Development of pellets for oral lysozyme delivery by using a quality by design approach

• QbD is essential to appropriately formulate an enzyme into solid dosage form.
• Linear estimation of enzyme activity is not appropriate for determination of design space.
• Complex relationships exists between enzyme activity and local overwetting.

The concept of Quality by design is of increasing importance in the pharmaceutical industry, especially in the development of biotechnologically produced active pharmaceutical ingredients (APIs). These proteins/peptide-like materials are usually more sensitive than small molecules to the environmental and process parameters.The objectives of the presented study were to identify how the critical process parameters influence the critical quality attributes (CQAs) of a lysozyme-containing multiparticulate dosage form, and to determine the critical points of API activity preservation. The experiments were performed according to a 26 factorial design. The process parameters were recorded with Process Analytical Technology tools, based on in-line mixing speed, mixer torque and temperature measurements and at-line moisture content analysis. The hardness and geometry of the pellets, and the activity of the API were studied as CQA. Complex relationships were identified between the CQAs and process parameters, and the thermomechanical effects and the liquid distribution inside the mass during the texture-forming steps of the process were found to exert considerable effects on the mechanical and geometrical properties and also basically to determine the API activity.

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