HME for Solid Dispersions: Scale-Up and Late-Stage Development

Brown, Chad; DiNunzio, James; Eglesia, Michael; Forster, Seth; Lamm, Matthew S.; Lowinger, Michael; Marsac, Patrick J.; McKelvey, Craig A.; Meyer, Robert; Schenck, Luke; Terife, Graciela; Troup, Gregory M.; Smith‐Goettler, Brandye; Starbuck, Cíndy

doi:10.1007/978-1-4939-1598-9_7

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…Beyond the primary process parameters, alternative-scale independent factors have been proposed to allow for comparison of screw designs and to aid scale-up for amorphous solid dispersion processing with twin-screw extrusion [52], emphasizing thermal energy, related to temperature in the processing zones, mechanical energy imparted by the screws, and the amount of material in the process zone as mass throughput or fill level in the extruder. For twin-screw wet granulation [53], thermal energy input is generally low and therefore not considered though mechanical energy input and fill were critical.…”

Section: Granulation Process Analysismentioning

confidence: 99%

Continuous Melt Granulation for Taste-Masking of Ibuprofen

Forster

Lebo

2021

Pharmaceutics

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Taste-masking of drugs, particularly to produce formulations for pediatric patients, can be challenging and require complex manufacturing approaches. The objective of this study was to produce taste-masked ibuprofen granules using a novel process, twin-screw melt granulation (TSMG). TSMG is an emerging, high-productivity, continuous process. Granules of ibuprofen embedded in a lipid matrix were produced across a range of process conditions, resulting in a range of output granule particle sizes. The ibuprofen appeared to be miscible with the lipid binder though it recrystallized after processing. The ibuprofen melt granules were tested in simulated saliva using a novel, small-volume dissolution technique with continuous acquisition of the ibuprofen concentration. The ibuprofen release from the granules was slower than the neat API and physical blend, beyond the expected residence time of the granules in the mouth. The ibuprofen release was inversely related to the granule size. A Noyes–Whitney dissolution model was used and the resulting dissolution rate constants correlated well with the granule size.

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Section: Granulation Process Analysismentioning

confidence: 99%

Continuous Melt Granulation for Taste-Masking of Ibuprofen

Forster

Lebo

2021

Pharmaceutics

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“…Its unique blending geometry promotes highly localized shear force that enables drug molecules to dissolve and/or disperse in molten polymers (Haser et al, 2016). HME is high throughput, continuous, and systematically able to be scaled up (Repka et al, 2013);(Brown et al, 2014). It can be developed into a continuous manufacturing platform with the application of Quality by Design (QbD) and Process Analytical Technology (PAT) real time monitoring (Islam et al, 2015, Vo et al.…”

Section: Introductionmentioning

confidence: 99%

Dual mechanism of microenvironmental pH modulation and foam melt extrusion to enhance performance of HPMCAS based amorphous solid dispersion

Feng

Zhang

et al. 2018

International Journal of Pharmaceutics

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Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is an excellent polymeric carrier for melt extrusion amorphous solid dispersion. However, its pH-dependent solubility limits its application, especially for narrow absorption window drugs. The current study proposed a novel dual approach of foam extrusion and microenvironmental pH modulation to overcome this limitation. Sodium bicarbonate was used as a blowing agent and the remaining sodium carbonate acted as an internal pH modifier. Compared with conventional extrusion, foam extrusion dramatically lowered the extrudate physical strength (breaking force and hardness decreased by 20-fold; breaking energy and deformation energy decreased by >30-fold). Milling efficiency of foam extrudate was largely improved compared with that of conventional extrudates, demonstrating smaller particle size, larger specific surface area, and ability to pass through a smaller milling screen. The foam extrudate could generate a supersaturation concentration up to 8-fold higher than the solubility of the pure drug. It also significantly enhanced drug dissolution in a two-step biorelevant medium (p < 0.05). This novel approach improved both manufacturing processability and dissolution of HPMCAS-based solid dispersions.

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