期刊
MOLECULAR PHARMACEUTICS
卷 10, 期 6, 页码 2381-2393出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp400029v
关键词
crystal growth; cellulose polymers; supersaturation; hydrophobicity; specific intermolecular interactions; amorphous formulation
资金
- National Science Foundation [DMR-0804609]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [0804609] Funding Source: National Science Foundation
The presence of an effective crystal growth inhibitor in solution is desirable to prolong supersaturation since residual crystalline material in an amorphous formulation resulting from the manufacturing process or formed during storage or dissolution can potentially have a significant impact on the extent and duration of supersaturation. In this study, the effectiveness of a group of chemically diverse polymers, including several recently synthesized cellulose derivatives, on solution crystal growth of three structurally diverse compounds (celecoxib, efavirenz, and ritonavir) was quantified at different extents of supersaturation and compared. Despite the different chemical properties and structures of the model compounds, nonspecific hydrophobic drug-polymer interactions appeared to be important in determining the impact of a given polymer on crystal growth for of all these drug compounds. Specific intermolecular interactions were also found to be important for crystal growth inhibition of celecoxib and efavirenz by the hydrophilic polymer, PVPVA. These interactive forces-hydrophobicity and specific intermolecular interactions-are likely to promote adsorption of the polymer onto the surface of the crystalline drugs, thus influencing crystal growth. The effectiveness of the polymers also depended on the rate of crystallization of the drug molecules. At a similar supersaturation ratio of similar to 1.2, ritonavir and celecoxib had slower normalized crystal growth rates (0.20 and 0.91 mg min(-1) m(-2), respectively), while the normalized crystal growth rate of efavirenz was significantly higher (2.97 mg min(-1) m(-2)), resulting in lower levels of crystal growth inhibition by the polymers for efavirenz.
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