Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo

Muhammad Shahid Latif,Md Habibur Rahman,Simona G Bungau,Suliman Y Al Omar,Sheikh Abdur Rashid,Asif Nawaz,Lotfi Aleya,Mohamed M Abdel-Daim,Abul Kalam Azad

doi:10.3390/polym13203455

Abstract

Transdermal drug delivery systems (TDDSs) have become innovative, fascinating drug delivery methods intended for skin application to achieve systemic effects. TDDSs overcome the drawbacks associated with oral and parenteral routes of drug administration. The current investigation aimed to design, evaluate and optimize methotrexate (MTX)-loaded transdermal-type patches having ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) at different concentrations for the local management of psoriasis. In vitro release and ex vivo permeation studies were carried out for the formulated patches. Various formulations (F1–F9) were developed using different concentrations of HPMC and EC. The F1 formulation having a 1:1 polymer concentration ratio served as the control formulation. ATR–FTIR analysis was performed to study drug–polymer interactions, and it was found that the drug and polymers were compatible with each other. The formulated patches were further investigated for their physicochemical parameters, in vitro release and ex vivo diffusion characteristics. Different parameters, such as surface pH, physical appearance, thickness, weight uniformity, percent moisture absorption, percent moisture loss, folding endurance, skin irritation, stability and drug content uniformity, were studied. From the hydrophilic mixture, it was observed that viscosity has a direct influence on drug release. Among all formulated patches, the F5 formulation exhibited 82.71% drug release in a sustained-release fashion and followed an anomalous non-Fickian diffusion. The permeation data of the F5 formulation exhibited about a 36.55% cumulative amount of percent drug permeated. The skin showed high retention for the F5 formulation (15.1%). The stability study indicated that all prepared formulations had very good stability for a period of 180 days. Therefore, it was concluded from the present study that methotrexate-loaded transdermal patches with EC and HPMC as polymers at different concentrations suit TDDSs ideally and improve patient compliance for the local management of psoriasis.

Highlights

Psoriasis is a chronic inflammatory disease affecting about 1–3% of the world’s population [1]
The methotrexate ATR–FTIR spectrum shows its characteristic absorption band as a broad signal at 3450 cm−1 (O–H being stretched from the carboxyl group overlaying with O–H being stretched from crystallized water)
The results of the current study indicate that methotrexate, having ethyl cellulose (EC)/hydroxypropyl methyl cellulose (HPMC) polymers at different concentrations, has the best and excellent patch-forming abilities

Summary

Introduction

Psoriasis is a chronic inflammatory disease affecting about 1–3% of the world’s population [1]. This lifelong disease has an equal gender distribution, and its incidence rate may vary from 50 to 140 new cases per 100,000 cases per year [2]. The management protocols of psoriasis vary depending upon the severity index of the disease [4]. Topical agents constitute first-line therapy, typically sufficient for active management of the disease to combat mild to moderate types of psoriasis [5]. Available systemic tools comprise biological and nonbiological therapies, which are utilized as monotherapy or in combination with other modalities to manage moderate to severe psoriasis [7]

Methods

Results

Conclusion