Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers

Ofloxacin (OFX) is a synthetic broad spectrum analog of second generation fluoroquinolone antibiotic. It is used for the treatment of urinary tract, prostate, skin, urinary and respiratory tract infections. Ornidazole (ORN) is a nitroimidazole derivative. It is used in the treatment of bacterial vaginosis, trichomoniasis, amoebiasis, giardiasis and infections due to anaerobic bacteria. These drugs are highly soluble in acidic media and precipitates in alkaline media thereby losing its solubility. Hence we attempted to develop a gastro retentive floating matrix type drug delivery system for Ofloxacin and Ornidazole in combined dosage form with hydroxyl propyl methyl cellulose (HPMC) K15M, HPMC K100M and polyethylene oxide 18NF (PEO). The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. The prepared floating drug delivery systems were evaluated for physicochemical characteristics, mainly in vitro release and in vivo residence time by radiographic studies. The best formulation (F2) was selected based on in vitro release and physicochemical characteristics and used in vivo radiographic studies by incorporating BaSO4. These studies revealed that tablets 300 ± 30 minutes in healthy human volunteers in fasting state and indicated that the gastric retention was increased by floating principle. By fitting the data into zero order, first order and Higuchi models, it was concluded that drug release from matrix tablets followed Higuchi model and the mechanism of drug release was diffusion mediated. Based on the physical evaluation, in vitro drug release and in vivo characteristics, it was concluded that for potential therapeutic use, suitable for the development of a floating drug delivery system of Ofloxacin and Ornidazole in combined dosage form

Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers

Ofloxacin (OFX) is a synthetic broad spectrum analog of second generation fluoroquinolone antibiotic. It is used for the treatment of urinary tract, prostate, skin, urinary and respiratory tract infections. Ornidazole (ORN) is a nitroimidazole derivative. It is used in the treatment of bacterial vaginosis, trichomoniasis, amoebiasis, giardiasis and infections due to anaerobic bacteria. These drugs are highly soluble in acidic media and precipitates in alkaline media thereby losing its solubility. Hence we attempted to develop a gastro retentive floating matrix type drug delivery system for Ofloxacin and Ornidazole in combined dosage form with hydroxyl propyl methyl cellulose (HPMC) K15M, HPMC K100M and polyethylene oxide 18NF (PEO). The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. The prepared floating drug delivery systems were evaluated for physicochemical characteristics, mainly in vitro release and in vivo residence time by radiographic studies. The best formulation (F2) was selected based on in vitro release and physicochemical characteristics and used in vivo radiographic studies by incorporating BaSO4. These studies revealed that tablets 300 ± 30 minutes in healthy human volunteers in fasting state and indicated that the gastric retention was increased by floating principle. By fitting the data into zero order, first order and Higuchi models, it was concluded that drug release from matrix tablets followed Higuchi model and the mechanism of drug release was diffusion mediated. Based on the physical evaluation, in vitro drug release and in vivo characteristics, it was concluded that for potential therapeutic use, suitable for the development of a floating drug delivery system of Ofloxacin and Ornidazole in combined dosage form

Development and validation of new analytical method for the estimation of fluoxetine in bulk and dosage form by UV spectrophotometry

A simple, rapid and precise method is developed for the quantitative determination of Fluoxetine in combined pharmaceutical-dosage forms. The method was based on UV Spectrophotometric determination of Fluoxetine drug using Beer-Lamberts Law. It involves absorbance measurement at 224 nm (λmax of Fluoxetine) in water. For UV Spectrophotometric method, linearity was obtained in concentration range of 5-30 mcg/ml with regression 0.999 for Fluoxetine respectively. Recovery was in the range of 98 -102%; the value of standard deviation and %R.S.D was found to be < 2 shows high precision of the method.

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Role of fluid on seismicity of an intra-plate earthquake zone in Western India: an electrical fingerprint from magnetotelluric study

Abstract The magnetotelluric (MT) investigation carried out in Koyna Seismogenic Zone (KSZ), an intra-plate earthquake region in Western India, along an E–W profile brings out moderately conductive (~ 700–1000 Ωm) near vertical features within the very high resistive (> 20,000 Ωm) granite/granite-gneiss basement. Occurrences of these anomalous moderate conductors are corroborated with sensitivity analysis. The alignment of earthquake hypocenters along the resistive–conductive boundary signifies the moderate conductor as basement fault. The conversion of resistivity values to the ratio of seismic P- to S-wave velocity (v p/v s) suggests that the moderate conductivity of the fault zone (as compared to the surrounding basement) appears due to the presence of fluid in the fault zone. Geophysical evidences reveal ~ 2.5–3.6 vol% fluid in the fault zone with ~ 1.8–2.6% interconnected porosity, which migrates along the structural boundary and invades the mechanically strong basement to nucleate the brittle failure within it. The present study proposes two mechanisms for the seismicity in the Koyna region. First: the meteoric water circulation due to the loading–unloading of nearby Koyna reservoir acts as potential fluid source for this triggered seismicity, which has also been suggested by previous studies. Second: the fluid circulation due to a deep-seated source. The present MT study brings out a conductive feature below 20 km depth which is thought to be emerged due to the dehydration of amphibole bearing rocks. The fluid generated from dehydration might act as a probable source to the triggered seismicity; since the conductive feature has a linkage to the upper crust. Graphical Abstrac

Integrated subsurface investigation for magmatic sulfide mineralization in Betul Fold Belt, central India

Magnetotelluric (MT), Electrical Resistivity Tomography (ERT), Time-Domain Induced Polarization (TDIP), Geochemical and Geological studies followed by drilling and down-hole logging were undertaken with in the Betul Fold Belt (BFB) in Central India, to demarcate zones of magmatic Ni-Cu-PGE sulfide mineralization. The BFB is predominantly composed of circular to elongate gabbro bodies of the Padhar Mafic-Ultramafic Complex, intruded into a sequence of bimodal volcanic rocks and quartzites. Near-surface samples of ultramafic rocks were subjected to precise geochemical analysis and scanned by an electron microscopy with an energy dispersive spectrometer (SEM-EDS). This work indicated the presence of pyrite, pyrrhotite, chalcopyrite, pentlandite, and minor amounts of W-Cd bearing boweiite and palladenite assemblage. These minerals are regarded as favorable to the occurrence of Ni-Cu-PGE sulfide mineralization. MT data derived from two profiles were analyzed and modeled using 2D and 3D inversion algorithms. The robust conductivity anomalies obtained from the MT model have been interpreted coupled with electrical tomography, geology, and geochemistry data. The near-surface shallow depth conductors observed in the ERT sections are interpreted as the sulfide mineralized zones. They corroborate the MT results. These conductive zones reflect the occurrence of the magmatic Ni-Cu-PGE bearing sulfide mineralization associated with rocks of the mantle-derived Padhar Mafic Ultramafic Complex. This geophysical data, in conjunction with petrological and geochemical analysis of drill core samples have allowed the identification of the origin and paragenesis of sulphide mineralization in the study area. Geochemical studies suggest that the parental magma was generated from a subduction modified, metasomatized and an enriched mantle source that was subsequently emplaced in a magmatic continental arc setting. The interpreted conductors, observed at shallow depths (similar to 200-300 m), have been generated by secondary hydrothermal fluid circulation leading to vein formation in the host Padhar Mafic-Ultramafic Complex. The MT and electrical tomography models delineate the geological boundaries of the sulfide-bearing mineralized deposits in the BFB