Identification, synthesis, and characterization of β-isomer as process related impurity in production of methocarbamol from guaifenesin

Methocarbamol is a central nervous system depressant with skeletal muscle relaxant properties indicated to treatspasms. During the synthesis of methocarbamol from guaifenesin, both potential known and an unknown impurity(0.05%–0.1%), high performance liquid chromatography) were observed. The later was separated using preparativeliquid chromatography. Upon the findings of the 1H nuclear magnetic resonance, Mass, and IR spectral analysis, theunknown impurity was designated as a β-isomer of methocarbamol [1-hydroxy-3-(2-methoxy phenoxy) propan-2-ylcarbamate]. The impurity isolation, its structure elucidation, and the potential formation mechanism are discussed.

Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system.

Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.

Detection of Enterobacteriaceae producing CTX-M extended spectrum beta-lactamases from a tertiary care hospital in south India.

A total of 23 clinical isolates (15 Escherichia coli and 8 Klebsiella pneumoniae), resistant to cefotaxime and ceftazidime recovered during 2002 and 2003, were investigated for production of CTX-M extended spectrum beta-lactamase (ESBL) by phenotypic and molecular methods. The presence of ESBL was tested by NCCLS phenotypic confirmatory test using cephalosporin/clavulanate combination discs and E-test ESBL strips. Determination of MIC of cefotaxime and ceftazidime was done with and without the presence of clavulanic acid by agar dilution technique. Polymerase chain reaction revealed the presence of CTX-M type ESBLs in 19 isolates. Further sequencing resulted in identification of CTX-M-15 ESBLs. This is the first report identifying CTX-M type ESBL from clinical isolates of E. coli and K. pneumoniae from a tertiary care hospital in south India.