Improved Solubility and Dissolution Rates in Novel Multicomponent Crystals of Piperine with Succinic Acid

Erizal Zaini,Lili Fitriani,Friardi Ismed,Ayano Horikawa,Hidehiro Uekusa,Afriyani Afriyani

doi:10.3390/scipharm88020021

Erizal Zaini, Lili Fitriani + Show 4 more

Open Access

https://doi.org/10.3390/scipharm88020021

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Abstract

The objectives of this study were to prepare and characterize a novel piperine–succinic acid multicomponent crystal phase and to evaluate the improvement in the solubility and dissolution rate of piperine when prepared in the multicomponent crystal formation. The solid-state characterization of the novel multicomponent crystal was performed by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform-infrared (FT-IR) spectroscopy. Solubility and dissolution rate profiles were evaluated in distilled water. The physical stability was evaluated under high relative humidity (75% and 100% RH). The determination of the single crystal X-ray diffraction structure revealed that this novel multicomponent crystal was a cocrystalline phase of piperine–succinic acid (2:1 molar ratio). The differential scanning calorimetry thermogram of the cocrystal showed a single and sharp endothermic peak at 110.49 °C. The cocrystal resulted in greater solubility and a faster dissolution rate of piperine than intact piperine. This improvement was a result of the formation of a channel structure in the cocrystal. In addition, the cocrystal was stable under a humid condition.

Highlights

Piperine is a major secondary metabolite isolated from plants of the Piperaceae family, especially from Piper nigrum L., which is known as the king of spices
Multicomponent crystals between two solid phases are confirmed when the Powder X-ray diffraction (PXRD) pattern of the solid shows a unique pattern that differs from its starting materials
The diffraction pattern of intact piperine showed distinct and sharp diffraction peaks at 2θ values of 14.91◦, 19.68◦, 22.50◦, 25.85◦, and 28.25◦, indicating a solid form with a highly crystalline nature. This PXRD pattern indicated that piperine crystal was of form I

Summary

Introduction

Piperine is a major secondary metabolite isolated from plants of the Piperaceae family, especially from Piper nigrum L., which is known as the king of spices. These species are cultivated in tropical regions, such as Indonesia, Brazil, and India [1,2]. Piperine has been used as a bioenhancer when coadministered with some active pharmaceutical ingredients, such as rapamycin, curcumin, domperidone, and anti-tuberculosis drugs [13,14,15,16]. The pharmaceutical application of piperine is limited by its low solubility in aqueous medium. Water-soluble drugs have low bioavailability; dissolution is the rate-limiting step in the absorption process in the gastrointestinal tract fluid.

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