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.

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SUsnic acid is the secondary metabolite found in lichens, particularly Usnea sp which has considerable pharmacological activities. However, the used of usnic acid is still limited due to poorly soluble in water. The aim of this study was to investigate the impact of milling process to physicochemical properties of usnic acid. Usnic acid was isolated from Usnea sp by soxhlet extraction method. The crystal of usnic acid was then milled in three different times: 30, 60 and 90 minutes. The characterization of intact and milled usnic acid were conducted using powder X-ray diffraction (PXRD), infra-red spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Solubility test was conducted in water for 24 h and the amount of usnic acid was determined by UV spectrophotometry. The X-ray diffractogram showed a decline in peak intensity of usnic acid after milling process. The infra-red spectrum showed no shift of wavenumber of usnic acid after milling process. Thermal analysis showed a decline in melting point and heat energy of usnic acid after milling process. The photomicrograph of SEM depicted the changes in habit crystal of milled usnic acid. The solubility of intact usnic acid was 51 µg/ml, while the milled usnic acid increased fourfold compared to intact usnic acid. There was no significant difference of milling time on solubility (p>0.05). In conclusion, the milling process influence the physicochemical properties of usnic acid which indicated by crystallinity, melting point, crystal habit and solubility.

Piperine, a secondary metabolite of Piper nigrum L., has been known for its pharmacological activities. However, the use of piperine is still limited due to the low solubility in water. The aim of this study was to improve the physicochemical properties of piperine by preparing into multicomponent crystal (MC) using saccharin by solvent evaporation method, and ethanol was used as the solvent. The intact materials and MC were characterized by several solid-state instruments. The amount of dissolved piperine was determined by High Performance of Liquid Chromatography (HPLC) using acetonitrile: water (90:10) as the mobile phase. Both morphology of intact piperine and MC showed irregular crystals. The diffractogram showed that MC had new and specific peaks at 2Ɵ: 12.91, 15.04, 19.54 and 22.40. The thermogram presented melting point for intact piperine, saccharin and MC which were 132.81°C, 230.02°C, 197.09°C, respectively. The infra-red spectrum showed no significant shift of MC which indicated no chemical interaction between piperine and saccharin. The dissolution study pointed higher amount of piperine dissolved in 0.1 N HCl with addition of 0.5% sodium lauryl sulphate. The dissolution piperine in MC after 60 minutes was 81.29±5.91%, while intact piperine was 44.78±1.89%. In conclusion, the formation of multicomponent crystal of piperine-saccharin was able to increase the dissolution of piperine.