Rheological temperature sweeping in a quality by design approach for formulation development and optimization

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Topical drug products, often multi-phase systems, risk phase separation, impacting critical quality attributes (CQAs) like API distribution and homogeneity.
• Ensuring uniform API distribution and physical homogeneity is crucial for pharmaceutical product efficacy and safety.
• Phase separation in topical formulations can lead to inconsistent dosing and reduced therapeutic effectiveness.

Purpose of the Study:

• To implement and refine a rheological temperature sweeping (RTS) method for quantifying CQAs in topical drug products.
• To integrate RTS within a quality by design (QbD) framework for robust pharmaceutical development.
• To identify critical material attributes (CMAs) influencing the stability and homogeneity of emulsions and ointments.

Main Methods:

• Utilized a design of experiments (DoE) approach to prepare various emulsion and ointment compositions.
• Applied rheological temperature sweeping (RTS) to assess product characteristics under varying temperatures.
• Employed principal component analysis (PCA) for multivariate data analysis (MVA) to extract critical responses from RTS data.

Main Results:

• The 'span' after three RTS cycles correlated with emulsion droplet size during stability studies.
• A combination of five principal components (PCs) from RTS effectively differentiated ointment compositions.
• Identified emulsifier concentration (for emulsions) and liquid paraffin content (for ointments) as critical material attributes (CMAs).

Conclusions:

• Rheological temperature sweeping (RTS) provides a quantitative and rapid method for screening liquid and semi-solid pharmaceutical products.
• RTS facilitates pharmaceutical development and formulation optimization by assessing critical quality attributes.
• The study successfully demonstrated the application of RTS within a QbD approach for controlling product CQAs.