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Co-Amorphization, Dissolution, and Stability of Quench-Cooled Drug-Drug Coamorphous Supersaturating Delivery Systems
Yan-Fei Zhang1, Qian Yao2, Xiao-Ying Lin1
1School of Pharmacy, Jilin Medical University, Jilin 132013, China.
Pharmaceutics
|January 8, 2025
Summary
Drug-drug coamorphous systems (ddCAMs) containing room temperature-unstable drugs were successfully formed using quench cooling. These systems enhanced drug solubility, dissolution, and stability, offering new formulation possibilities.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Materials Science
Background:
- Supersaturating drug delivery systems (SDDSs) are crucial for enhancing solubility and bioabsorption of Biopharmaceutics Classification System (BCS) class II drugs.
- Coamorphous (CAM) systems, particularly drug-drug CAM (ddCAM), offer an alternative to polymer-based amorphous SDDS (aSDDS) for combination therapy.
- The stability of amorphous drugs at room temperature (RT) poses challenges for forming and maintaining ddCAMs, with limited research on RT-unstable components.
Purpose of the Study:
- To investigate the co-amorphization, dissolution, solubility, and stability of ddCAMs containing RT-unstable components formed via quench cooling.
- To explore the formation of "FEL-NAP" and "NTP-NAP" ddCAM pairs using naproxen (NAP) as the RT-unstable component.
Main Methods:
- Preparation of "FEL-NAP" and "NTP-NAP" drug-drug coamorphous systems using the quench-cooling method.
- Comprehensive analysis of co-amorphization, dissolution, solubility, and physical stability profiles of the prepared ddCAMs.
- Utilized various analytical techniques to characterize the ddCAMs containing RT-unstable naproxen.
Main Results:
- Co-amorphization and stability of ddCAMs with RT-unstable components depend on drug pairing and ratios when using quench cooling.
- Both quench cooling and coamorphous system formation improved the dissolution, solubility, and physical stability of individual active pharmaceutical ingredients (APIs).
- Successful formation of FEL-NAP and NTP-NAP ddCAMs demonstrated the feasibility of incorporating RT-unstable drugs.
Conclusions:
- The study provides insights into the co-amorphization, dissolution, and stability of FEL-NAP and NTP-NAP ddCAMs.
- Findings guide the development of novel ddCAM formulations containing room temperature-unstable drugs.
- Quench cooling is an effective method for creating stable ddCAMs with improved drug properties.
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