A formulation strategy for solving the overgranulation problem in high shear wet granulation.

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• High shear wet granulation (HSWG) often leads to overgranulation, reducing tablet strength.
• Overgranulation impairs the ability to form adequately strong tablets.

Purpose of the Study:

• To investigate if incorporating brittle excipients into a plastic matrix can mitigate overgranulation in HSWG.
• To evaluate the impact of brittle excipients on granule fracture and tablet mechanical strength.

Main Methods:

• Formulation of granules using microcrystalline cellulose (MCC) as a plastic matrix with varying concentrations of brittle excipients (lactose or dibasic calcium phosphate).
• Assessment of tabletability and tablet tensile strength at different granulating water levels.
• Microscopic analysis (scanning electron microscope) to examine granule fracture and bonding.

Main Results:

• Plastic MCC alone showed a complete loss of tabletability with increased granulating water (≥ 55%).
• Incorporating lactose or dibasic calcium phosphate improved tabletability in a concentration-dependent manner.
• Tablet tensile strength showed a minimum with increasing granulating water, but remained higher with brittle excipients.

Conclusions:

• The addition of brittle excipients to a plastic matrix is an effective strategy to combat overgranulation in HSWG.
• Brittle fracture of granules, promoted by brittle excipients, increases the bonding area and enhances tablet mechanical strength.
• This approach offers a viable solution for improving the robustness of granules produced via HSWG.