In Situ Salt Formation during Reactive Melt Extrusion Improve the Dissolution Rate and Physical Stability of Naproxen Amorphous Solid Dispersions

2016 ◽  
Author(s):  
Xu Liu
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Salt Formation ◽  
Melt Extrusion ◽  
Amorphous Solid Dispersions ◽  
Reactive Melt

scholarly journals Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 655
Author(s):  
Wei Qiang ◽  
Korbinian Löbmann ◽  
Colin P. McCoy ◽  
Gavin P. Andrews ◽  
Min Zhao
Keyword(s):  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Downstream Processing ◽  
Amorphous Solid Dispersions ◽  
New Strategy ◽  
Amorphous Drugs ◽  
Stability Issue ◽  
Underlying Mechanisms

The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

scholarly journals Rapid Assessment of the Physical Stability of Amorphous Solid Dispersions

2017 ◽  
Vol 17 (5) ◽  
pp. 2478-2485 ◽  
Author(s):  
Pinal Mistry ◽  
Kweku K. Amponsah-Efah ◽  
Raj Suryanarayanan
Keyword(s):  
Solid Dispersions ◽  
Rapid Assessment ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

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.

Sign in / Sign up

Export Citation Format

Share Document