Enhancing the Solubility of Co-Formulated Hydrophobic Drugs by Incorporating Functionalized Nano-Structured Poly Lactic--glycolic Acid (PLGA) During Co-Precipitation.

: The co-formulation of active pharmaceutical ingredients (APIs) is a growing strategy in biopharmaceutical development, particularly when it comes to improving solubility and bioavailability. This study explores a co-precipitation method to prepare co-formulated crystals of griseofulvin (GF) and dexamethasone (DXM), utilizing nanostructured, functionalized polylactic glycolic acid (PLGA) as a solubility enhancer. : An antisolvent precipitation technique was employed to incorporate PLGA at a 3% concentration into the co-formulated GF and DXM, referred to as DXM-GF-PLGA. The dissolution performance of this formulation was compared to that of the pure drugs and the co-precipitated DXM-GF without PLGA. : Several characterization techniques, including electron microscopy (SEM), RAMAN, FTIR, TGA, and XRD, were used to analyze the PLGA incorporation and the co-precipitated co-formulations. The inclusion of PLGA significantly enhanced the dissolution and initial dissolution rate of both GF and DXM in the DXM-GF-PLGA formulation, achieving a maximum dissolution of 100%, which was not attained by the pure drugs or the DXM-GF formulation. The incorporation of PLGA also reduced the amount of time taken to reach 50% (T) and 80% (T) dissolution. T values decreased from 52 and 82 min (for pure DXM and GF) to 23 min for DXM-GF-PLGA, and the T improved to 50 min for DXM-GF-PLGA, significantly outpacing the pure compounds. Furthermore, incorporating PLGA into the crystal structures greatly accelerated the dissolution rates, with initial rates reaching 650.92 µg/min for DXM-GF-PLGA compared to 540.60 µg/min for DXM-GF, while pure GF and DXM showed lower rates. : This work demonstrates that PLGA incorporation enhances dissolution performance by forming water channels within the API crystal via hydrogen-bonding interactions. This innovative PLGA incorporation method holds promise for developing hydrophobic co-formulations with faster solubility and dissolution rates.