Response surface methodology for optimization of production of lovastatin by solid state fermentation

Lovastatin, an inhibitor of HMG-CoA reductase, was produced by solid state fermentation (SSF) using a strain of Aspergillus terreus UV 1718. Different solid substrates and various combinations thereof were evaluated for lovastatin production. Wheat bran supported the maximum production (1458 ± 46 µg g-1 DFM) of lovastatin. Response surface methodology (RSM) was applied to optimize the medium constituents. A 2(4) full-factorial central composite design (CCD) was chosen to explain the combined effects of the four medium constituents, viz. moisture content, particle size of the substrate, di-potassium hydrogen phosphate and trace ion solution concentration. Maximum lovastatin production of 2969 µg g-1 DFM was predicted by the quadratic model which was verified experimentally to be 3004 ± 25 µg g-1 DFM. Further RSM optimized medium supplemented with mycological, peptone supported highest yield of 3723.4±49 µg g-1 DFM. Yield of lovastatin increased 2.6 fold as with compared to un-optimized media.

Spectrofluorometric determination of the two antilipemic drugs lovastatin and simvastatin in spiked human plasma and in dosage forms

A new spectrofluorimetric method for the determination of the two antilipemic drugs, lovastatin and simvastatin, was described. The method is based on heating drug solution with 2-aminoethane sulfonic acid [taurine] 0.025% w/v solution in phosphate-borate buffer of pH 7.4 at 70C for 30 minutes. The resulting reaction product exhibits strong fluorescence at 388 nm after excitation at 318 nm. Different assay parameters have been optimized to achieve maximum sensitivity and reliability of the method for the determination of the 2 drugs in spiked human plasma as well as in their dosage forms. The intensity of the resulting fluorescence showed linear relation with concentrations of both drugs in the range of 0.2 to 0.8 mug/L. The mean percentage recoveries of lovastatin and simvastatin were 99.851 SD +/- 2.101 and 99.806 SD +/- 1.805, respectively, in case of six concentrations of human plasma. The limit of detection was found to be 0.2 mug/L. The method is recommended for drug monitoring in biological fluids. The method was successfully applied for the determination of lovastatin and simvastatin in dosage forms. The results were in agreement with those of some other reported methods