Solubility enhancement of BCS class II drugs via in-situ loading onto MIL-101(Cr) in a green solvent system

Abstract

This study explores strategies to enhance the solubility of Biopharmaceutics Classification System (BCS) Class II drugs: felodipine (FDP), ibuprofen (IBU), and ketoprofen (KP), by incorporating them into MIL-101(Cr) metal–organic frameworks (MOFs). Two loading methods are investigated: conventional solvent impregnation and a novel in-situ synthesis method. The in-situ strategy incorporates drug molecules during MOF crystallisation while replacing toxic hydrofluoric acid with acetic acid and aqueous solvents, thereby aligning with green chemistry principles. Comprehensive characterization (FESEM, BET, FTIR, XRD, zeta potential) confirmed successful drug loading but revealed reduced crystallinity and altered morphology post API encapsulation. MIL-101(Cr) exhibited exceptional adsorption capacities (Langmuir values of 904.7 mg/g for IBU, 954.4 mg/g for KP and 416.4 mg/g for FDP), surpassing literature benchmarks. The drug release studies in phosphate-buffered saline (PBS) revealed solubility enhancements ranging from 4.1 to 7.3 g/L, enabling the reclassification of all drugs from “poorly soluble” to “soluble”. Density functional theory (DFT) calculations elucidated π–π stacking and hydrogen bonding as key drug–MOF interactions. This work establishes MIL-101(Cr) as a high-performance and environmentally sustainable carrier for enhancing the oral bioavailability of BCS Class II therapeutics.<br/