Development of Spray-Dried Co-crystals of Piperine and Succinic Acid for Solubility Enhancement

Piperine (PIP) is an amide alkaloid that belongs to the biopharmaceutical classification system II and shows poor aqueous solubility, which limits its therapeutic efficacy. To counter this issue, the objective of the current research was to screen and prepare co-crystals of piperine using succinic acid as a co-former in different molar ratios. Since spray drying is a well-known scale-up technology for co-crystallization, it has been used in the current research for co-crystal preparation. This study aimed at enhancing solubility and dissolution rate by preparing piperine co-crystals. Equimolar ratios of piperine and succinic acid were used to prepare co-crystals via spray drying. The developed spray-dried co-crystals were characterized by in silico modeling, solubility studies, in vitro dissolution studies, Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). PXRD studies of spray-dried co-crystals showed improved crystallinity, SEM studies revealed a distinct morphology compared to parent components, and the DSC thermogram indicated enhanced thermal stability. The solubility of piperine at pH 7.4 (19.2 ± 1.23 µg/mL) and pH 1.2 (35.2 ± 0.16 µg/mL) increased by almost 2-3 times which was 49.5 ± 0.89 µg/mL at pH 7.4 and 96.4 ± 1.62 µg/mL at pH 1.2. Increasing the concentration of succinic acid improves the solubility of PIP. Moreover, compared to pure piperine, the dissolution rate of piperine co-crystals increased by almost threefold. This increase may be due to the strong hydrogen bonding of piperine and succinic acid in co-crystals. The stability of piperine was also improved as the co-crystals remained stable under accelerated temperature and humidity conditions. Our findings conclude that prepared spray-dried co-crystals have the potential to improve the solubility and dissolution profile of piperine. Hence, co-crystals can be a suitable approach for improving the physicochemical properties of BCS Class II drugs.