An Experimental and Theoretical Investigation of Loperamide Hydrochloride-Glutaric Acid Cocrystals

被引：11

作者：

Bruni, Giovanna ^{[1
]}

Maietta, Mariarosa ^{[1
]}

Maggi, Lauretta ^{[2
]}

Mustarelli, Piercarlo ^{[1
]}

Ferrara, Chiara ^{[1
]}

Berbenni, Vittorio ^{[1
]}

Freccero, Mauro ^{[3
]}

Scotti, Federico ^{[1
]}

Milanese, Chiara ^{[1
]}

Girella, Alessandro ^{[1
]}

Marini, Amedeo ^{[1
]}

机构：

[1] Univ Pavia, Phys Chem Sect, CSGI Dept Chem, I-27100 Pavia, Italy

[2] Univ Pavia, Dept Drug Sci, I-27100 Pavia, Italy

[3] Univ Pavia, Organ Chem Sect, Dept Chem, I-27100 Pavia, Italy

来源：

JOURNAL OF PHYSICAL CHEMISTRY B | 2013年 / 117卷 / 27期

关键词：

D O I：

10.1021/jp404273x

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Cocrystallization is a powerful method to improve the physicochemical properties of drugs. Loperamide hydrochloride is a topical analgesic for the gastrointestinal tract showing low and pH-dependent solubility; for this reason, an enhancement of its solubility or dissolution rate, particularly at the pH of the intestinal tract, could improve its local efficacy. Here we prepared cocrystals of this active principle with glutaric acid and so obtained a new crystalline solid representing a viable alternative to improve the physicochemical properties and thus the pharmaceutical behavior of the drug. Differential scanning calorimetry, X-ray powder diffraction, Fourier infrared spectroscopy solid-state NMR, and scanning electron microscopy coupled to the energy-dispersive X-ray spectrometry were used to investigate the new solid-phase, formation. DFT calculations at B3LYP/6-31G(d) level, of theory, in the gas phase, including frequencies computation, Provided a rationale for the interaction between loperamide hydrochloride and glutaric acid. The cocrystals showed improved water solubility in comparison with loperamide HCl, and the pharmaceutical formulation proposed was able to release the drug more rapidly comparison with three reference commercial products when tested at neutral pH values.

引用

页码：8113 / 8121

页数：9

共 17 条

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