Acid-base interactions in amorphous solid dispersions of lumefantrine prepared by spray-drying and hot-melt extrusion using X-ray photoelectron spectroscopy

2016 ◽  
Vol 514 (2) ◽  
pp. 456-464 ◽  
Author(s):  
Yang Song ◽  
Dmitry Zemlyanov ◽  
Xin Chen ◽  
Ziyang Su ◽  
Haichen Nie ◽  
...  
Keyword(s):  
Spray Drying ◽  
Photoelectron Spectroscopy ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Melt Extrusion ◽  
Acid Base ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
Hot Melt

scholarly journals Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1307
Author(s):  
Yongjun Li ◽  
Amanda K. P. Mann ◽  
Dan Zhang ◽  
Zhen Yang
Keyword(s):  
Spray Drying ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Drug Solubility ◽  
Melt Extrusion ◽  
Amorphous Solid Dispersions ◽  
Hot Melt

Presently, a large number of drug molecules in development are BCS class II or IV compounds with poor aqueous solubility. Various novel solubilization techniques have been used to enhance drug solubility. Among them, amorphous solid dispersions (ASD), which convert a crystalline drug into an amorphous mixture of drug and polymer, have been demonstrated to be an effective tool in enhancing drug solubility and bioavailability. There are multiple ways to produce amorphous solid dispersions. The goal of the present study is to investigate two commonly used processing methods, hot-melt extrusion (HME) and spray drying, and their impact on drug bioperformance. The amorphous solid dispersions of a model compound, posaconazole (25% drug loading) in HPMCAS-MF, were successfully manufactured via the two processing routes, and the physicochemical properties, in vitro and in vivo performance of the resulting ASDs were characterized and compared. It was found that in vitro drug release of the ASDs from two-stage dissolution was significantly different. However, the two ASDs showed similar in vivo performance based on cynomolgus monkey PK studies. A mechanistic understanding of the in vitro and in vivo behaviors of the solid dispersions was discussed.

scholarly journals Influence of Carbamazepine Dihydrate on the Preparation of Amorphous Solid Dispersions by Hot Melt Extrusion

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 379 ◽  
Author(s):  
Xiangyu Ma ◽  
Felix Müller ◽  
Siyuan Huang ◽  
Michael Lowinger ◽  
Xu Liu ◽  
...  
Keyword(s):  
Energy State ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Amorphous Solid Dispersions ◽  
Water Soluble Drugs ◽  
The Impact ◽  
Hot Melt

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.

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