Solid-state nuclear magnetic resonance (NMR) spectra of pharmaceutical dosage forms.

Solid-state 13C NMR spectra of tablets or capsules of prednisolone, enalapril maleate, lovastatin, simvastatin, ibuprofen, flurbiprofen, mefenamic acid, indomethacin, diflunisal, sulindac, and piroxicam were obtained in the CP/MAS mode at 50 MHz. These studies show that (1) solid-state NMR spectroscopy can detect the active ingredients in low-dose tablets and capsules; (2) the use of interrupted decoupling often results in suppression of resonances due to excipients, thereby allowing better detection of resonances from the drug; and (3) the technique permits discrimination between two prednisolone polymorphs present in tablets obtained from various manufacturers even though the tablets contain only approximately 5% (w/w) of the drug.

Novel process for the production of cellulolytic enzymes.

A novel process for the production of extracellular carboxymethylcellulase (CMCase) and xylanase by fermentation under nonaseptic or nonsterile conditions is described. The fermentation process is carried out under very acidic conditions of pH 2.0 by using a acidophilic cellulolytic fungus. Microbial contamination is avoided or minimized to an insignificant level under this acid pH condition. The culture medium for this production consists of a carbon source from cellulosics or lignocellulosics, such as Na-CMC, xylan, Avicel cellulose, cellulose powder, alpha-cellulose, sawdust, etc., or a mixture of the forementioned together with simple ingredients such as (NH(4))(2)SO(4), K(2)HPO(4), MgSO(4) and NaNO(3). The fermentation is carried out at room temperature (28-30 degrees C), under aerobic conditions, and without controlling the pH. The CMCase and xylanase produced are stable under very simple storage conditions, such as in the fresh culture medium not containing the substrate for a period of 3 days, at any temperature from 0 to 30 degrees C. These extracellular enzymes have an optimum pH around 3, with the best range of pH from 2.0 to 3.6, for any temperature between 15 and 60 degrees C. The optimum temperatures are 55 degrees C for CMCase activity and 25-50 degrees C for xylanase activity, at any pH between 2.0 and 5.2. The apparent Michaelis constants Km are 2.6 and 1.5 mg/mL for CMCase and xylanase of the culture filtrate, respectively.

Effect of dilution on carboxymethylcellulase and xylanase assays.

It has been demonstrated that the dilution of samples prior to the carboxymethylcellulase and xylanase assays causes serious discrepancies in the numerical values obtained for the enzyme activities. Even when the sample is assayed with the identical procedure, one could obtain different numerical values of the enzyme activity U depending on how much this sample has been diluted before the enzyme assay. Two crude commercial cellulase samples of Aspergillus niger and Trichoderma viride as well as the culture filtrate of our newly isolated acidophilic fungus have been used for the demonstration. An empirical method for reporting the cellulolytic activity by taking into account this dilution effect is proposed.