SOLUBILITY ENHANCEMENT OF KETOCONAZOLE VIA SALT AND COCRYSTAL FORMATION

Objective: Pharmaceutical salt and cocrystal is a promising alternative method for improving the solubility and dissolution rate of active pharmaceutical ingredients. In this work, an attempt was made to improve solubility of ketoconazole (KTZ) using salt formation and cocrystallization technique.Methods: Salt and cocrystal were prepared using oxalic acid (OXA) and fumaric acid (FUMA) via slurry conversion method. Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscope (SEM) techniques were employed to investigate the crystallinity, melting point and morphology of salt and cocrystal respectively. KTZ salt and cocrystal were evaluated further for their solubility, stability and antifungal activities.Results: Synthesis of KTZ OXA salt and KTZ FUMA cocrystal were successfully carried out using slurry conversion method using ethyl acetate solvent. The result from PXRD, DSC and SEM analysis confirms the formation of salt and cocrystal of KTZ with OXA and FUMA. Saturation solubility studies in water at 25 °C exhibited a remarkable improvement in the drug solubility. KTZ FUMA and KTZ OXA were considered to be stable over the period of 1 month confirmed by the stability study. In vitro antifungal activity study revealed that the formation of KTZ OXA and KTZ FUMA did not alter the therapeutic activity as an antifungal agent.Conclusion: Salt and cocrystal of KTZ (KTZ OXA and KTZ FUMA) exhibit enhanced solubility compare the pure drug. In vitro antifungal study revealed that both salt and cocrystal of KTZ retained their antifungal activities

VIABILITAS PROBIOTIK Lactobacillus acidophilus DLBSD102 SETELAH MIKROENKAPSULASI

Viability of Lactobacillus acidophilus DLBSD102 after Microencapsulation      This study was aim to select the viability the Lactobacillus acidophilus DLBSD102 during the spray drying method, to produce a fermented milk powder containing probiotic. Since spray drying process use the high temperature, suitable encapsulation material will increase the vaibility of probiotic and the quality of the final product. Three different encapsulation materials which were maltodextrin, whey protein isolate, and inulin with several formulations were used. The spray drying temperature used in this study was 130°C (inlet) and 60°C (outlet). The quality of the fermented milk powder containing L.acidophilus DLBSD102 bacteria strain was evaluated by measure the bacterial viability, bacterial cell resistance from hot temperatures, bile salts (0.5%) low pH (pH 2.0), and the presence of possible pathogenic bacteria. The results showed that the additional encapsulation material of inulin yielded a good quality fermented milk powder, compared with a mixture of encapsulation materials of maltodextrin: whey protein isolate (3:1), based on viability of probiotics after spray drying was increased, bacterial cell resistance to hot temperature, bile salt (0.5%) low pH (pH 2.0), and resistance to the presence of pathogenic bacteria. The addition of encapsulation material in the form of inulin yielded viability of BAL bacteria with log decrease of 0.20 ± 0,01 log CFU/g whereas without inulin addition decreased by 0.51± 0.36 log CFU/g when dried. Therefore, the mixture of encapsulation materials :maltodextrin:whey protein isolate:inulin (3:1:1) is used in the microencapsulation process of BAL by yielding 8.93% heat resistance, bile salt resistance of 78.55%, resistance to pH 2 of 77.25%, total titrated acids by 2.38%, moisture content during storage of 4.33% (4°C) and 3.96% (25°), pH value during fermentation process was 3.59±0,35 and no pathogenic bacteria was detected during production, packaging and storage for 4 weeks.Keywords: L. acidophilus DLBSD102, microenkapsulation, enkapsulation material, spray dryingABSTRAK      Penelitian ini tentang viabilitas Lactobacillus acidophilus DLBSD102 menggunakan bahan enkapsulan yang sesuai dengan metode pengeringan semprot. Tujuannya menghasilkan sediaan produk probiotik berupa serbuk susu fermentasi. Efektivitas mikroenkapsulasi dapat ditingkatkan dengan pemilihan jenis bahan enkapsulan yang tepat saat akan dikeringkan. Suhu pengeringan semprot yang digunakan dalam penelitian ini adalah 130°C (inlet) dan 60°C (outlet). Bahan enkapsulan yang digunakan adalah campuran dari maltodekstrin:whey protein isolate:inulin (3:1:1). Kualitas serbuk susu fermentasi dari strain bakteri L.acidophilus DLBSD102 yang diperoleh dievalusi termasuk viabilitas bakteri, ketahanan sel bakteri terhadap suhu panas, garam empedu (0,5%) pH rendah (pH 2,0) dengan metode cawan tuang, dan evaluasi kemungkinan adanya bakteri patogen. Hasil penelitian menunjukkan bahwa bahan enkapsulan tambahan berupa inulin menghasilkan serbuk susu fermentasi dengan kualitas yang baik, dibandingkan dengan campuran bahan enkapsulan berupa maltodekstrin:whey protein isolate (3:1), yang didasarkan pada viabilitas probiotik setelah pengeringan semprot dan meningkatkan, ketahanan sel bakteri terhadap suhu panas, garam empedu (0,5%) pH rendah (pH 2,0), dan ketahanan terhadap adanya bakteri patogen. Penambahan bahan enkapsulan berupa inulin menghasilkan viabilitas bakteri BAL dengan log penurunan sebesar 0,20±0,01 log CFU/g sedangkan tanpa penambahan inulin mengalami penurunan sebesar 0,51±0,36 log CFU/g saat dikeringkan. Oleh sebab itu, campuran bahan enkapsulan maltodekstrin:whey protein isolate:inulin (3:1:1) digunakan dalam proses mikroenkapsulasi BAL dengan menghasilkan ketahanan terhadap panas sebesar 8,93%, ketahanan terhadap garam empedu sebesar 78,55%, ketahanan terhadap pH 2 sebesar 77,25%, total asam tertirasi sebesar 2,38%, kadar air selama penyimpanan sebesar 4,33% (4°C) dan 3,96% (25°), nilai pH selama proses fermentasi sebesar 3,59±0,35 dan serbuk susu fermentasi tidak mengandung bakteri patogen selama proses produksi, pengemasan hingga penyimpanan selama 4 minggu.Kata kunci: Probiotik L. acidophilus DLBSD102, mikroenkapsulasi, bahan enkapsula