Explicating the molecular level drug-polymer interactions at the interface of supersaturated solution of the model drug: Albendazole.

Supersaturation as a formulation principle relates to the aqueous solubility of poorly soluble drugs in solution . However, supersaturation state of drugs tends to crystallize because of its thermodynamic instability thereby compromising the solubility and biopharmaceutical performance of drugs. The present study aims to investigate the supersaturation potential of albendazole (ABZ) and its precipitation via nucleation and crystal growth. We hypothesized the use of polymers will avoid ABZ precipitation by interacting with drug molecules. The drug polymer interactions are characterized using conventional methods of Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR) and Polarized light microscopy (PLM). We have used a novel approach of sum frequency generation (SFG) vibrational spectroscopic in exploring the drug polymer interactions at air-water interface. Recently we have reported the SFG for e rifaximin-polymer interactions (Singh et al., 2021). The supersaturation assay, saturation solubility studies and nucleation induction time analysis revealed polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP K30) as effective precipitation inhibitors thereby enhancing the ABZ equilibrium solubility and in vitro supersaturation maintenance of ABZ. Further, modification in the solid state of ABZ has confirmed the influence of polymers on its precipitation behaviour. We conclude that PVA and PVP K30 act as nucleation and crystal growth inhibitor, respectively for the precipitation inhibition of ABZ.

Insights on role of polymers in precipitation of celecoxib from supersaturated solutions as assessed by focused beam reflectance measurement (FBRM).

Supersaturating drug delivery systems (SDDS) have dominated the commercial and academic spheres owing to their potential in overcoming the solubility issue of poorly soluble drugs. Precipitation inhibitors are used as excipients in such formulations which has necessitated the development of supersaturation assays that evaluate their precipitation-inhibition efficacy. Such assays are able to give relative estimates of polymer efficacy ceteris paribus within a given set-up. However, the estimates of different laboratories cannot be compared with each other owing to high variability in procedure. Microarray plate method allows comprehensive replicates and decent statistics that make the method an edge over the other exploratory assays. In the current study, the precipitation-inhibition performance of three polymers on the precipitation of a model BCS class II drug was evaluated using the microarray plate method. Quantitative estimations were made through application of Poisson equation for nucleation rates and area under curve. Insights of the precipitation process at particle level were obtained through focused beam reflectance measurement (FBRM) technique coupled with end-process PVM imaging. Through real-time particle size analysis, FBRM technique demonstrated the potential for discerning the role of polymer as nucleation-inhibitor or crystal growth inhibitor. The events observed in the scaled-up FBRM analysis could be correlated with the events observed visually and spectrophotometrically. Powder X-ray diffraction and scanning electron microscopy were performed to capture the influence of polymers on the precipitates formed. This study was able to demonstrate the applicability of microarray plate method for quantitative estimations of precipitation kinetics that can be utilized for excipient screening for poorly soluble drugs having intra-luminal precipitation as a problem. FBRM analysis is highly valuable to gain mechanistic insights and put to rest the prevalent conjecture-based role attribution for polymers.