QbD assisted formulation, optimization and characterization of psoralen phytosome prepared through thin film hydration method

ObjectiveTo enhance dermal delivery and therapeutic potential of psoralen from Psoralea corylifolia in psoriasis through phytosomal encapsulation.SignificancePsoriasis is a chronic inflammatory skin disorder affecting 2-4% of the Western population, characterized by abnormal keratinocyte proliferation and immune dysregulation. Conventional treatments are limited by side effects and poor adherence. Psoralen shows anti-psoriatic activity but its therapeutic use is limited by poor dermal penetration and low bioavailability; enhancing its solubility and skin permeation could potentially improve its local effectiveness. To our knowledge, this is the first report of psoralen encapsulation into phytosomes, and the first comparative evaluation of soya vs. egg lecithin as phospholipid carriers for psoralen dermal delivery.MethodsPsoralen-loaded phytosomes were prepared using the thin-film hydration method with soya lecithin (SL) or egg lecithin (EL). A Box-Behnken Design (a response surface methodology) optimized formulation variables (X1: psoralen extract: soya/egg lecithin w/w, X2: psoralen extract: cholesterol w/w, X3: Reaction temperature °C) and responses (Y1: entrapment efficiency % and Y2: particle size nm). Optimized formulations were characterized for particle size, PDI, entrapment efficiency (EE%), loading capacity, zeta potential, drug content, FTIR, DSC, and in-vitro release.ResultsSL-based phytosomes (PPST5) exhibited small mean particle size (≈ 140.2 ± 2.8 nm), higher entrapment efficiency (≈ 90.89 ± 0.82%), compared to EL-based phytosomes (PPET2). Both formulations demonstrated acceptable colloidal stability (zeta potential > |22 mV|) and high drug content. In vitro release studies showed that SL-based phytosomes provided sustained and significantly higher psoralen release (98.98 ± 1.31%) in 24h compared to the psoralen suspension (63.15 ± 13.48%) and EL-based phytosomes (88.54 ± 2.04%). FTIR and DSC data are consistent with psoralen-phospholipid interaction/complexation. Statistical analysis (ANOVA) showed that lecithin type and phospholipid:drug ratio significantly affected formulation performance (see Table X, ANOVA in Supplementary Table S1).ConclusionsSL-based phytosomes improve psoralen dermal delivery by enhancing entrapment, penetration, and providing sustained release. These findings support phytosomal encapsulation as a promising topical delivery strategy for psoralen; however, direct bioavailability and in vivo/ex vivo validation is required to confirm therapeutic efficacy in psoriasis.