Synthesis of Microwave Functionalized, Nanostructured Polylactic Co-Glycolic Acid ( nf PLGA) for Incorporation into Hydrophobic Dexamethasone to Enhance Dissolution.

The low solubility and slow dissolution of hydrophobic drugs is a major challenge for the pharmaceutical industry. In this paper, we present the synthesis of surface-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles for incorporation into corticosteroid dexamethasone to improve its in vitro dissolution profile. The PLGA crystals were mixed with a strong acid mixture, and their microwave-assisted reaction led to a high degree of oxidation. The resulting nanostructured, functionalized PLGA ( nf PLGA), was quite water-dispersible compared to the original PLGA, which was non-dispersible. SEM-EDS analysis showed 53% surface oxygen concentration in the nf PLGA compared to the original PLGA, which had only 25%. The nf PLGA was incorporated into dexamethasone (DXM) crystals via antisolvent precipitation. Based on SEM, RAMAN, XRD, TGA and DSC measurements, the nf PLGA-incorporated composites retained their original crystal structures and polymorphs. The solubility of DXM after nf PLGA incorporation (DXM- nf PLGA) increased from 6.21 mg/L to as high as 87.1 mg/L and formed a relatively stable suspension with a zeta potential of -44.3 mV. Octanol-water partitioning also showed a similar trend as the logP reduced from 1.96 for pure DXM to 0.24 for DXM- nf PLGA. In vitro dissolution testing showed 14.0 times higher aqueous dissolution of DXM- nf PLGA compared to pure DXM. The time for 50% (T 50 ) and 80% (T 80 ) of gastro medium dissolution decreased significantly for the nf PLGA composites; T 50 reduced from 57.0 to 18.0 min and T 80 reduced from unachievable to 35.0 min. Overall, the PLGA, which is an FDA-approved, bioabsorbable polymer, can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower required dosage.