<![CDATA[Diclofenac sodium, a widely used NSAID, has limited skin permeability, which reduces its topical efficacy; therefore, a gel-cream formulation combining the rapid absorption of gels with the emollient properties of creams is proposed to enhance drug penetration and patient comfort. To further improve delivery, HAMIN™, a novel natural palm oil–based base with excellent biocompatibility and lipid-enhancing properties, will be combined with HPMC K100M. This thickener stabilises viscosity and prolongs skin contact time, supporting better absorption. This study aimed to develop and optimise a topical gel cream for diclofenac sodium using HAMIN™ and HPMC K100M to achieve ideal physical properties and improved skin penetration. The formulation was statistically optimised using a Simplex Lattice Design (SLD), with HAMIN™ (X₁) and HPMC K100M (X₂) as independent variables, and pH (Y₁), spreadability (Y₂), viscosity (Y₃), extrudability (Y₄), release flux (Y₅), and permeation flux (Y₆) as dependent responses. Optimisation with Design Expert version 13 yielded the ideal composition of 16.84% HAMIN™ and 1.16% HPMC K100M, resulting in predicted values of pH 5.07, spreadability 7 cm, viscosity 4502.25 mPas, extrudability 78.98 N/s, release flux 70.61 µg/cm²√min, and permeation flux 0.4868 µg/cm²/min, with a desirability score of 0.829. Despite a slightly lower release flux, the optimised HAMIN™ and HPMC K100M-based gel cream demonstrated superior skin permeation compared to a commercial emulgel for up to 300 minutes. The incorporation of HAMIN™, a natural palm oil base, offers a novel and effective strategy to enhance the topical delivery of diclofenac sodium via a statistically optimised gel cream formulation.]]>
