The use of near-infrared spectroscopy to monitor the mobility of water within the sarafloxacin crystal lattice.

Near-infrared spectroscopy (NIRS) is proposed as a technique to study the mobility of water within the sarafloxacin crystal lattice. An investigation of two samples of sarafloxacin revealed that NIRS can distinguish between acceptable and unacceptable batches for formulation purposes. X-ray powder diffraction (XRPD), mid-infrared (mid-IR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) could not detect any differences between the two samples. NIRS detected differences in the location or orientation of the water molecules within the crystal lattices.

Role of an isomorphic desolvate in dissolution failures of an erythromycin tablet formulation.

The investigation of dissolution failures for erythromycin dihydrate tablet formulation over a 12-month period using a near-infrared spectroscopy technique revealed the role of a desolvated dihydrate in the retardation of dissolution. Near infrared spectroscopy (NIR) indicated a dehydrated dihydrate of erythromycin is produced during formulation and gradually binds with Mg(OH)2. The binding delays the process of dissolution. NIR was used to successfully predict that humidifying the tablets would reverse the binding and increase the dissolution rate.

Dual pH durability studies of man-made vitreous fiber (MMVF).

Dissolution of fibers in the deep lung may involve both extracellular and intracellular mechanisms. This process was modeled in vitro for each environment using an experimental flow-through system to characterize both total dissolution and specific chemical changes for three representative MMVF's: a glasswool, a slagwool, and a refractory ceramic fiber (RCF). Synthetic physiological fluids at pH 4 and at pH 7.6 were used to simulate macrophage intraphagolysosomal, and extracellular environments, respectively. Actual commercial fiber, sized to rat-respirable dimension, having an average fiber diameter of 1 micron and an average length between 15 and 25 microns, was used in the experiments. Fiber dissolution was monitored through change in chemistry of the fluid collected after percolation at a constant rate through a thin bed of sample. There are great differences in total fiber dissolution rates for the different fibers. Slagwool and RCF dissolve more rapidly at pH 4 than at pH 7.6, while the reverse is true for glasswool. Dissolution is sometimes accompanied by a noticeable change in fiber morphology or dimension, and sometimes by no change. There is strong dependency on pH, which affects not only total fiber dissolution, but also the leaching of specific chemical components. This effect is different for each type of fiber, indicating that specific fiber chemistry largely controls whether a fiber dissolves or leaches more rapidly under acidic or neutral conditions. Both total dissolution rates and calculated fiber composition changes are valuable guides to interpreting in vivo behavior of man-made vitreous fibers, and demonstrate the usefulness of in vitro acellular experiments in understanding overall fiber persistence.

Determination of temafloxacin, sarafloxacin, and difloxacin in bulk drug and dosage forms by high-performance liquid chromatography.

The fluoroquinolones, temafloxacin, sarafloxacin, and difloxacin, are determined in the bulk drug substances and in a variety of dosage form using high-performance liquid chromatography (HPLC). The HPLC system used is also applicable for ciprofloxacin and norfloxacin. The procedure uses UV detection at 280 nm, which provides a linear response of the subject compounds to at least 20 micrograms/ml. Assay precision (RSD) values were +/- 1.2% or better for the bulk drugs and ranged from +/- 0.42 to +/- 2.3% for suspension, capsule, and tablet formulations. Drug recoveries were quantitative from the dosage forms tested. Sensitivity of the subject compounds is approximately 50 ng/ml (2.5 ng on column).

Determination of spectinomycin dihydrochloride by liquid chromatography with electrochemical detection.

Spectinomycin dihydrochloride is determined by liquid chromatography with electrochemical detection. The drug is chromatographed on a reverse-phase Nucleosil C18 column using an eluent containing 0.02 M sodium citrate and 0.0015 M octyl sodium sulfate (pH 6.10 with perchloric acid) and acetonitrile (100:4). Detection is performed using a coulometric detector (porous carbon working electrode) at +0.85 V. The drug and primary degradation product are detectable. Detector response is linear to at least 20 micrograms/ml, which is four times the assay level. The procedure has relative standard deviations of +/- 1.21 to +/- 2.72% for three lots of bulk drug. Sensitivity is greater than 0.1 microgram/ml of spectinomycin (5 ng on column). Repeatability at this level is +/- 4.94%.