Co-crystallization is a powerful method to improve the physico-chemical properties of drugs. Loperamide hydrochloride is a topical analgesic for the gastro intestinal tract showing low and pH-dependent solubility, for this reason an enhancement of its solubility and/or dissolution rate, particularly at the pH of the intestinal tract, could improve its local efficacy. Here, we prepared co-crystals of this active principle with glutaric acid, so obtaining a new crystalline solid representing a viable alternative to improve the physico-chemical 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 with 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 co-crystals showed improved water solubility in comparison to loperamide HCl, and the pharmaceutical formulation proposed was able to release the drug more rapidly in comparison to three reference commercial products, when tested at neutral pHs.

An Experimental and Theoretical Investigation of Loperamide Hydrochloride-Glutaric Acid Co-Crystals.

Giovanna Bruni;Mariarosa Maietta;Lauretta Maggi;Piercarlo Mustarelli;Chiara Ferrara;Vittorio Berbenni;Mauro Freccero;SCOTTI, FEDERICO;Chiara Milanese;Alessandro Girella;Amedeo Marini
2013

Abstract

Co-crystallization is a powerful method to improve the physico-chemical properties of drugs. Loperamide hydrochloride is a topical analgesic for the gastro intestinal tract showing low and pH-dependent solubility, for this reason an enhancement of its solubility and/or dissolution rate, particularly at the pH of the intestinal tract, could improve its local efficacy. Here, we prepared co-crystals of this active principle with glutaric acid, so obtaining a new crystalline solid representing a viable alternative to improve the physico-chemical 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 with 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 co-crystals showed improved water solubility in comparison to loperamide HCl, and the pharmaceutical formulation proposed was able to release the drug more rapidly in comparison to three reference commercial products, when tested at neutral pHs.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/691420
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