Ibuprofen is classified as a BCS class II drug which has low solubility and high permeability. We conducted the formation of the cocrystalline phase of ibuprofen with coformer nicotinamide to increase its solubility. The purpose of this study was to characterize the solid state of cocrystalline phase of ibuprofen-nicotinamide, determine the solubility, and evaluate its in vivo analgesic activity. The cocrystal of ibuprofen-nicotinamide was prepared by a slow evaporation method. The solid-state characterization was conducted by powder X-ray diffraction (PXRD) analysis, differential thermal analysis (DTA), and scanning electron microscopy (SEM). To investigate the in vivo analgesic activity, 28 male Swiss-Webster mice were injected with acetic acid 0.5% following oral administration of intact ibuprofen, physical mixture, and its cocrystalline phase with nicotinamide (equivalent to 26 mg/kg ibuprofen). The number of writhes was counted, and pain inhibition was calculated. All data were analyzed with one-way ANOVA followed by Duncan’s Multiple Range Test (95% confidence interval). The results revealed that a new cocrystalline phase was successfully formed. The solubility testing showed that the cocrystal formation enhanced the solubility significantly as compared with the physical mixture and intact ibuprofen. A significant increase in the analgesic activity of cocrystal ibuprofen-nicotinamide was also confirmed.

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.

Piperine, the main bioactive compound found in black pepper (Piper nigrum L.), has long been used in Ayurveda and traditional Chinese medicine (TCM). This compound has remarkable potential pharmacological properties, including being anti-inflammatory, antimicrobial, anticancer, anticonvulsant, antidepressant, neuroprotective, and hepatoprotective. Recent studies have reported piperine activity as an antiviral against SARS-CoV-2, which caused COVID-19. Nevertheless, the clinical use of piperine is still limited, due to its poor water solubility and bioavailability; therefore, various approaches have been developed in order to solve these limitations. This review summarises recent studies (i.e. uploaded to electronic databases in the last 10 y) regarding strategies that have been investigated to improve piperine’s solubility and pharmacokinetic properties, using ‘piperine’, ‘solubility’, ‘bioavailability’, and ‘formulation’ as keywords. Articles that have focused on piperine as the main compound were selected and sorted based on their modification and formulation types. Studies reported various approaches: from derivatives and analogue synthesis, crystal engineering, complexation, particle size reduction (micro-and nanonisation), and lipid-and polymer-based drug delivery systems, to inorganic and hybrid nanoparticles. This review also highlights limitations and challenges for these approaches and encourages further studies to optimise piperine’s potential benefits.

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 2Φ: 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.