Abstract

Natural products remain a vital source of bioactive compounds; however, their incorporation into pharmaceutical formulations presents considerable technological hurdles. This study focused on the design and optimization of a topical self-emulsifying drug delivery system that integrates an ethanolic phytotherapeutic extract of Mammea americana L. Employing a quality by design (QbD) approach, the quality target product profile was established, and a comprehensive risk assessment was performed. Excipients were selected based on solubility screening and emulsification efficiency. Characterization of phytochemical markers, including tannins, polyphenols, and coumarins, was achieved using Fourier Transform Infrared Spectroscopy and High-Performance Liquid Chromatography–Mass Spectrometry, supporting a characterization of the extract. The optimized formulation, comprising rosemary oil and polysorbates 20/80, was duplicated and subjected to extensive physicochemical analysis. Dynamic light scattering revealed multimodal droplet size distributions with nanometric fractions (~21–26 nm) alongside submicrometric and micrometric populations. Zeta potential measurements around −18 mV suggested moderate electrostatic stability, further supported by steric stabilization from non-ionic surfactants. The findings validated the predictive capability of the Box–Behnken design model, while also underscoring challenges related to the complexity of natural extracts. In summary, the QbD strategy successfully overcame formulation obstacles, facilitating the development of a reproducible and innovative topical delivery system based on plant-derived compounds with significant therapeutic promise.

Key words: Self-Emulsifying Drug Delivery Systems, Quality by Design, Topical Administration, Plant Extracts, Box-Behnken Design