Quality-by-Design Compounding of Semisolids Using an Electronic Mortar and Pestle Device for Compounding Pharmacies:...

Area of Science:

• Pharmaceutical Compounding
• Formulation Science
• Quality by Design (QbD)

Background:

• Manual preparation of semisolid formulations exhibits variability in mixing energy and time, potentially compromising Active Pharmaceutical Ingredient (API) distribution.
• Standardized compounding tools are needed to ensure consistent quality and efficacy of pharmaceutical preparations.

Purpose of the Study:

• To evaluate the Electronic Mortar and Pestle (EMP; Unguator™) as a tool for standardized compounding of semisolid formulations.
• To validate stability-indicating UHPLC methods, assess content uniformity, quantify the impact of mixing parameters using Design of Experiments (DOE), and verify cleaning effectiveness.

Main Methods:

• Compounded five representative semisolid formulations (urea, clobetasol, diclofenac, urea + salicylic acid, hydroquinone).
• Validated UHPLC methods per ICH Q2(R2) and stress-tested them; assessed homogeneity via stratified sampling.
• Employed a 3^2 factorial DOE to model the effects of mixing time and speed on API content uniformity and performed cleaning validation using hydroquinone.

Main Results:

• Validated UHPLC methods were stability-indicating and met all ICH criteria.
• Formulations achieved 90-110% label claim with strata coefficients of variation (CV) ≤ 5%.
• DOE identified mixing speed as the dominant factor for most APIs, with optimal parameters identified for reproducible content uniformity; cleaning validation confirmed minimal residues.

Conclusions:

• The Unguator™ offers a practical, parameter-controlled method for standardizing semisolid preparations, achieving reproducible content uniformity.
• DOE-derived relationships define an operational design space, enabling selection of implementable device settings for consistent compounding.
• The study successfully implemented key Quality by Design (QbD) elements, supporting a move towards lifecycle QbD in compounding pharmacies.