Microarray Plate Method for Estimation of Precipitation Kinetics of Celecoxib under Biorelevant Conditions and Precipitate Characterization.

Authors: Sodhi I, Sangamwar AT
Publication: Mol Pharm
Software: ADMET Predictor®


Study methodologies of supersaturated state are fast developing as pharmaceutical industry is adopting supersaturating drug delivery systems (SDDS) to overcome the solubility issue of drugs. The “parachute” of sobriquet “spring-and-parachute”, which indicates delayed or slowed intraluminal precipitation of drug from SDDS, is of immense importance to formulation scientists since optimal attainment of “parachute” governs the success of SDDS in stabilizing supersaturated state that ensues in enhancement of bioavailability. The studies carried out so far for precipitation assessments have ignored the stochastic nature of nucleation and lack absolute mathematical approach. In the current study, the supersaturated state has been studied in a quantitative manner through microarray plate method with application of the classical nucleation theory (CNT) equation for determination of precipitation kinetics. This microarray plate method is an attempt to pursue the principle of miniaturization in supersaturation assays and involves comprehensive measurements that allows for accounting of the stochastic nature of nucleation. Overcoming the drawbacks of reproducibility and greater material requirement of existing methods, this study aims to quantify the rate of in vivo precipitation through understanding of precipitation profile of model drug, celecoxib, in biorelevant media. Quantification of nucleation rates was made through CNT using tailored criteria and visually represented through temporal precipitation distribution (TPD) plots. Supersaturation stability was also compared through metastable zone width (MSZW). Optical microscopy helped in visualizing the dynamics of precipitation, while solid state characterization assisted in understanding the nature of obtained precipitates. This study identified the short-lived supersaturation of celecoxib and its tendency to precipitate under fasted conditions, which can be correlated with in vivo behavior for formulation design.