Kinetic Monitoring of in vitro Release Testing Using UV-Vis Spectrophotometry with Hydrocortisone Creams.

Abstract

Introduction: A new method for conducting in vitro release testing (IVRT) was developed by adapting Higuchi's square root approximation for use with UV-Vis spectrophotometry, and over the counter hydrocortisone formulations at 0.5% and 1.0% concentrations. This IVRT method was investigated for the required validation elements as specified by abbreviated new drug applications (ANDAs) and USP General Chapter <1724> for linearity and range, precision and reproducibility, and discrimination sensitivity, specificity, and selectivity.

Methods: IVRT kinetic experiments were conducted using UV-Vis spectrophotometer, a quartz cuvette, with measurements collected every 15 s for 5 min, and methanol as the receptor solution. Six measurements of the 1% hydrocortisone formulation were conducted over 3 different days, for a total of 18 measurements. The 0.5% formulation was measured 6 times over 1 day. Release rates were obtained by plotting the slope of Abs242 vs. √t. HPLC was used to demonstrate specificity via an alternate analytical technique and to show membrane inertness.

Results: The hydrocortisone cream formulations demonstrated specificity via HPLC compared to a USP traceable hydrocortisone reference standard. IVRT sensitivity and selectivity were demonstrated by the statistically different release rates (slopes) of the 0.5% vs. the 1% hydrocortisone formulations at 90% confidence interval (75-133.33%). Linearity throughout the duration of the assay was demonstrated through a r2 value of ≥0.97 for each experiment and for each formulation. All intra-run and inter-run precision calculations relating to the IVRT experiments had %CV values of ≤15%.

Conclusion: IVRT experiments were conducted using UV-Vis spectrophotometry kinetic monitoring of 0.5% and 1% hydrocortisone formulations. This IVRT method was validated for specificity, selectivity, sensitivity, linearity and range, precision and reproducibility following the guidance for ANDAs and USP General Chapter <1724>, thus demonstrating the capability of UV-Vis spectrophotometry as a reliable way of discerning release rates of semisolid formulations. This novel approach can be conducted in a matter of minutes as opposed to hours, a vast improvement over conventional IVRT studies.