Kajian Sistem Dispersi Padat Tenoksikam-Hidroksi Propil Metil Selulosa dan Efektifitas Analgesiknya

Tenoksikam merupakan obat analgetik dan anti inflamasi NSAID, golongan oksikam. Tenoksikam termasuk dalam obat BCS kelas II dengan kelarutan 14,1mg/L. Tujuan dari penelitian adalah untuk mempersiapkan sistem dispersi padat tenoksikam dengan HPMC dan meningkatkan kelarutan, laju disolusi dan aktivitas analgesik in vivo. Penelitian dilakukan dengan membuat dispersi padat Tenoksikam dengan HPMC dengan teknik freezdrying dalam tiga perbandingan obat terhadap pembawa (1:1, 1:2 dan 2:1 b/b). Serbuk dispersi padat dikarakterisasi sifat-sifat keadaan padatnya meliputi; Difraksi sinar-X, kalorimetri pemindaian diferensial, spektroskopi FT-IR dan mikrokopis SEM. Evaluasi yang dilakukan adalah uji perolehan kembali, uji kelarutan, uji disolusi dan uji Aktivitas analgetik dengan metode Writhing test. Hasil analisis pola difraksi sinar-X diperoleh Persen kristalin dari Fd 1:1, Fd 1:2 dan Fd 2:1 sebesar 58,452%; 52,598% dan 70,310%. Hasil kelarutan rata rata dari Tenoksikam, Fd 1:1, Fd 1:2 dan Fd 2:1 adalah 3,147 mg/100mL, 22,043 mg/100mL, 25,170 dan 20,136 mg/100mL. Nilai Q45 dari Tenoksikam (40,326±2,319), Fd 1:1 (89,73±0,943%) Fd 1:2 (93,278±0,905%) dan Fd 2:1(71,486±2,435). Tes mengeliat terhadap mencit putih jantan diperoleh jumlah mencit menggeliat yang diberikan larutan 1% NaCMC (75,20±7,33 kali), Tenoksikam (45,80±15,60 kali) dan Fd 1:2 (20,20±7,19 kali). % inhibisi nyeri Tenoksikam (39,10 %) dan Fd 1:2 (73,14%). Adanya perbedaan signifikan nilai rata-rata uji analgetik antar kelompok Fd 1:2, Tenoksikam dan NaCMC 1% ( nilai p<0,05). Terjadinya peningkatan kelarutan Fd 1:2, Fd 1:1 dan Fd 2:1 sebanyak 8 kali, 7,1 kali dan 6,4 kali dibandingkan dengan Tenoksikam. Fd 1:2 menunjukan nilai Q45 terbaik dengan perbedaan signifikan nilai rata-rata kelarutan dan nilai Q45 antar kelompok Tenoksikam, Fd 1:1, Fd 1:2 dan Fd 2:1 ( nilai p<0,05). Terjadinya peningkatan inhibisi nyeri Fd 1:2 dibandingkan dengan Tenoksikam dengan perbedaan signifikan nilai rata-rata uji analgetik antar kelompok Fd 1:2, Tenoksikam dan NaCMC 1% (nilai p<0,05

FORMATION AND CHARACTERIZATION OF MULTICOMPONENT CRYSTAL OF TRIMETHOPRIM AND MANDELIC ACID BY SOLVENT DROP GRINDING METHOD

Objective: To increase the solubility of trimethoprim by forming multicomponent crystals using mandelic acid as a coformer. Methods: Multicomponent crystals of trimethoprim and mandelic acid were prepared at a ratio of 1:1 mol by the Solvent Drop Grinding (SDG) method. Solid state characterization was carried out using Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscope (SEM), and polarized microscope. The solubility test of trimethoprim was carried out in CO2-free distilled water using a sonicator for 5 min and then determined by High-Performance Liquid Chromatography (HPLC) using acetonitrile and phosphoric acid in a 10:90 ratio as the mobile phase and octadecylsilane (C18) as the stationary phase. Results: The results showed a decrease in the melting point and enthalpy of fusion on the DSC thermogram, a new peak in the X-ray diffraction pattern, and a slight shift of wave number in the FTIR spectroscopy. Those characterizations indicated that the multicomponent crystal formed a salt type. SEM analysis showed morphological changes and formation of new crystal habits. The polarization microscopy analysis showed birefringent with various colors in all samples. The solubility of multicomponent crystal is 2.73-times higher compared to intact trimethoprim. Conclusion: The formation of cocrystals of trimethoprim and mandelic acid by SDG method increased the solubility of trimethoprim

Kajian sistem dispensasi padat tenoksikam hidroksi propil metil selulosa dan efektiftas analgesiknya

xv ,97 hlm 21x29 c

PREPARATION OF SPRAY-DRIED MULTICOMPONENT CRYSTALS OF TRIMETHOPRIM-MANDELIC ACID AND ITS PHYSICOCHEMICAL CHARACTERIZATION

Objective: Trimethoprim is a wide-spectrum antimicrobial compound belonging to Class II of the Biopharmaceutics Classification System (BCS), with high permeability but low solubility. This study aimed to prepare a multicomponent crystal (MCC) of trimethoprim-mandelic acid to enhance the solubility of trimethoprim. Methods: MCC trimethoprim–mandelic acid was prepared by spray drying technique. Solid-state characterizations were performed by using PowX-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier-transform infrared (FT IR) spectroscopy, Scanning Electron Microscopy (SEM), and polarized microscopy. The solubility test was performed in distilled water. The amount of dissolved trimethoprim was analyzed by High-Performance Liquid Chromatography (HPLC) using acetonitrile and phosphoric acid 1 % (10:90 v/v) as the mobile phase. Results: MCC characterizations showed a different diffraction pattern from its intact materials according to PXRD analysis, a decrease in the melting point in the DSC thermogram, a shift of the wave number in the FT-IR spectra, and a new crystalline habit compared to the intact materials was presented by SEM analysis. The MCC also showed the color of interference under polarized microscopy, indicating the crystalline phase. The solubility of trimethoprim in MCC increased significantly by 3.98 times in comparison to intact trimethoprim. Conclusion: The MCC trimethoprim-mandelic acid by spray drying technique enhanced the solubility of trimethoprim