Clozapine (CLO) is an effective atypical antipsychotic to control the symptoms of psychosis and schizophrenia. Clozapine has low solubility and high permeability, so it is classified as a class II in the biopharmaceutical classification system. The aim of this study was to improve the solubility and dissolution rate of clozapine by clozapine-isonicotinamide (CLO-INA) co-crystal formation. CLO-INA co-crystal was prepared by solvent-drop grinding (SDG) method using water as a solvent. Characterization of SDG result was conducted by powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR).  Solubility test was performed in water at room temperature. The dissolution test was performed in 900 mL of pH 6.8 phosphate buffer solution, 50 rotation per minute of paddle rotation, and at 37±0.5 °C. The PXRD pattern of  SDG result of CLO-INA has many different peaks from its parent components, and this may indicate the co-crystal formation. The solubility of the co-crystal clozapine was fifteen folds higher than pure clozapine. The dissolution rate of CLO-INA co-crystal increased in the first 10 minutes compared to pure clozapine. Percentage of clozapine dissolved after 10 minutes from CLO-INA co-crystal and pure CLO were 10.2 and 2.4%, respectively. CLO and INA can form co-crystal by SDG method that can improve the solubility and dissolution rate of clozapine.Keywords: Clozapine, Isonicotinamide, Co-crystal, Solubility, Dissolution

The formation of co-amorphous is one alternative that can be attempted to enhance the solubility of drugs. The study aimed to identify the co-amorphous formation between candesartan cilexetil (CAN) and l-arginine (ARG) and to know its effect on the solubility and dissolution rate of candesartan cilexetil. Initial prediction of co-crystal formation was undertaken by observing differences in crystal morphology between the candesartan cilexetil-l-arginine (CAN-ARG) mixture and each of its initial components due to crystallization in ethanol. The CAN-ARG co-amorphous was produced by the liquid-assisted grinding (LAG) method with the same molar ratio of the CAN and ARG mixture using ethanol as solvent. The co-amorphous formation of CAN-ARG was identified by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) methods. The solubility and dissolution test was performed to know the impact of the co-amorphous CAN-ARG formation. The PXRD pattern of CAN-ARG of LAG result showed a very low peak intensity compared to pure CAN and ARG. The DSC thermogram of the CAN-ARG LAG result does not show any sharp endothermic peaks. The PXRD and DSC results reveal that CAN and ARG can form co-amorphous. The solubility and dissolution rate of candesartan cilexetil in co-amorphous CAN-ARG was better than that of pure CAN. It can be concluded, liquid-assisted grinding of CAN-ARG mixture is identified to form co-amorphous which has an impact on increasing the solubility and dissolution rate of candesartan cilexetil.

An effort to improve the solubility of albendazole (ABZ), an anthelmintic drug has been successfully carried out through the formation of multicomponent crystal with dl-malic acid (MAL). Construction of phase solubility curve of ABZ in MAL solution and crystal morphological observations after recrystallization in the acetone-ethanol (9:1) mixture were performed for initial prediction of multicomponent crystal formation. ABZ-MAL multicomponent crystal was prepared by wet grinding or also known as solvent-drop grinding (SDG) with acetone-ethanol (9:1) mixture as a solvent followed by characterization of the multicomponent crystal formation by powder X-ray diffraction and Fourier transform infrared (FTIR) methods. The solubility of ABZ-MAL multicomponent crystal was tested in water at ambient temperature and in pH 1.2, 4.5 and 6.8 of buffered solutions at 37°C. The phase solubility curve of the ABZ in the MAL solution showed type Bs. The ABZ-MAL mixture has a different crystalline morphology than pure ABZ and MAL after recrystallization in the acetone-ethanol mixture (9:1). The powder X-ray diffraction pattern and the FTIR spectrum of ABZ-MAL from SDG different from intact ABZ and MAL powder X-ray diffraction patterns and these results can indicate the ABZ-MAL multicomponent crystal formation. The ABZ-MAL multicomponent crystal has better solubility than pure ABZ in all media used. These results can be concluded that ABZ-MAL multicomponent crystal can be prepared by solvent-drop grinding method with acetone-ethanol (9:1) mixture as a solvent and can increase the solubility of albendazole.

Objective: Loratadine (LOR) is a biopharmaceutics classification system Class II drug that has low solubility and high permeability, so its absorption rate is determined by the dissolution rate. The aim of this study was to prepare an LOR-fumaric acid (LOR-FUM) binary mixture and to investigate its influence on the solubility and dissolution rate of LOR.Methods: LOR-FUM binary mixture was prepared by the wet grinding method in an equimolar ratio by the addition of two drops of methanol. Characterization of LOR-FUM binary mixture was conducted by the construction of the phase solubility, powder X-ray diffractometry, Fourier transforms infrared spectroscopy, and polarizing microscopy methods. Solubility test was performed in water at room temperature, whereas the in vitro dissolution test was performed in the pH 1.2, 4.5, and 6.8 buffer solutions. Results:The phase solubility curve of LOR in FUM solution is similar to type B S . The powder X-ray diffraction results show the crystallinity of LOR was changed become more amorphous indicating the salt formation. Fourier transforms infrared spectroscopy (FTIR) spectra of LOR-FUM binary mixture showed the vibration peaks of an imine group on the pyridine ring of LOR and carbonyl group on the FUM are not detected. On the other hand, the polarizing microscope images showed the crystal habit of LOR-FUM binary mixture after recrystallized from methanol contrast to crystal habit of its pure components. The solubility in water of LOR-FUM binary mixture was higher than pure LOR. Amount of LOR released from LOR-FUM binary mixture in pH 4.5 and 6.8 buffer solutions was faster than from pure LOR. Conclusion:A binary mixture of LOR and FUM may improve the solubility and dissolution rate of LOR.

<p align="center"><strong>Abstrak</strong></p><p><em> </em></p><p>Kalium diklofenak adalah salah satu obat golongan anti-inflamasi non steroid (AINS) yang memberikan efek samping iritasi pada saluran pencernaan. Tujuan penelitian ini adalah melakukan formulasi dan evaluasi sediaan dengan rute alternatif lain penggunaan kalium diklofenak melalui transdermal <em>patch. Patch </em>dibuat dengan metode penguapan pelarut. Polivinil pirolidon (PVP) digunakan sebagai polimer untuk pembentukan <em>patch </em>transdermal kalium diklofenak dengan dibutil ftalat (DBP) sebagai <em>plasticizer </em>dan mentol sebagai peningkat penetrasi. Uji <em>in vitro</em> dilakukan dengan alat difusi modifikasi <em>Franz </em>dan ditentukan dengan spektroskopi UV-sinar tampak. Kadar zat aktif, berat, ketebalan dan organoleptis dari <em>patch </em>juga ditentukan. Hasil penelitian menunjukan bahwa rata-rata uji laju difusi sediaan <em>patch </em>1,3884 mg/cm² dengan persen permeasi sebesar 8,9 % selama 180 menit.</p><p>           </p><p><strong>Kata Kunci :</strong><strong> </strong>Transdermal; <em>Patch</em>; kalium diklofenak; mentol.<strong></strong></p><p><em> </em></p><p align="center"><strong><em>Formulation and Evaluation Patch Transdermal Diclofenac Potassium</em></strong></p><p align="center"><em> </em></p><p align="center"><strong><em>Abstract</em></strong></p><p><em> </em></p><p><em>Diclofenac potassium is one of the non-steroidal anti-inflammatory drugs (NSAIDs) that provides irritating side effects to the digestive tract. The purpose of this study is to formulate and evaluate preparations with alternative routes of using potassium diclofenac through the transdermal patch. </em><em>Preparation of </em><em>the matrix patches used the solvent casting method. Polyvinyl pyrrolidone (PVP) was used as a matrix for the formation of transdermal diclofenac potassium patches, dibutyl phthalate (DBP) as the plasticizer and menthol as the permeation enhancer. The in vitro assay was carried out in a modified Franz diffusion cell and the rates of diffusion were determined by UV spectroscopy. The average drug content, thickness, organoleptic, weight uniformity of the matrix patches was also determined. The results showed that the average dosage rate of diffusion test Patch </em><em>is </em><em>1,3884 mg/cm² with permeation percentage 8,9 % for 180 minutes. </em></p><p><em> </em></p><p><strong><em>Keywords</em></strong><em>: </em><em>Transdermal; Patch; diclofenac potassium; menthol</em></p>