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

OBJECTIVE

To enhance the dermal delivery and therapeutic potential of psoralen from Psoralea corylifolia in psoriasis through phytosomal encapsulation.

SIGNIFICANCE: Psoriasis is a chronic inflammatory skin disorder affecting 2-4% of the Western population, characterized by abnormal keratinocyte proliferation and immune system dysregulation. Conventional treatments are limited by their 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 lecithin (SL) vs. egg lecithin (EL) as phospholipid carriers for psoralen dermal delivery.

METHODS

Psoralen-loaded phytosomes were prepared using the thin-film hydration method, with SL or EL. A Box-Behnken Design (a response surface methodology) was used to optimize formulation variables (X1: psoralen extract: soya/egg lecithin w/w, X2: psoralen extract: cholesterol w/w, and 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.

RESULTS

SL-based phytosomes (PPST5) exhibited a small mean particle size (≈ 140.2 ± 2.8 nm) and 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 interactions/complexation. Statistical analysis (ANOVA) showed that lecithin type and phospholipid:drug ratio significantly affected formulation performance (see Table X, ANOVA in Supplementary Table S1).

CONCLUSIONS

SL-based phytosomes improved 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 are required to confirm therapeutic efficacy in psoriasis.