Enhancement of Topical Delivery of Aceclofenac Using Limonene: A Quality by Design Approach

Abstract

Aceclofenac is a non-steroidal anti-inflammatory drug used to treat pain and inflammation caused by musculoskeletal disorders. Oral administration of Aceclofenac is associated with various gastrointestinal side effects like dyspepsia, abdominal pain, or discomfort. To reduce systemic side effects and to improve patient compliance, a topical gel was formulated using the Quality by Design approach. The Aceclofenac gel was prepared by using Carbopol 974P as a polymer and optimized by custom design. The design suggested 8 runs for 3 factors (Carbopol 974P, limonene and PEG 400) and 2 responses (viscosity, in vitro drug release). The 8 different formulations were prepared and evaluated. The optimized topical gel was characterized for homogeneity, pH, spreadability, viscosity, drug content, in vitro drug release, ex vivo permeation, and stability studies. The optimized Aceclofenac gel formulation predicted global desirability was 0.9980; in-vitro and ex vivo studies were found to be 84.64% and 77.42%. The drug release kinetics were analyzed using zero-order drug kinetics, the highest correlation of 0.999. A stability study was performed, and the shelf life was predicted to be 23.8 months using JMP statistical software. The optimized Aceclofenac gel avoids the first pass metabolism, and it showed a significantly enhanced permeability through the porcine skin and good stability.