Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures

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• 作者：Sharad Mangal^a ; Felix Meiser^a ; Geoffrey Tan^a ; Thomas Gengenbach^b ; David A.V. Morton^a ; Ian Larson^a ; ^{Ian.Larson@monash.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Polyvinylpyrrolidone ; l-Leucine ; Cohesion&ndash ; adhesion balance ; Paracetamol ; Surface energy ; Work of cohesion ; Work of adhesion ; High-dose API ; Direct compression ; Flow ; Compactibility
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：104
• 期：Complete
• 页码：110-116
• 全文大小：2181 K

文摘

In this study, we investigated the applicability of cohesive–adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends.

Methods

Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (w_co$w_{\mathit{co}}$) and work of adhesion (w_ad$w_{\mathit{ad}}$) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised.

Results

The surface-energy derived work of adhesion (w_ad$w_{\mathit{ad}}$) between excipient and paracetamol particles increased, while the corresponding work of cohesion (w_co$w_{\mathit{co}}$) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (w_co>w_ad$w_{\mathit{co}}>w_{\mathit{ad}}$), small excipient particles were apparent as agglomerates. For excipients with 5% and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (w_ad⩾w_co$w_{\mathit{ad}}⩾w_{\mathit{co}}$) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5% (w/w) excipient proportions, blends for which w_ad⩾w_co$w_{\mathit{ad}}⩾w_{\mathit{co}}$ demonstrated higher compactibility than other blends. Furthermore, at 10% (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends.

Conclusion

In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.