Drug Invention Today最新文献

Objectives

Simple, selective and precise stability indicating spectrophotometric methods were adopted and validated for the quantitative determination of Bumadizone calcium semihydrate (BUM) in presence of its alkaline degradation product (DEG I).

Methods

Method A is based on the application of first derivative (¹D) spectrophotometry, then measuring the amplitude of BUM at 245.4 nm. Method B depends on measuring the peak amplitude of the first derivative of the ratio spectra (¹DD) at 242.6, 260 and 274 nm over a concentration range of 6–20 μg mL⁻¹. Method C is isoabsorptive point spectrophotometry where total concentration of BUM and DEG I was calculated at their isoabsorptive point at 242.2 nm (Aiso) while DEG I concentration alone can be determined at λ_max 320 nm, and then BUM concentration can be determined by subtraction. In Method D ratio subtraction spectrophotometry is applied.

Results

The four methods were found to be specific for determination BUM in presence of different concentrations of DEG I and were successfully applied for the determination of BUM in Octomotol^® tablets.

Conclusion

Statistical comparison between the results obtained by applying the proposed methods and that obtained by the manufacturer one for the determination of the drug was done, and it was found that there is no significant difference between them.

Background

In the present study, a series of novel azetidinone derivatives synthesized because of its potent antimicrobial and antimycobacterial activity.

Method

Compounds (10a–10j) were synthesized by reacting Schiff's base of isoniazid reacted with, chloro acetyl chloride in presence of triethyl amine and 1, 4-dioxane as an efficient catalyst, analyzed for their structures. in vitro antimicrobial and antimycobacterial activity were carried out.

Results

Among the synthesized compounds, compound 10b and 10i was found to be the most potent against gram-positive bacteria Bacillus subtilis, gram-negative bacteria Escherichia coli, Mycobacterium tuberculosis CIP and M. tuberculosis H37Rv.

Conclusion

A series of novel azetidinone derivatives of biological interest were synthesized and analyzed, suggests that it an interesting compound compared to the current therapeutic agents and are considered to investigate further for the same.

Objectives

To develop a reverse phase high performance liquid chromatographic method for validation and quantitative estimation of the synthesized drug rasagiline hemitartrate in bulk form.

Methods

Rasagiline hemitartrate was synthesized and characterized by spectral (Infrared, Proton Nuclear Magnetic Resonance and Mass) as well as elemental analysis. Chromatographic separation was conducted on Agilent TC-C18 (250 × 4.6 mm, 5 μm) column at ambient temperature using mixture of 20 mM potassium dihydrogen orthophosphate buffer (pH 7.0): methanol and acetonitrile in the ratio (30:30:40 v/v) as a mobile phase and at a flow rate of 1.0 mL/min, while UV detection was performed at 285 nm. In addition to LOD and LOQ, other analytical parameters viz., linearity, precision, accuracy, ruggedness and robustness were detected by following the ICH (International Conference on Harmonization) guidelines.

Results

The retention time for rasagiline hemitartrate was found to be 4.30 ± 0.05 min. The method was found to be linear in the range of 10–50 μg/mL. The limit of detection and quantization for rasagiline hemitartrate are found to be 0.651 and 1.972 μg/mL respectively. Analytical recovery was 100.47%. The percentage RSD for precision and accuracy of the method was found to be less than 2%. Correlation coefficient was found to be 0.9952.

Conclusion

In this study, simple, sensitive, accurate and reliable RP-HPLC method was developed and validated as per the ICH guidelines for the determination of the synthesized drug rasagiline hemitartrate in bulk form.

Objective

This study evaluated the effect of carvedilol (CRV) commonly used antihypertensive drugs on the antiepileptic drug sodium valproate (SVP) along with neurobehavioural co-morbidities in various models of epilepsy.

Methods

For this purpose, we used the Increasing Current Electroshock Seizure (ICES) test and Pentylenetetrazole (PTZ) test in mice. Additionally, adverse effects of combined treatment with the drugs in the Spontaneous Alternation Behavior (SAB) and rotarod were assessed. The levels of TBARS and the Reduced Glutathione (GSH) were determined in brains of mice for investigation of the oxidative stress. All drugs were administered orally.

Results

SVP (50 & 100 mg/kg) and CRV (1.25, 2.5 & 5.0 mg/kg) alone as well as in combination significantly enhanced the seizure threshold in the ICES test and PTZ test. CRV significantly increase the percentage alternation scores as compared to control group whereas combination of SVP with CRV did not affect the percentage alternation scores. In the present study, CRV and SVP alone as well as in combinations had no significant effect on motor parameters, at any of the given doses. CRV and SVP alone as well as in combination shown to inhibit the lipid peroxidation and increase in the level of GSH in brain tissue in a dose dependent manner which showed that it reduces the oxidative stress.

Conclusion

The current study suggests that CRV potentiate the anticonvulsant activity of VPA. Therefore, the observed interaction could be pharmacodynamics in nature.

Objectives

To synthesize a new series of indazole substituted-1,3,4-thiadiazole derivatives 7(a-l) and test the anticonvulsant activity against maximal electroshock (MES) seizure model in male Wistar rats.

Methods

New compounds were synthesized by the reaction of indazole substituted-1,3,4-thiadiazoles with various sulfonyl chlorides. The purity of the compounds was confirmed on the basis of their elemental analysis. Chemical structures of all the new compounds were established by ¹H NMR and mass spectral data. Anticonvulsant study was done by MES seizure model and rotorod method was employed to determine the neurotoxicity.

Results

All the compounds were synthesized in good yield. Out of twelve compounds, 7b and 7d are found to be most potent of this series. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg).

Conclusions

The results obtained justify the usage of these compounds from their promising anticonvulsant activity. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the anticonvulsant activity and neurotoxicity of these compounds.

Objectives

Optimized formulations were subjected to various In vivo studies like anti-inflammatory activity, Nickel induced dermatitis and irritation study. Clobetasol propionate (CP) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the present work was to test the hypothesis that the addition CP in nanoemulsions would result in enhancement CP delivery and leading to better antipsoriatic activity.

Materials and methods

Nanoemulsions were prepared by aqueous phase titration method, using eucalyptus oil, Tween 20, ethanol, and distilled water as the oil phase, surfactant, co-surfactant and aqueous phase, respectively.

Results and discussion

We developed a topical O/W nanoemulsion in which drug is incorporated in disperse phase of oil and evaluated its efficacy against different types of in vivo studies. It was also found that the significantly increased their anti-inflammatory activity. It was reported that CP-loaded nanoemulsion significantly increased NTPDase (Nucleoside triphosphate diphosphohydrolases) activity in lymphocytes. This membrane protein is responsible for the hydrolysis of extracellular ATP (Adenosine triphosphate) which is responsible for cell proliferation, differentiation and inflammatory processes. In vivo irritation studies did not show any irritation in spite of having high amount of surfactant.

Conclusion

On the basis of above in vivo study we conclude that developed nanoemulsion is safe for human use because it has good anti-inflammatory action and did not show any irritation to the skin. All though nanoemulsion contain high amount of surfactant in comparison to cream.

Objectives

The present study has been undertaken to synthesize silver doped zinc oxide nanoparticles, with pharmaceutical importance. The synthesized particles have been evaluated to study the effect of silver doping on grain size and further on antibacterial activities against the microorganisms Bacillus subtilis and Staphylococcus aureus.

Methods

Silver doped zinc oxide nanoparticles were prepared by the solution route spin-coating process, using zinc acetate (Zn(CH₃COO)₂.2H₂O) and silver nitrate (AgNO₃) as host and dopant precursors respectively. The antibacterial activity of the silver doped zinc oxide were studied against S. auerus and B. subtilis via using agar well diffusion method.

Results & discussion

: The structure of the powder samples was analyzed by X-ray diffraction (XRD). The effect of silver doping on grain size and further on antibacterial activity against the microorganisms B. subtilis and S. auerus is discussed.

Conclusion

It was clear from X-ray investigations that its structure is wurtzite type and that an increase in Ag-doping resulted in decrease in the grain size of the ZnO nanoparticles. Antimicrobial study against the microorganisms B. subtilis and S. auerus shows that in case of S. auerus the MIC varies with increase in Ag content but in case of B. subtilis the MIC remained constant for all concentration of Ag.

Aquaculture is the world's fastest growing food production sector. However, fish culture is currently suffering from serious losses due to infectious diseases. The use of antimicrobial drugs, pesticides and disinfectant in aquaculture disease prevention and growth promotion has led to the evolution of resistant strains of bacteria. Thus, the research into the use of probiotics for aquaculture is increasing with the demand for environment – friendly sustainable aquaculture. The benefits of such supplements include improved feed value, enzymatic contribution to digestion, inhibition of pathogenic microorganisms, anti-mutagenic and anti-carcinogenic activity, and increased immune response. These probiotics are harmless bacteria that help the well being of the host animal and contribute, directly or indirectly to protect the host animal against harmful bacterial pathogens. The use of probiotics in aquaculture has just begun, due to the fact that gastrointestinal microbiota of aquatic organisms has been poorly characterized, and their effects are not studied extensively. This review summarizes and evaluates brief knowledge about the probiotic organism, the action of probiotic in fish culture and the safety evaluation of probiotics in aquaculture.

Background

To investigate the in vitro antiviral and cytotoxic activities of methanolic extract of Cassia auriculata flowers in HeLa, Vero, CRFK and HEL Cell lines.

Methods

Polarity based cold maceration method was adopted for the extraction of flowers and the antiviral activity was assessed against herpes simplex-1 and 2, vaccinia, vesicular stomatitis, cox sackie, respiratory syncytical, feline corona, feline herpes, para influenza, reo-1, sindbis and punta toro viruses in different cell lines, such as Hel, HeLa, Crandell Reus feline kidney and Vero cell cultures. In parallel the cytotoxicity was evaluated by MTT assay method.

Results

The methanolic extract possesses the strongest antiviral activity against herpes simplex-1(EC₅₀ = 50 μg/ml) and 2 (EC₅₀ = 45 μg/ml) viruses and moderate activity for remaining viruses (EC₅₀ = >100 μg/ml). The cytotoxicity results revealed that the extracts exhibited cytotoxicity above the range of 100 μg/ml.

Conclusion

The tested methanolic extract displayed an important source of anti-herpetic compound against the double stranded DNA enveloped Herpes simplex virus (HSV-1 and II), further studies are needed to identify the exact compound for their antimicrobial action.

Objective

Osteomyelitis is a multibacterial bone infection which is still remains challenging and difficult to treat, despite of advances in antibiotics and new operative techniques. Present study aims at formulating Gentamicin implants in treatment of Osteomyelitis & other bone infections using glyceryl monostearate (GMS) matrices as a carrier.

Methods

Gentamicin implants were prepared by using combination of glyceryl monostearate and poly ethylene glycol as hydrophobic biodegradable sustained release matrices along with different percentage of Sorbitol and Tween80 as erosion enhancers. Several formulations were prepared (K1–K7) by melt granulation followed by compression to form disc shaped implants. The prepared formulations were evaluated for different in vitro parameters & optimized formulation was subjected to in vivo study.

Results & discussion

Formulation K4 shows excellent cumulative drug release profile and it does not completely lose its physical shape even after 28 days thus this formulation conclude to be optimum formulation among the all GMS based implant formulations. Also optimized GMS based implant does not show any severe signs of inflammation and other foreign body reactions in laboratory animals, thus it was concluded that GMS based implant have acceptable biological compatibility even after 28 days.

Conclusion

Therefore from this study it is proved that, the glyceryl monostearate based implants have potential to retard the drug release for more than five weeks in the treatment of osteomyelitis & bone infections.