Formulation Optimization of Diphenhydramine HCl Lotion using Palm Fat–Water Ratios Modeled by Simplex Lattice Design

Palm fat is a natural base derived from a mixture of hydrogenated palm kernel oil and hydrogenated palm kernel stearin, containing triglycerides composed of glycerol and fatty acids. It has potential as an emollient base due to its stability, non-irritant properties, and compatibility with various active substances. However, its application in lotion formulations has not been widely explored. This study aimed to determine the effect of the palm fat-to-water ratio on the physical characteristics and to obtain the optimum formulation using the Simplex Lattice Design (SLD) method for Diphenhydramine Hydrochloride lotion. Three formulations with varying proportions of palm fat and water (20–35% and 57.71–72.71%, respectively) were evaluated through physical characterization (organoleptic, homogeneity, and emulsion type), and response testing (pH, viscosity, spreadability, stability, and drug release flux). The optimum formulation was determined using Design-Expert 13.0.0 based on the desirability value. The results showed that the composition of palm fat and water had a significant impact on the physical characteristics and response variables. The optimum formula consisted of 32.285% palm fat and 53.863% distilled water, with a pH of 4.866; spreadability of 7 cm; viscosity of 34,969 mPas; release flux of 353.374 μg/cm²·min½; and a stability value of 0.753, resulting in a desirability value of 0.929. In conclusion, the composition of palm fat and water strongly influences the physical properties and drug release performance of Diphenhydramine Hydrochloride lotion, and the Simplex Lattice Design effectively determines the optimal formulation.