Characterization of the Dissolution Behavior of Piperine/Cyclodextrins Inclusion Complexes

Abstract

In this study, the physicochemical properties and solubility of inclusion complexes of ground mixtures (GMs) of piperine (PP), a pungent ingredient of pepper, with α- and γ-cyclodextrin (CD) were studied. From the solubility results, the PP/αCD inclusion molar ratio was determined to be 1/2, while that of PP/γCD was 1/1, according to the A-type phase diagram of PP/αCD and the B-type one of PP/γCD. The powder X-ray diffraction and differential scanning calorimetry analyses confirmed the formation of GM complexes with molar ratios of PP/αCD = 1/2 and PP/γCD = 1/1. The Raman analysis revealed the disappearance of the bands corresponding to the C=C, O-CH-O, -CH, and aliphatic C=C moieties of the methylene dioxyphenyl fragment of PP in the spectra of the inclusion complexes. In the dissolution tests, GM (PP/αCD = 1/2) and GM (PP/γCD = 1/1) showed higher solubility than free PP and the analogous physical mixtures. Furthermore, after 60 min, GM (PP/αCD = 1/2) exhibited higher solubility than GM (PP/γCD = 1/1). In the H-H nuclear Overhauser effect spectroscopy measurements, GM (PP/αCD = 1/2) was found to present a head-to-head inclusion structure via the aliphatic C=C and methylene dioxyphenyl groups of PP and the two αCD molecules. In contrast, it was confirmed that γCD interacts with the O-CH-O functionality of the methylene dioxyphenyl group of PP in a molar ratio of 1/1. It was thus concluded that the differences in the PP/CD structures influence the solubility of the inclusion complexes.

Formulation and Evaluation of Supramolecular Food-Grade Piperine HP β CD and TPGS Complex: Dissolution, Physicochemical Characterization, Molecular Docking, In Vitro Antioxidant Activity, and Antimicrobial Assessment

“…The study was performed as per the procedure with the paddle method in the 16th edition of the Japanese Pharmacopoeia. The dissolution medium (water, 900 mL) was used at a temperature of 37 ± 0.5 °C with 50 rpm [ 5 ]. The samples containing PIP (~5 mg) were placed into the dissolution medium.…”

“…It also has an antimicrobial and antiparasitic effect [ 4 ]. Due to its poor solubility, its application as a functional ingredient is limited [ 5 ].…”

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

“…Efforts to improve the solubility and dissolution rates of piperine have been investigated, including the development of a solid dispersion system with several polymers and water-soluble carriers [20,21], the formation of inclusion complexes with cyclodextrin [22][23][24], and the reduction of the particle size to nanoscale [25][26][27]. Although these methods have improved the solubility of piperine, some problems remain.…”

Syntheses and crystal structures of two piperine derivatives

“…As part of our studies in this area, we have already reported a complex using the poorly water-soluble piperine (log P = 2.25) and the cyclic polysaccharide cyclodextrin (Szejtli, 1998;Ezawa et al, 2016). In addition, piperine has been evaluated for its inclusion mechanism and dissolution properties using various cyclodextrins (Ezawa et al, 2018(Ezawa et al, , 2019. The synthesis of piperine derivatives was necessary to understand the inclusion mechanism of piperine and cyclodextrin and the detailed molecular behaviour of piperine.…”