Pembentukan ko-amorf irbesartan-l-arginin dan dampaknya terhadap kelarutan dan laju disolusi irbesartan

Abstrak Latar Belakang: Irbesartan (IBS) adalah antihipertensi yang bekerja menghambat sistem renin-angiotensin dan memiliki kelarutan rendah dalam air, sehingga bioavailabilitasnya terbatas. Tujuan penelitian ini adalah untuk menghasilkan ko-amorf irbesartan dengan l-arginin (ARG) dan untuk mengetahui dampaknya terhadap kelarutan dan laju disolusi irbesartan. Metode: Pembuatan kurva kelarutan fasa dilakukan dengan menentukan kelarutan IBS di dalam rentang konsentrasi 0,1-1,1M dari larutan ARG di dalam air. Ko-amorf dibuat dengan menggiling 1,716 g IBS, 0,696 g ARG, dan lima tetes metanol di dalam Retsch mortar grinder RM 200 selama 15 menit. Untuk mengetahui terbentuknya ko-amorf dilakukan karakterisasi menggunakan difraktometer sinar-X serbuk dan differential scanning calorimeter (DSC). Uji kelarutan dalam media air dilakukan di suhu ruang, sedangkan dalam media larutan dapar pH 1,2 dan 6,8 dilakukan di suhu 37±°C. Larutan dapar pH 1,2 dan 6,8 juga digunakan sebagai media pengujian laju disolusi. Hasil: Kurva kelarutan fasa IBS di dalam larutan ARG menunjukkan tipe AL. Difraktogram menunjukkan terbentuknya ko-amorf IBS-ARG setelah penggilingan. Termogram DSC hasil penggilingan juga menunjukkan telah terbentuk ko-amorf setelah penggilingan basah dengan transisi gelas (Tg) pada 82,2°C. Kelarutan ko-amorf IBS-ARG di dalam air, larutan dapar pH1,2 dan 6,8 berturut-turut 7,2, 2,0, dan 1,9 kali lebih tinggi daripada IBS murni. Laju disolusi ko-amorf IBS-ARG pada kedua media lebih cepat daripada IBS murni. Kesimpulan: Ko-amorf IBS-ARG telah sukses dibuat dengan metode penggilingan basah yang menyebabkan kelarutan dan laju disolusinya lebih baik daripada IBS murni. Abstract Background: Irbesartan (IBS) is an antihypertensive is an antihypertensive which acts to inhibit the renin-angiotensin system and has low water solubility, thus its bioavailability is limited. The aim of this study was to produce co-amorphous irbesartan-l-arginine (IBS-ARG) and to determine its impact on solubility and dissolution rate of irbesartan. Method: Preparation of phase solubility curve was carried out by determining the solubility of IBS in the concentration range 0.1-1.1 M of the ARG solution in water. Co-amorphous was prepared by grinding of 1.716 g IBS, 0.696 g ARG, and five drops of methanol in a Retsch mortar grinder RM 200 for 15 minutes. To determine the formation of co-amorphous, characterization was conduct by a powder X-ray diffractometer and a differential scanning calorimeter (DSC). The solubility test in aqueous medium was carried out at room temperature, while in the buffer solution media pH 1.2 and 6.8 was carried out at 37±0.5°C. The buffer solutions of pH 1.2 and 6.8 were also used as media for dissolution rate testing. Results: The IBS phase solubility curve in the ARG solution showed the AL type. The diffractogram showed the formation of IBS-ARG co-amorphous after wet milling. The DSC thermogram also showed that it was co-amorphous after grinding with a glass transition (Tg) at 82.2°C. The solubility of co-amorphous IBS-ARG in water, pH1.2 and 6.8 of buffer solutions were 7.2, 2.0, and 1.9 folds higher than pure IBS, respectively. The dissolution rate of IBS-ARG co-amorphous in both test media was faster than pure IBS. Conclusion: The IBS-ARG co-amorphous has been successfully prepared by the wet milling method which causes better the solubility and dissolution rate than pure IBS.

Perbaikan Kelarutan Albendazol Melalui Pembentukan Kristal Multikomponen dengan Asam Malat

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.