Insights into tablet sticking: a quantitative case study with an ibuprofen and methocarbamol-based formulation

Area of Science:

• Pharmaceutical manufacturing
• Materials science
• Process engineering

Background:

• Tablet sticking, the accumulation of pharmaceutical powder on tooling, negatively impacts tablet production and quality.
• Previous research introduced multivariate data analysis for understanding tablet sticking in industrial settings.
• The current study builds upon prior work to quantitatively predict punch sticking intensity.

Purpose of the Study:

• To generalize a multivariate data analysis approach for predicting tablet sticking.
• To quantitatively assess punch sticking intensity based on formulation and process variables.
• To identify key factors influencing tablet sticking in ibuprofen and methocarbamol formulations.

Main Methods:

• Utilized Partial Least Squares (PLS) regression models.
• Collected 345 variables from 28 industrial batches of a specific drug formulation.
• Applied statistical validation techniques, including Shapiro-Wilks test and R-squared analysis.

Main Results:

• Granulation duration and compression force were identified as significant factors explaining approximately 60% of sticking variations.
• PLS regression models demonstrated a strong association between these factors and sticking intensity.
• Validation residues were normally distributed (p=0.96) and independent of the target variable (R²=9.5%), indicating model robustness.

Conclusions:

• The generalized multivariate approach effectively predicts quantitative punch sticking intensity.
• Granulation duration and compression force are critical parameters for controlling tablet sticking.
• The findings offer valuable insights for optimizing pharmaceutical tablet manufacturing processes.