Development and Evaluation of Diclofenac-Loaded Self-Microemulsifying Mouth Dissolving Films (SMMDFs) for Enhanced Oral Delivery

Abstract

Background: Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) with poor aqueous solubility and gastrointestinal (GI) irritation risk. This study introduces a self-microemulsifying mouth dissolving film (SMMDF) combining lipid-based self-microemulsifying drug delivery systems (SMEDDS) with fast-dissolving oral films to improve diclofenac’s dissolution, absorption, and patient compliance.

Methods: Diclofenac-loaded SMMDFs were formulated by solvent casting using hydroxypropyl methylcellulose (HPMC) as film-forming polymer and glycerin as plasticizer, with optimized levels determined via a 3^2 factorial design. Superdisintegrant (crospovidone), an adsorbent (Neusilin® US2), salivary stimulants, and sweeteners were incorporated for rapid disintegration and taste masking. Films were characterized for thickness, tensile strength, elongation, folding endurance, drug content uniformity, surface pH, in vitro disintegration and dissolution, stability (accelerated conditions), and morphology by scanning electron microscopy (SEM). A plain diclofenac film (no SMEDDS) and a commercial tablet were compared as controls.

Results: Optimized SMMDFs disintegrated in ~25 seconds in vitro and released >95% of drug within 5 minutes, whereas a conventional tablet released only ~60% in the same time. Films showed uniform thickness (~25 μm) and weight (~60 mg) with high drug content (~99%) and neutral surface pH (6.8–7.1) eliminating risk of oral irritation. Mechanical properties were optimal for handling: tensile strength and elongation were enhanced by the plasticizer, and films endured >180 folds without breaking. SEM images revealed a rough but uniform microstructure with no crystalline drug, indicating molecularly dispersed diclofenac. The SMMDF was stable over 3 months at 30 °C/75% RH, with no significant change in drug content, disintegration time or dissolution profile.

Conclusions: The diclofenac SMMDF achieved rapid disintegration and dissolution, improved stability, and acceptable mechanical strength. This novel formulation offers fast onset of analgesic action and avoids first-pass metabolism, while providing patient-centric advantages of easy administration, portability, and taste masking. SMMDFs represent a promising platform for enhancing oral delivery of poorly water-soluble drugs like diclofenac