penetration enhancers were employed in different concentrations to investigate their potential for enhancing the drug permeation profile from optimized formulations. A preformulation study was conducted to investigate drug–excipient compatibilities (ATR-FTIR) and the study showed greater compatibility between drug, polymers and excipients. The prepared patches containing different penetration enhancers at different concentrations were subjected for evaluating different physicochemical parameters and in vitro drug release studies. The obtained data were added to various kinetic models, then formulated patch formulations were investigated for ex vivo permeation studies, in vivo studies and skin drug retention studies. The prepared patches showed elastic, smooth and clear nature with good thickness, drug content, % moisture uptake and weight uniformity. The prepared transdermal patches showed % drug content ranging from 91.43 ± 2.90 to 98.37 ± 0.56, % swelling index from 36.98 ± 0.19 to 75.32 ± 1.21, folding endurance from 61 ± 3.14 to 78 ± 1.54 and tensile strength from 8.54 ± 0.18 to 12.87 ± 0.50. The formulation F5, containing a greater amount of hydrophilic polymers (HPMC), showed increased drug release and permeation and drug retention when compared to other formulated transdermal patch formulations (F1-F9). No significant change was observed during a stability study for a period of 60 days. The rabbit skin samples were subjected to ATR-FTIR studies, which revealed that polymers and penetration enhancers have affected skin proteins (ceramides and keratins). The pharmacokinetic profiling of optimized formulation (F5) as well as formulations with optimized concentrations of penetration enhancers revealed Cmax ranged 167.80 ng/mL to 178.07 ± 2.75 ng/mL, Tmax was 8 h to 10 h, and t1/2 was 15.9 ± 2.11 to 21.49 ± 1.16. From the in vivo studies, it was revealed that the formulation F5-OA-10% exhibited greater skin drug retention as compared to other formulations. These results depicted that prepared methotrexate transdermal patches containing different blends of hydrophobic and hydrophilic polymers along with different penetration enhancers could be safely used for the management of psoriasis. The formulated transdermal patches exhibited sustained release of drug with good permeations and retention profile. Hence, these formulated transdermal patches can effectively be used for the management of psoriasis.

Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery

“…The samples were placed on the sample holder without any processing and scanned between 4000 and 400 cm −1 . Spectra were recorded in triplicates and results were averaged [ 17 ].…”

“…Patches were prepared using polymers either natural or synthetic. The patch is considered as the backbone of topical delivery systems [ 17 ]. Polymers used in the formulation of patches have desirable properties, e.g., hydrophilicity, biocompatibility, swelling ability, and controlled drug release rate [ 18 ].…”

Fabrication of Polymeric Hydrogels Containing Esomeprazole for Oral Delivery: In Vitro and In Vivo Pharmacokinetic Characterization

“…The vortexed plasma was centrifuged for 3 min at 5000 rpm. The estimation of drug plasma content was carried out on HPLC [ 42 ].…”

Estrategia para optimizar la seguridad del paciente en el servicio de dispensación en farmacia comunitaria. Propuesta de listados de verificación

“…También se están investigando nuevos usos, como los parches transdérmicos de insulina para pacientes con diabetes, que permiten mejorar la aceptación (reduciéndose el estrés generado por la propia inyección) y la seguridad en las dosificaciones (secreción de insulina controlada mediante determinación del pH sanguíneo considerando peso y sensibilidad de la insulina suministrada por cada paciente), evitando los errores y los efectos secundarios (24,25) Inconvenientes Es importante comprobar que la pauta posológica del parche sea la adecuada, que el paciente sepa cómo utilizarlo, en qué zonas colocarlo, cómo desecharlo y asegurarse que no se hace un mal uso del parche como doblar, cortar y/o utilizar en repetidas ocasiones el mismo parche (parche de un solo uso). También es conveniente evitar la exposición directa a fuentes de calor, lo cual debe supervisarse durante el seguimiento farmacoterapéutico del paciente (20,25).…”