(M1030-02-13) Prediction and Investigation of the Effect of Binders on the Occurrence of Tablet Sticking by Powder Rheology

Purpose: It has been proved that intermolecular interactions between API and metal surface determine the adhesion tendencies. Current work hypothesizes that the granulation using different binders can affect the extent of adhesion forces between the APIs and metal surfaces and will affect the tablet sticking propensity. The rank order of sticking between APIs/formulations and metal surfaces can be established using powder rheology studies. Powder rheological studies predict the sticking rank order at the molecular and intermolecular levels by considering various powder properties including size, shape, etc. The goal is to prepare powder blends by wet granulation method using varying concentrations of the binders. Predicting the sticking rank order using powder rheological studies and validate it with the compression study.

Methods: Acetaminophen (APAP) and Ketoprofen (KTPF) were used as model drugs, while Hydroxypropyl Cellulose SSL (HPC SSL) and Hydroxypropyl Cellulose L (HPC L) were used as a binder and Magnesium Stearate (MgSt) was used as lubricants in this study. Granules were made by wet granulation method using three different concentrations 2.5 %w/w, 5.0 %w/w and 7.5 %w/w of binders. FT4 powder Rheometer was used to evaluate the degree of adherence specifically Shear cell test (Kinematic angle of Internal Friction (Φ)) which indicates cohesion force and Wall friction test (Angle of Wall Friction (φ)) which indicates adhesion force. The wall friction test was performed on each formulation using five different metal coupons. The five metal surfaces used were S7, M340, Zirconium Nitride (ZrN), Chromium Nitride (CrN), and Hard Chromium (HCr). Sticking index was calculated using following equation: Sticking Index = Angle of Wall Friction (φ) / Kinematic angle of Internal Friction (Φ)

Results: For formulation with HPC L, increase in binder concentration there is increase in the Angle of Internal Friction (Φ), which indicates high cohesion. With high amount of binder wall friction angle is decreasing for most of the metals, which indicates lower adhesion. M340 and HCr coated metal coupon shows least amount of adhesion. ZrN coated metal coupon shows highest adhesion as the angle of wall friction is highest among all 5 metal coupons. Increase in cohesion and decrease in adhesion have positive impact on sticking index. Sticking rank order for each metal was predicted after calculating the sticking index. The sticking rank order was validated with the compression study.

Conclusion: Powder Rheology can be an important tool to predict the sticking propensity as well as in selection of right metal for tooling for the formulation.

Graph: Angle of internal friction

Graph angle of wall friction

Sticking propensity rank order