The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes. Water-soluble cellulosic polymers, including HPMC E15, HPMC E5, HPMC K100-LV, L-HPC, and MC, were studied. All cellulosic polymers could extend API dissolution and solubility to various extents by delaying crystallization and prolonging supersaturation duration, with their effectiveness ranked from greatest to least as HPMC E15 > HPMC E5 > HPMC K100-LV > L-HPC > MC. Decreased polymer amount, lower ionic strength, or higher polymer viscosity tended to decrease dissolution/solubility and promote crystal growth to accelerate crystallization. HPMC E15 achieved greatest extended API dissolution and maintenance of supersaturation from a supersaturated state; this polymer thus had the greatest potential for maintaining sustainable API absorption within biologically relevant time frames.
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This work was supported by Scientific Research Foundation of the Education Department of Jilin Province of China (No. 2015-401), Science and Technology Development Program of Jilin Province of China (Nos. 20160520046JH and 20140203012YY), the National Natural Science Foundation of China (No. 81602654), Science and Technology Development Program of Jilin City in Jilin Province of China (No. 201464053), the State Key Laboratory of Medicinal Chemical Biology of Nankai University (No. 201503001), and China Postdoctoral Science Foundation (No. 2015M571373).
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Shi, N., Jin, Y., Zhang, Y. et al. The Influence of Cellulosic Polymer’s Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State. AAPS PharmSciTech 20, 12 (2019). https://doi.org/10.1208/s12249-018-1266-y
- cellulosic polymers
- amorphous drug
- dissolution/solubility enhancement
- crystallization inhibition
- supersaturated state