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.

BACKGROUND: Trimethoprim is a broad spectrum antimicrobial agent with low solubility in water which causes low bioavailability in systemic circulation. AIM: The purpose of this study was to prepare multicomponent crystals of trimethoprim and citric acid to increase the solubility and dissolution rate of trimethoprim. MATERIALS AND METHODS: Multicomponent crystals were prepared by solvent evaporation method. Characterizations of multicomponent crystalline solid phase properties were carried out by powder X-ray diffraction (PXRD) analysis, differential scanning calorimetry (DSC), FT-IR spectroscopy, scanning electron microscopy (SEM). Solubility and dissolution rate tests were carried out in aqueous medium. RESULTS: The PXRD characterization results showed a new X-ray diffraction pattern in the multicomponent crystal phase. DSC analysis showed the formation of a new endothermic peak. This indicates the formation of a multicomponent crystal phase between trimethoprim and citric acid. The results of the SEM analysis indicate the formation of a new crystal habit. Solubility of multi-component crystal phase of trimethoprim increased 7 times compared to intact trimethoprim. The dissolution of trimethoprim and multicomponent crystals in 0.1 N HCl medium at 60 minutes was 56.36% and 95.57% and CO2-free distilled water medium was 43.03% and 88.26%, respectively. CONCLUSIONS: From the results of the study, it can be concluded that the multicomponent phase of trimethoprim crystals with citric acid successfully increase the solubility and dissolution rate of trimethoprim significantly.

Fenofibric Acid (FA) is classified under Biopharmaceutical Classification System (BCS) class II due to its poorly soluble in water and high permeability. The present study aimed to prepare the eutectic mixture of FA with nicotinic acid (NA) and characterize its solid state properties and in vitro dissolution rate, along with its in vivo antihyperlipidemic activity. Solvent drop grinding was the method chosen to prepare the eutectic mixture of FA and NA. Solid-state properties were evaluated using thermal analysis Differential Scanning Calorimetry (DSC), crystallographic analysis Powder X-Ray Diffraction (PXRD), FT-IR spectroscopic analysis, and Scanning Electron Microscopy (SEM). To examine in vivo antihyperlipidemic activity, 16 male Swiss Webster rats were injected with 1% hyperlipidemia-inducing solution, followed by the oral administration of 9.45 mg/kg FA and NA (equivalent to 9.45 mg/kg FA), after which the decrease in cholesterol levels was measured. Two-way ANOVA was used to evaluate the data, followed by Duncan’s multiple range test (95% confidence interval). The results proved that FA formed the eutectic mixture with NA at a molar ratio of 6:4. The eutectic mixture of FA-NA had a better solubility and in vitro dissolution rate compared to intact FA, which also led to notably improved antihyperlipidemic activity.

Fenofibric acid is a poorly water‐soluble drug with high permeability; thus, it is classified as a Biopharmaceutical Classification System (BCS) class II. This study aimed to prepare a eutectic mixture of fenofibric acid with syringic acid as a coformer to improve its solubility, dissolution rate, and antihyperlipidemic activity. The solvent co‐evaporation method was used to form a eutectic mixture. Solid‐state properties were characterized, solubility and in vitro dissolution profiles were studied, and in vivo antihyperlipidemic effectiveness was investigated in male Wistar rats. The results showed that the eutectic mixture of fenofibric acid‐syringic acid enhanced the solubility (3.4‐fold) and in vitro dissolution rate (3.62‐fold) and significantly improved the antihyperlipidemic activity compared with intact fenofibric acid.

AIM: The aim of this study was to prepare solid dispersion of tenoxicam with hydroxypropyl methylcellulose (HPMC) to improve solubility, dissolution rate, and in vivo analgesic activity. METHODS: Solid dispersion of tenoxicam with HPMC was prepared using the freeze-drying technique in three ratios of drug to carrier (1:1, 1:2, and 2:1 w/w). The s olid-state properties of solid dispersion powders were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, and scanning electron microscope (SEM). Solubility and dissolution rate studies were conducted in an aqueous medium. Analgesic activity was evaluated using the writhing method. RESULTS: Analysis of PXRD and DSC results indicated a decreased degree of crystallinity of tenoxicam in solid dispersion powders. Solid dispersion of tenoxicam exhibited a significant improvement in solubility and dissolution rate compared to intact tenoxicam, in line to the increment on the ratio of HPMC. Analgesic activity study revealed that solid dispersion 1:2 was more effective than intact tenoxicam. CONCLUSIONS: This study concludes that the solid dispersion technique is a promising strategy to improve the solubility and dissolution rate of tenoxicam.