RESUMEN

Simultaneous micronization and purification of DLBS3233 bioactive fraction, a combination of two Indonesian herbals Lagerstroemia speciosa and Cinnamomum burmannii has been successfully performed via supercritical anti-solvent (SAS) technology. The objective of the present study was to investigate the effectiveness of SAS technology to micronize and reduce coumarin content of DLBS3233. The effects of four SAS process parameters, i.e. pressure, temperature, concentration and solution flow rate on particle formation were investigated. In SAS process, DLBS3233 was dissolved in dimethylformamide (DMF) as the liquid solvent. The solution was then pumped through a nozzle into a chamber simultaneously with supercritical carbon dioxide (SC-CO2) which acts as the anti-solvent, resulting in DLBS3233 precipitation. Physicochemical properties of unprocessed DLBS3233 and SAS-processed DLBS3233 particles were analyzed using scanning electron microscopy (SEM) and high pressure liquid chromatography (HPLC). Total polyphenol content (TPC) was also analyzed. Particles with mean particle size ranging from 0.107±0.028 µm to 0.298±0.138 µm were obtained by varying the process parameters. SAS-processed DLBS3233 particles showed no coumarin content in all experiments studied in this work. Results of TPC analysis revealed no significant change in SAS-processed DLBS3233 particles compared to unprocessed DLBS3233. Nano-sized DLBS3233 particles with no coumarin content have been successfully produced using SAS process. This study demonstrates the ability of SAS for processing herbal medicine in single step process.

RESUMEN

We report novel pharmaceutical salts of an anti-hypertensive drug carvedilol (CVD) with pharmaceutically acceptable salt formers, including oxalic acid (OXA), fumaric acid (FUMA), benzoic acid (BZA), and mandelic acid (MDA) via conventional solvent evaporation technique. The pKa difference between CVD and selected acids was greater than 3, thus suggesting salt formation. Two polymorphic forms of CVD/MDA salts and one p-Dioxane solvate of CVD/FUMA salt were also reported in this paper. The salts were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Stability of the salts was assessed by storage at 40°C/75% RH for 1 month. All CVD salts exhibited higher solubility in phosphate buffer solution pH 6.8 compared to the parent drug CVD and showed good stability in accelerated ICH conditions at 40°C/75% RH for 1 month. CVD/FUMA salt showed the highest solubility (1.78 times). Based on thermal analysis and slurry experiment, it was found that CVD/MDA polymorphs were related monotropically with Form 1 as the stable form. The results suggested that salt formation could be an alternative method to improve CVD solubility.

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RESUMEN

We report novel pharmaceutical cocrystal of a popular antipyretic drug paracetamol (PCA) with coformer 5-nitroisophhthalic acid (5NIP) to improve its tabletability. The cocrystal (PCA-5NIP at molar ratio of 1:1) was synthesized by solvent evaporation technique using methanol as solvent. The physicochemical properties of cocrystal were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), fourier transform infrared spectroscopy (FTIR), hot stage polarized microscopy (HSPM) and scanning electron microscopy (SEM). Stability of the cocrystal was assessed by storing them at 40°C/75% RH for one month. Compared to PCA, the cocrystal displayed superior tableting performance. PCA-5NIP cocrystal showed a similar dissolution profile as compared to PCA and exhibited good stability. This study showed the utility of PCA-5NIP cocrystal for improving mechanical properties of PCA.

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