Over-blending effect of lubricants on capsules manufacturing: a simple and fast wettability technique to predict batch dissolution performance

Abstract

Mixing/blending is a crucial operation in the manufacturing of solid drug products in the pharmaceutical industry. Although usually described and controlled in specific steps, blending is also inherent to other operations such as the transference of materials and equipment feeding systems. This study aimed to investigate a simple and fast wettability testing procedure capable to foresee the potential over-blending effects of lubricants occurring during the manufacturing of solid dosage forms. An industrial batch blend was submitted to two mixing mechanisms studies (diffusion and shear) during increasing time periods, and the developed wettability testing procedure was applied to assess their impact on blend water uptake. Capsules filled with these blends were tested for dissolution and disintegration. The method was applied to capsules with known dissolution results manufactured at an industrial scale. Results demonstrated that processes inducing shear stress led to less permeable blends with consequent retardation on capsules dissolution of at least 35% in the tested timepoints and obtained study metrics above 500 s. Moreover, disintegration testing was not able to detect non-compliant dissolutions, while the proposed wettability testing procedure proved to be able to identify performance failures. Wettability results correlate the effect of mixing mechanisms to capsules dissolution performance, evidencing that this technique can be applied in the pharmaceutical industry to evaluate possible over-blending effects.

Keywords:

• Dissolution
• magnesium stearate
• over-blending
• mixing mechanisms
• wettability

Acknowledgments

This work had the collaboration of Pharmaceutical Sciences of BIAL – Portela & C^a, S.A., Avenida da Siderurgia Nacional, 4745-457 Trofa, Portugal.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.