Application of Hot Melt Extrusion for Poorly Water-Soluble Drugs: Limitations, Advances and Future Prospects

2014 ◽  
Vol 20 (3) ◽  
pp. 369-387 ◽  
Author(s):  
Ming Lu ◽  
Zhefei Guo ◽  
Yongcheng Li ◽  
Huishi Pang ◽  
Ling Lin ◽  
...  
2011 ◽  
Vol 79 (2) ◽  
pp. 372-381 ◽  
Author(s):  
Christoph Kindermann ◽  
Karin Matthée ◽  
Jutta Strohmeyer ◽  
Frank Sievert ◽  
Jörg Breitkreutz

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 379 ◽  
Author(s):  
Xiangyu Ma ◽  
Felix Müller ◽  
Siyuan Huang ◽  
Michael Lowinger ◽  
Xu Liu ◽  
...  

Amorphous solid dispersions (ASDs) are commonly used in the pharmaceutical industry to improve the dissolution and bioavailability of poorly water-soluble drugs. Hot melt extrusion (HME) has been employed to prepare ASD based products. However, due to the narrow processing window of HME, ASDs are normally obtained with high processing temperatures and mechanical stress. Interestingly, one-third of pharmaceutical compounds reportedly exist in hydrate forms. In this study, we selected carbamazepine (CBZ) dihydrate to investigate its solid-state changes during the dehydration process and the impact of the dehydration on the preparation of CBZ ASDs using a Leistritz micro-18 extruder. Various characterization techniques were used to study the dehydration kinetics of CBZ dihydrate under different conditions. We designed the extrusion runs and demonstrated that: 1) the dehydration of CBZ dihydrate resulted in a disordered state of the drug molecule; 2) the resulted higher energy state CBZ facilitated the drug solubilization and mixing with the polymer matrix during the HME process, which significantly decreased the required extrusion temperature from 140 to 60 °C for CBZ ASDs manufacturing compared to directly processing anhydrous crystalline CBZ. This work illustrated that the proper utilization of drug hydrates can significantly improve the processability of HME for preparing ASDs.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 692 ◽  
Author(s):  
Hui-Won Cho ◽  
Seung-Hoon Baek ◽  
Beom-Jin Lee ◽  
Hyo-Eon Jin

Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.


2007 ◽  
Vol 336 (1) ◽  
pp. 22-34 ◽  
Author(s):  
James E. Patterson ◽  
Michael B. James ◽  
Angus H. Forster ◽  
Robert W. Lancaster ◽  
James M. Butler ◽  
...  

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