Probing the Molecular-Level Interactions in an Active Pharmaceutical Ingredient (API) - Polymer Dispersion and the Resulting Impact on Drug Product Formulation

Yang, Fengyuan; Su, Yongchao; Small, James D.; Huang, Chengbin; Martin, Gary E.; Farrington, Andrew M.; DiNunzio, James; Brown, Chad

doi:10.1007/s11095-020-02813-z

Cited by 9 publications

(2 citation statements)

References 81 publications

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“…Using hot-melt extrusion with sustained-release polymers that are not ionizable, in this case, Eudragit RL and RS offer the ability to tailor the release of the API to the therapeutic indication through a combination of particle size and polymer choice while providing robustness over a range of hydrodynamic conditions. The results from this study confirm the ability to adapt the dissolution performance of sustained-release hot-melt extrudates by changing the particle size (and hence the surface area) [ 58 , 59 , 60 , 61 ] or modifying the composition of the extrudates [ 2 , 3 , 35 , 36 ].…”

Section: Discussionsupporting

confidence: 65%

“…The maximum drug load capacity of Eudragit RS for flurbiprofen seems to be around 25% (m/m) drug load, while the maximum drug load capacity of Eudragit RL for flurbiprofen appears to be higher than 35% (m/m). In a solid dispersion, the interaction between polymer and API mainly proceeds through ionic interactions, van der Waals forces and/or hydrogen bonds [ 58 ]. As the amount of ammonium groups in Eudragit RL is twice as high as in Eudragit RS, more interactions between the API and Eudragit RL are possible, which may explain the higher drug load capacity of Eudragit RL.…”

Section: Discussionmentioning

confidence: 99%

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Factors That Influence Sustained Release from Hot-Melt Extrudates

Mansuroglu

Dressman

2023

Pharmaceutics

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Hot-melt extrusion is a well-established tool in the pharmaceutical industry, mostly implemented to increase the solubility of poorly soluble drugs. A less frequent application of this technique is to obtain formulations with extended release. This study investigated the influence of polymer choice, drug loading, milling and hydrodynamics on the release of a model drug, flurbiprofen, from sustained-release hot-melt extrudates with Eudragit polymers. The choice of polymer and degree of particle size reduction of the extrudate by milling were the two key influences on the release profile: the percentage release after 12 h varied from 6% (2 mm threads) to 84% (particle size <125 µm) for Eudragit RL extrudates vs. 4.5 to 62% for the corresponding Eudragit RS extrudates. By contrast, the release profile was largely independent of drug loading and robust to hydrodynamics in the dissolution vessel. Thus, hot-melt extrusion offers the ability to tailor the release of the API to the therapeutic indication through a combination of particle size and polymer choice while providing robustness over a wide range of hydrodynamic conditions.

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