The purpose of this work was to explore the formation of ketoprofen-malonic acid cocrystal by solvent evaporation method. Early detection of cocrystal formation was conducted by hot stage microscopy and solid-liquid phase diagram. Cocrystal were prepared by solvent evaporation method by using isopropyl alcohol as solvent. Characterization of cocrystal was done by Powder X-Ray Diffractometry (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscopy (SEM). The results of hot stage microscopic and solid-liquid phase diagram indicated formation of ketoprofen-malonic acid cocrystal. PXRD and DSC measurements showed stoichiometric ratio of cocrystal ketoprofen-malonic acid (2:1). The ketoprofen-malonic acid cocrystal had melting point at 86.2 °C and unique peaks of PXRD pattern at 2θ of 6.1°, 17.8°, 23.2° and 28.6°. FTIR spectra indicated the formation of cocrystal due to interaction of C=O ketone group of ketoprofen with MA molecule. SEM images show that ketoprofen-malonic acid cocrystal have multi-shaped particles with rough surfaces.

Enhancement of solubility and dissolution rate of atorvastatin calcium by co-crystallization

Preparation and characterization of a novel cocrystal of atorvastatin calcium with succinic acid coformer were successfully performed. This research aims to modify the crystalline form of atorvastatin calcium through cocrystallization with succinic acid coformer. The cocrystal was prepared by a solvent evaporation method and characterized by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The atorvastatin calcium-succinic acid cocrystal has new crystalline peaks at 2θ of 12.9, 18.2 and 26.7° indicating the formation of a new crystalline phase. The cocrystal showed the melting point at 205.7 °C with an enthalpy of fusion 30.2 J/g which is different from the initial components. The FTIR spectra of cocrystal showed the shifting of absorption peaks of groups of initial components indicating of formation of atorvastatin calcium-succinic acid cocrystal through acid–amide intermolecular hydrogen bond interactions. The solubility and dissolution test showed that the cocrystal has solubility and dissolution rate significantly higher than the solubility and dissolution rate of pure atorvastatin calcium.

Atorvastatin calcium (AC) is a statin drug used to lower cholesterol. Its crystalline form is usually found in the market with low solubility properties. The amorphization of crystalline AC is a technique used to increase its solubility however; the amorphous form has less thermodynamic stability. Therefore, to increase the solubility properties of its crystalline form, an AC coamorphous solid was prepared. This coamorphous solid was prepared using spray drying techniques, and coformers such as isonicotinamide (INA) and maleic acid (MA). Furthermore, characterization was carried out using powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy, and scanning electron microscopy, while the solubility properties test was conducted using the shake-flask and paddle method. The results showed that the spray-dried solids were coamorphous with single-phase homogeneous systems. Furthermore, the coamorphous solids, AC-INA and AC-MA were found to have a higher Tg than the melting points of other components, and formed intermolecular interactions between them. The higher Tg and presence of intermolecular interactions indicate that coamorphous solids are more stable than the amorphous form. Therefore, the results of the solubility and dissolution test showed that the coamorphous solid of AC-INA and AC-MA have better solubility properties compared to the AC crystalline form.

Curcumin (CUR) is a polyphenolic compound that exhibits potent anti-inflammatory activity. However, only a tiny amount of CUR is absorbed during oral administration, which is because CUR is difficult to dissolve in water. The aim of the research was to increase the solubility of CUR through the cocrystallization technique using isonicotinamide coformer (INIC) by solvent evaporation. Cocrystal characterization was carried out using a powder X-ray diffractometer (PXRD), a differential scanning calorimeter (DSC), a Fourier transform infrared spectrometer (FTIR), and a scanning electron microscope (SEM). Solubility was evaluated using the shaking method, while the anti-inflammatory activity test was carried out using the carrageenan induced mouse leg edema method. The resulting CUR-INIC (1:1) cocrystal has a diffractogram with new diffraction peaks of 2theta at 15.00, 16.22, and 22.89◦ compared to the individual diffractograms of CUR and INIC. In the cocrystal, CUR and INIC form intermolecular interactions of hydrogen bonds, resulting in a new solid phase with a melting point of 160.1◦C. The solubility of the CUR-INIC cocrystal in water was 73.1±0.23 ug/mL, which increased 14 times compared to the solubility of initial CUR, which was only 5.05±0.07 ug/mL. The CUR-INIC cocrystal showed a percentage of edema inhibition in mice (5 hours) 130% more potent than that of initial CUR. Therefore, CUR-INIC cocrystals can be used to improve CUR solubility to obtain more excellent anti-inflammatory effects.