Investigating the Influence of Crospovidone’s Manufacturer Variability on Dissolution Profiles of Hydrochlorothiazide Tablets

Abstract

This study examines the influence of crospovidone (CP) manufacturer variability on the dissolution profiles of hydrochlorothiazide (HCTZ) tablets. Four CP batches from different manufacturers were characterized using pharmacopeial and physicochemical tests, including infrared absorption, loss on drying, and scanning electron microscopy (SEM). Significant differences were observed in the particle size distribution, wetting time, and water absorption capacities of the CP batches.

Tablets were formulated using both direct compression and wet granulation methods. For the latter, the superdisintegrant was either added to the binder solution or incorporated intra- or extra-granularly. Disintegration and dissolution tests revealed that both CP concentration and the method of incorporation significantly affected tablet performance. Poly Kovidone and Max-Povidon exhibited superior performance at lower concentrations, while differences between brands became less pronounced at higher concentrations. The extra-granular method notably enhanced drug release profiles.

Statistical analyses, including f₂ similarity factors and MANOVA with Principal Component Analysis (PCA), highlighted significant differences in dissolution behavior among the formulations. These findings emphasize the importance of controlling excipient variability to ensure consistent product performance. The study concludes that a 2% CP concentration is optimal for mitigating source variability and that the extra-granular addition of CP in wet granulation is recommended for enhancing its functional properties.

Materials

Four CP batches were obtained from four different manufacturers: RT. CrossPVP (Rahavard Tamin Pharmaceutical Co, Iran, Batch No # S41C1111115), Max-Povidon A™ (HSH Chemie GmbH, Germany, Lot # CPA7279181), Kollidon® CL (BASF SE, Germany, Lot # 52211852E0), Poly Kovidone® XL (Boai NKY Pharmaceuticals Ltd, China, Batch No # N800282059). Hydrochlorothiazide (CTX Lifesciences, India, Batch No #19HZ11823) was used as the model API. Lactose SD Flowlac® (MEGGLE GmbH & Co. KG, Germany, Lot # L111513821) and dibasic calcium phosphate (Behansar, Iran, Lot # 14–9,801,006) were used as the filler binders, and magnesium stearate (Behansar, Iran, Lot # 13–9,801,005) was used as the lubricant. Polyvinylpyrrolidone k25 (Carl Roth GmbH, Germany, Lot # 265322110) was used as the binder in our tablet formulations.

Yavari, A., Sadjady, S.K., Moniri, E. et al. Investigating the Influence of Crospovidone’s Manufacturer Variability on Dissolution Profiles of Hydrochlorothiazide Tablets. AAPS PharmSciTech 26, 52 (2025). https://doi.org/10.1208/s12249-025-03039-1