Unmasking the Therapeutic Potential of a Bio-enhanced Phloretin Formulation: Formulation, Characterization, and Evaluation

Introduction: Phloretin (PHL, 3-(4-Hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) propan-1- one), is a naturally occurring dihydrochalcone, exclusively found in apple fruit peels, leaves, and Manchurian apricots. It has tremendous benefits as an antioxidant, anti-inflammatory, neuroprotective and anti-cancer agent but its Bioavailability (BA) and penetration across the Blood-Brain Barrier (BBB) is limited as it is a BCS class II drug, thereby hindering its therapeutic applications. Materials and Methods: In this study, we report the formulation, development, and characterization of an Oral Solid Dispersion (ASD) of PHL, designed to enhance its BA and brain distribution, by incorporating non-ionic surfactants like Poloxamer® 188 (P188) and Gelucire® 48/16 (GEL), & excipients like Neusilin® S2 (NEU), in a reproducible, solvent-free approach using melt-fusion technology. Comprehensive characterization included, Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) to compare pure PHL, binary formulations (FPOX: PHL+P188; FGEL: PHL+GEL 48/16), and its Physical Mixtures (PM). In vitro drug release (dissolution, solubility, and accelerated stability) with in vivo Pharmacokinetic (PK) profiling was carried out to assess improved performance. Bioanalytical validation of an RP-HPLC method was done to analyse the samples. Additionally, in vitro antioxidant and anti-inflammatory activities were evaluated. Results and Discussion: The optimized formulation, FPOX with the strategic inclusion of P188 and NEU in an ASD had improved physical stability, dissolution rate, and at an equivalent dose of 10 mg/kg, showed enhanced PK parameters as was analysed by a robust, validated HPLC method. It retained its biological efficacy supporting its potential in phytopharmaceuticals.