Synthesis of Microwave Functionalized, Nanostructured Polylactic Co-Glycolic Acid (nfPLGA) 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 (nfPLGA), was quite water-dispersible compared to the original PLGA, which was non-dispersible. SEM-EDS analysis showed 53% surface oxygen concentration in the nfPLGA compared to the original PLGA, which had only 25%. The nfPLGA was incorporated into dexamethasone (DXM) crystals via antisolvent precipitation. Based on SEM, RAMAN, XRD, TGA and DSC measurements, the nfPLGA-incorporated composites retained their original crystal structures and polymorphs. The solubility of DXM after nfPLGA incorporation (DXM-nfPLGA) 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-nfPLGA. In vitro dissolution testing showed 14.0 times higher aqueous dissolution of DXM-nfPLGA compared to pure DXM. The time for 50% (T50) and 80% (T80) of gastro medium dissolution decreased significantly for the nfPLGA composites; T50 reduced from 57.0 to 18.0 min and T80 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.

Development of nano structured graphene oxide incorporated dexamethasone with enhanced dissolution

We present the development of nanographene oxide (nGO) incorporated dexamethasone (DXM) composites (DXM-nGO) with enhanced aqueous solubility. Antisolvent precipitation was used for successful incorporation of nGO into DXM, a popular COVID-19 drug. The study focuses on morphology and dissolution performance of the formulated DXM-nGO, which were characterized using scanning electron microscopy (SEM), Raman spectroscopy, X-ray diffraction (XRD), Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA). In vitro dissolution profile showed that for a DXM-nGO containing 0.5% nGO showed that time for 50% dissolution (T50) dropped from 39 min to 24 min, while time for 80% dissolution (T80) went from not dissolved state to 56 min for the same composite. In general, the nGO incorporation into DXM showed enhanced solubility, and in vitro dissolution data suggest that the nGO may be a candidate for successful bioavailability improvement.