Co-Amorphization, Dissolution, and Stability of Quench-Cooled Drug–Drug Coamorphous Supersaturating Delivery Systems with RT-Unstable Amorphous Components

• Published in: Pharmaceutics Vol. 16; no. 12; p. 1488
• Main Authors: Zhang, Yan-Fei, Yao, Qian, Lin, Xiao-Ying, Ma, Ying-Hui, Zhang, Hui-Feng, Yu, Huan, Mu, Shang-Qiang, Zhang, Chuang, Geng, Hao, Hao, Cheng-Yi, Zuo, Li-Li, Wu, Di, Li, Yue, Jin, Li-Li, Shi, Nian-Qiu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2024
• Subjects: Bioavailability; coamorphization and stability; combination therapy; Cooling; Crystallization; Drug delivery systems; Drug therapy, Combination; Drugs; Football (College); Free electron lasers; Pharmaceuticals; quench cooling; Quenching; Spectrum analysis; supersaturating drug delivery systems (SDDS); Vehicles; “drug–drug” coamorphous system (ddCAM); China; supersaturating drug delivery systems (SDDS); “drug–drug” coamorphous system (ddCAM); combination therapy; coamorphization and stability; quench cooling
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics16121488

Background: Supersaturating drug delivery systems (SDDSs) have gained significant attention as a promising strategy to enhance the solubility and bioabsorption of Biopharmaceutics Classification System (BCS) II drugs. To overcome challenges associated with polymer-based amorphous SDDS (aSDDS), coamorphous (CAM) systems have emerged as a viable alternative. Among them, “drug-drug” CAM (ddCAM) systems show considerable potential for combination drug therapy. However, many drugs in their pure amorphous forms are unstable at room temperature (RT), complicating their formation and long-term stability profiles. Consequently, limited knowledge exists regarding the behavior of ddCAMs containing RT-unstable components formed via quench cooling. Methods: In this study, we used naproxen (NAP), a RT-unstable amorphous drug, in combination with felodipine (FEL) or nitrendipine (NTP), two RT-stable amorphous drugs, to create “FEL-NAP” and “NTP-NAP” ddCAM pairs via quench cooling. Our work used a series of methods to perform a detailed analysis on the co-amorphization, dissolution, solubility, and stability profiles of ddCAMs containing RT-unstable drugs, contributing to advancements in co-amorphization techniques for generating SDDS. Results: This study revealed that the co-amorphization and stability profiles of ddCAMs containing RT-unstable components produced via a quench-cooling method were closely related to drug-drug pairing types and ratios. Both quench-cooling and incorporation into coamorphous systems improved the dissolution, solubility, and physical stability of individual APIs. Conclusions: Our findings provide deeper insight into the co-amorphization, dissolution, and stability characteristics of specific drug-drug coamorphous systems FEL-NAP and NTP-NAP, offering valuable guidance for developing new ddCAM coamorphous formulations containing some RT-unstable drugs.