ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Q3 equivalence in semisolids: integrating alkane fingerprinting with rheological analysis for crisaborole ointment

Om Sambhaji Shelke, Jie Feng, Yijie Zhu, Zhong Liu, Yulan Chen, and Zheng Zhang

R&D Centre, Sinomune Pharmaceutical Co., Ltd, Wuxi, China

E-mail: om.shelke@sinomune.com

Received: 26 November 2025  Accepted: 18 February 2026

Abstract:

The development of generic semisolid formulations requires rigorous rheological characterisation to ensure pharmaceutical equivalence with reference-listed products. This study systematically optimised critical rheological parameters, including flow curves, yield stress, linear viscoelasticity, and creep tests, for Crisaborole (CB) Ointment 2%, in alignment with regulatory guidelines. Hydrocarbon profiling by gas chromatography was performed to determine the deformatulation of the ointment base. Method development and validation were performed for flow curves, yield stress, linear viscoelasticity, creep tests, and cone penetration. Rheological, Q3, and drug-release equivalence were assessed for pharmaceutical equivalence, whereas drug-permeation equivalence was demonstrated to support therapeutic equivalence. Euclidean distance coefficient analysis identified Calumet Super White petrolatum (0.956 similarity) as the optimal excipient, closely matching the reference alkane profile. Rheological assessments confirmed shear-thinning behaviour (plastic fluid) with a stable shear rate range (0.2–0.002 s⁻¹) and a yield stress (~ 50 Pa) via an oscillatory stress sweep. Linear viscoelasticity (G′ > G″) and creep compliance (R2 > 0.99) were used to validate structural reliability. Q3 equivalence demonstrated superior purity (undetectable impurities vs. 0.27–0.45% in reference) and comparable viscosity (593,333–629,500 cP), cone penetration (207–223), and globule size (D50: 5.56–6.12 µm). IVRT/IVPT studies confirmed bioequivalence (90% CIs within 75–133.33% and 80–125%, respectively), supported by scaled average bioequivalence analysis. This work establishes a solid framework for developing and assessing the equivalence of rheological methods for generic semisolids.

Keywords: Rheology; Crisaborole; Semisolid; Q3 equivalence; Flow curve; Yield stress; Linear viscoelasticity; Creep test; IVRT; IVPT

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04751-3

Chemical Papers 80 (6) 6083–6104 (2026)