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ABSTRACT

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.

Kayu secang (Caesalpinia sappan L.) dilaporkan memiliki sifat antioksidan alami. Brazillin merupakan salah satu kandungan senyawanya yang berkhasiat sebagai antioksidan. Antioksidan dapat digunakan untuk mencegah penuaan dini pada kulit. Essence adalah salah satu kosmetik yang mengandung antioksidan topikal. Essence memiliki keunggulan dibandingkan produk perawatan kulit lainnya dan essence lebih mudah menyerap ke dalam kulit. Tujuan penelitian ini adalah untuk mengoptimalkan dan mengevaluasi essence ekstrak etanol kayu secang sebagai antioksidan topikal. Simplex lattice design digunakan untuk mengevaluasi pengaruh konsentrasi butilen glikol dan gliserin pada karakteristik essence. Metode yang digunakan dalam ekstraksi adalah maserasi dengan pelarut etanol. Hasil penelitian menunjukkan bahwa butilen glikol dan gliserin dapat meningkatkan viskositas dan nilai pH essence. Formula essence optimum terdiri dari 10% butilen glikol dengan prediksi nilai viskositas 2,944 dPas dan pH 5,075. Formula optimum essence ekstrak kayu secang memiliki tekstur kental, bau khas ekstrak, berwarna kuning kecoklatan, homogen, dan memiliki daya sebar 14 cm.

This study aimed to improve the solubility of quercetin by solvent pH control method and crystal modification through co-crystal formation using isonicotinamide as its co-former. Solubility of quercetin was tested at nine pH levels using phosphate buffer solvents. Quercetin-isonicotinamide co-crystal was prepared by a solvent evaporation method. Co-crystal preparation was carried out using two different stoichiometric ratios of quercetin-isonicotinamide (1:1 and 1:3). The co-crystalline solubility test was performed in 50 mL citrate buffer (pH 5.0 ± 0.05) at a temperature of 37 ± 0.5C. The thermodynamic parameters of quercetin and co-crystal were analyzed to determine the mechanism of the quercetin solubility process. Increasing the pH of solvents has proven to increase the solubility of quercetin. The quercetin oxidation reaction starts at pH level of 7.4. The formation of quercetin-isonicotinamide co-crystal at ratio of 1:1 and 1:3 shows the increase of quercetin solubility by 1.36 and 1.27 times, respectively. The thermodynamic parameters of the quercetin and quercetinco-crystal, which include entropy, enthalpy, and free energy values, can be used to explain the solubility process of quercetin. Quercetin has increased solubility under alkaline pH conditions, but undergoes an oxidation reaction at pH 7.4 and easily oxidized at alkaline pH. Crystal modification of quercetin by the co-crystal formation method has proven to increase the solubility of quercetin so that it can be used for the development of quercetin as a candidate for effective, safe, and acceptable active pharmaceutical ingredient.