Purpose: To obtain quercetin-isonicotinamide co-crystal (CQINA) with improved physicochemical and in-vitro dissolution characteristics. Methods: Co-crystallization of quercetin (Q) and isonicotinamide (INA) in molar ratio of 1:1 was performed using solvent evaporation method with the addition of 50 mL of ethanol (99.9%, v/v). The resultant solution was thoroughly mixed and stirred at room temperature for 48 h to slowly evaporate the solvent until CQINA was obtained. The co-crystal phase was characterized using differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), scanning electron microscopy (SEM), and fourier transform infrared (FTIR) spectroscopy. In-vitro dissolution was performed by USP method II in 900 mL citrate buffer (pH 5.0 ± 0.05), with stirring at 100 rpm and at 37 ± 0.5 °C. Results: Computational approach predicted the formation of hydrogen bonds between Q and coformers used, and the interaction involved minimum energy. In CQINA thermogram, a new endothermic peak was formed with a melting point of 255.26 °C, while Q (314.85 °C) and INA (156.62 °C). Images from DSC, PXRD, SEM and FTIR showed that the crystal habits and morphologies of the CQINA differed from those of the original components. There was an improvement in the dissolution profile of CQINA, when compared with those of the original components. Conclusion: Q and INA subjected to solvent evaporation result in the formation of a CQINA with different crystal habit, which possess physicochemical characteristics different from those of its constituents. Modification of Q crystals in CQINA increases its in vitro dissolution, making it a potential pharmaceutical agent.

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.

The purpose of this study was to investigate the effect of andrographolide-carboxymethyl chitosan nanoparticles formation on the physical characteristics, in vitro release profile and in vivo antimalarial activity of andrographolide. Nanoparticles were prepared by ionic gelation method-spray drying using CaCl₂ as the crosslinker with a composition of drug: polymer: CaCl₂=40: 250: 100. The obtained particles were evaluated for its size and morphology; physical state, drug content, in vitro drug release and in vivo antimalarial activity on Plasmodium berghei infected mice. The results of DTA and XRD showed that nanoparticle systems had a lower melting point and lower crystallinity degree. The drug dissolved from the nanoparticles was increased up to 6.5 times and the in vivo antimalarial activity was 1.65 times higher compared to andrographolide. The formation andrographolide-carboxymethyl chitosan nanoparticles affected the physical characte-ristics of andrographolide. The decrease crystallinity of andrographolide resulted in a lower melting point of andrographolide. Such changes provided a positive impact to the drug dissolution and then its activity.

Physical Characteristics of Liposomal Formulation Dispersed in HPMC Matrix and Freeze-Dried Using Maltodextrin and Mannitol as Lyoprotectant

Quercetin is one of the flavonoids with a polyhydroxyaromatic structure. Quercetin has been proposed to exhibit a bioWactivity against oxidative stress. However, quercetin has poor solubility in aqueous media. The purpose of this study was to investigate the physicochemical properties and dissolution rates of quercetin-succinic acid co-crystals. The quercetin-succinic acid co-crystals were prepared in 1:1 molar ratio using solvent evaporation. X-ray diffraction, differential thermal analysis, infrared spectroscopy, and scanning electron microscopy were performed to determine the physicochemical properties of quercetin-succinic acid co-crystals. Dissolution was studied in medium citrate buffer with 2% SLS for 60 min using USP II (paddle) apparatus at 100 rpm and 37°C. Based on diffractogram, thermogram, infrared spectrum, and microscopic capture, the physicochemical properties of quercetin-succinic acid co-crystals showed difference to those of quercetin. In addition, the in vitro dissolution test showed that the dissolution profile of co-crystals was significantly higher than pure quercetin. This study suggests that the formation of quercetin-succinic acid co-crystals using solvent evaporation enhanced the physicochemical properties and dissolution rate of quercetin.

Purpose: To determine the physicochemical properties and in vitro dissolution profile of quercetinmalonic acid co-crystals prepared using solvent-drop grinding method. Methods: Co-crystallization of quercetin (Q) and malonic acid (MA) in molar ratios of 1:1 (CC1) and 1:2 (CC2) was performed by solvent-drop grinding method with addition of 20 % (w/v) ethanol in a shaker mill run for 30 min. The co-crystal phase was characterized by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), scanning electron microscopy (SEM), and fourier transform infrared (FT-IR) spectroscopy. In vitro dissolution was performed using the paddle method at 100 rpm in the medium of citrate buffer (pH 5.0 ± 0.05) containing 2.0 % (w/v) sodium lauryl sulfate at 37 ± 0.5 °C. Results: Thermograms from DSC showed that CC1 and CC2 co-crystals had endothermic peaks at 283.02 and 266.61 °C, respectively. These peaks were in-between the melting points of Ma and Q. The powder diffractogram of CC1 showed new diffraction peaks at 16.21, 19.87, and 28.88 °, while CC2 showed new ones at 16.18, 19.86, and 28.83 °. There were OH- band shifts in IR spectra from 3411 to 3427 cm^-1 for CC1, and from 3411 to 3466 cm^-1 for CC2. Images from SEM indicate that the crystal habits and morphologies of the co-crystals differed from those of the original components. The dissolution efficiency of CC2 increased 1.056 times relative to pure Q. Conclusion: Co-crystal phase of Q and MA prepared using solvent-drop grinding (CC1 and CC2) displays physicochemical characteristics different from those of the physical mixtures and their pure components. There is an increase in vitro dissolution as a result of co-crystal formation. Keywords: Co-crystal, Dissolution, Malonic acid, Quercetin, Solvent-drop grinding