Pharma-UP Magazine (May 2018) : Dr. Nyi Mekar Septarini, M.Si., Apt. and Dr. Iyan Sopyan, M.Si., Apt.

Cartilage oligomeric matrix protein (COMP) is a potential biomarker to monitor the development of cartilage damage and injury in rheumatoid arthritis (RA). The most accurate method of determining COMP levels is the enzyme-linked immunosorbent assay, but this method is expensive and requires trained analysts. An alternative method to solve this problem is analyzing the electropherogram profile of crude COMP. This method separates proteins based on molecular weight, so it can differentiate pentamer COMP from its fragments. This study was conducted to analyze the electroferogram profile of crude COMP of RA patients and normal individuals, so it can be applied to RA diagnosis. COMP was precipitated on its isoelectric pH, then crude COMP was dissolved and electrophoresed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE).The electropherogram profiles of RA patients were dominated by pentamer and dimerbands, whereas the electropherogram profiles of normal individual were dominated by tetramer, trimer, and dimer bands. Increased pentamer COMP in serum was indicated by the cartilage damage. The electropherogram profile of crude COMP of RA patient can be differentiated from normal individuals, so it can be used for the RA diagnosis.

Key words: Serum, Crude COMP, Precipitation, Isoelectricp H, SDS-PAGE.

Objective : The aim of this study was to explore co-crystallization to enhance the solubility of simvastatin (SV) as a drug of choice for hypercholesterolemia using saccharin (Sacch) as co-former. Methods: Molecular modeling of sacch against SV has been conducted by in silico using auto dock 4.2. Preparation of co-crystal has carried out by solvent evaporation (SE) using an equimolar ratio of SV and Sacch. Co-crystal of SV- Sacch was evaluated by the saturated solubility test and intrinsic dissolution test. Afterward, the co-crystal was characterized by infrared spectrophotometry (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), binary phase diagram and stability studies in storage condition 400C and relative humidity (RH) 75% for three months. Results: In silico studies showed that the interaction of SV against sacch has hydrogen bonding as molecular synthon. Evaluations of solubility and intrinsic dissolution have shown an increased in rate properties significantly of co-crystal as compared to pure SV and its physical mixer (PM). Characterizations of a co-crystal SV: sacch (1: 1) has indicated the formation of different new solid crystal phase as compared to SV, sacch, and its PM, and stable for

400C and RH 75% in 3 months. Conclusion: Co-crystallization has been used to increase the solubility and dissolution rate of simvastatin and all characterization has shown the formation of co-crystal SV: sacch (1: 1).

Key words: Co-crystal, Simvastatin, Saccharin, Solubility, Dissolution.