Rheology of Complex Topical Formulations: An Analytical Quality by Design Approach to Method Optimization and Validation

Abstract

Analytical method validation ensures that a method provides trustworthy information about a particular sample when applied in accordance with the predefined protocol. According to regulatory standards, the rheological characteristics of topically applied semisolid formulations are one of the key elements involved in microstructure equivalence documentation. Therefore, for generic drug product manufacturers, it is a dire need to take a step forward in rheology method development and validation procedures. This paper aims to apply Analytical Quality by Design (AQbD) principles towards the development and validation of rheology methods for topical creams, as complex semisolid formulations. Risk assessment was carried out through an Ishikawa diagram and an estimate failure mode, effects, and criticality analysis (FMECA). Sample application, peltier temperature control, and sample rest time were identified as critical method variables (CMVs), and a 23 full factorial design was applied to understand their impact on rotational, creep recovery and, oscillatory measurements. The development of the method was carried out as per the ICH Q8-Q10, and Q14 guidelines and validated according to ICH Q2 (R2) guideline. The method demonstrated adequate precision (RSD < 15%), as well as selectivity. AQbD provided a comprehensive framework for developing a reliable and effective rheology method for this type of formulation.

Effects of Hydrophilic Natural Deep Eutectic Solvents on the Rheological, Textural, and Sensory Properties of Carboxymethylcellulose-Based Cosmetic Hydrogels

“…Rheological characterization was conducted using a Kinexus pro + rheometer (Netzsch, Germany) at a temperature of 25 °C. Conducting rheological studies at 25 °C aligns with real-world usage conditions of the formulation, ensuring that the data reflect practical application . It also assesses product stability, user comfort, and regulatory compliance.…”

“…Conducting rheological studies at 25 °C aligns with real-world usage conditions of the formulation, ensuring that the data reflect practical application. 34 It also assesses product stability, user comfort, and regulatory compliance. All measurements were performed in triplicate with a fresh sample loaded for each run.…”

Hydrogel Formulations for Topical Insulin Application: Preparation, Characterization and In Vitro Permeation across the Strat-M® Membrane

“…A measure of thixotropy is the surface area bounded by curves (an ascending curve-with increasing shear rates and a descending curve-with decreasing shear rates). The small surface areas of the hysteresis loops indicate optimal recovery of the hydrogel structure [28,52]…”

Impact of Time on Parameters for Assessing the Microstructure Equivalence of Topical Products: Diclofenac 1% Emulsion as a Case Study

“…In recent years, the implementation of the components of Quality by Design (QbD) in the manufacture of topical products has been promoted [ 14 , 15 , 16 ]. Hopefully, the consideration of rheological parameters at this stage will imply lower variations between batches [ 17 , 18 ]. Nevertheless, at this moment, the regulatory framework is very demanding, but the rotation of topical products in the market is low; thus, having sufficient batches of the same formulation manufactured at the same time poses a challenge for bioequivalence assessment.…”