INCLUSION STUDIES ON α-CYCLODEXTRIN COMPLEXES OF GLIPIZIDE AND GLICLAZIDE WITH EFFECT OF PH

Objective: To synthesize inclusion complexes of oral antidiabetic drugs, i.e., Glipizide (GP) and Gliclazide (Glc) with a-cyclodextrin (α-CD) and varying the pH which will enhance the solubility and thereby oral bioavailability of the drugs.Methods: Liquid inclusion complexes were prepared and characterized by ultraviolet-visible (UV-VIS) spectroscopic studies, and fluorescent studies solid inclusion complexes of GP and Glc with α-CD were prepared by co-evaporation method and characterized by differential scanning calorimetric studies (DSC) and1H nuclear magnetic resonance spectroscopic studies (1H NMR).Results: The inclusion complexes of both GP and Glc with α-CD showed high binding constant values for pH 2 from the UV-VIS spectroscopy studies and fluorescent studies. DSC and1H NMR spectroscopic studies confirmed the inclusion of GP and Glc inside the α-CD cavity.Conclusion: Formed with more stable inclusion complexes, with α-CD are GP and Glc at pH 2, along with pH modulation could be a suitable strategy to enhance the solubility and oral bioavailability of both the drugs.Keywords: Solubility, Bioavailability, Glipizide, Gliclazide, Inclusion complexes, α-Cyclodextrin.Â

ANALYTICAL METHODS FOR THE DETERMINATION OF AMINOGLYCOSIDES ANTIBIOTICS BY CHROMATROGRAPHIC TECHNIQUE

Aminoglycosides antibiotics are considered to be the antimicrobial agents used frequently in the treatment of human diseases caused by a bacterial infection. Most of the aminoglycosides antibiotics are highly polar in nature and they are lacking the UV absorbing chromophore in the molecules. The present articles accentuate the analytical method associated with the analysis of aminoglycosides molecules. Various chromatographic techniques like liquid chromatography, gas chromatography; mass spectrometry were used for the detection of aminoglycosides antibiotics. However, due to its limitation in the ultraviolet-visible spectrophotometry (UV/Vis) technique, different types of detection techniques like corona-charged aerosol detector (CAD), electrochemical detector (ECD) were used as a most powerful and versatile technique for the demonstration of these molecules in the analytical field. Analytical methods help to ensure the quality of the drug products. This review paper is devoted to providing an overview of the key performance technique used for the application and detection of these aminoglycosides molecules

Phytopharmaceutical Studies of Selected Medicinal Plants Subjected to Abiotic Elicitation (Stress) in Industrial Area

Plants are a source of large amount of drugs comprising antispasmodics, emetic, Anti-cancer, anti microbial and anticancer activities etc. A large number of the plants are claimed to possess the antibiotic properties in the traditional system and today they are extensively used by the people and the metal Components in the plants grown in polluted area seemingly increase the concentration of phytochemicals. Recent times the flora and fauna of any region is directly or indirectly exposed to the all types pollutants which may result into adverse effects rarely the metal pollutants may trigger the production of phytochemicals. The present study deals with Industrial pollution of the area selected for study, metal up take, and their effect on phytochemical, antimicrobial and anticancer activities that explore the research on five medicinal plants namely Adhatoda vasica, Eucalyptus globulus, Hyptis suaveolens, Ricinus communis and Tinospora cordifolia that thrive well and grow luxuriantly in industrial polluted area and the same five plants from natural area of Visakhapatnam District. The aim of this study is to analyze the effect of Metal elements on phytochemical productivity and antimicrobial and anticancer activity of these medicinal plants. Metal analysis is done ICP-MS (PerkinElmer Sciex Instrument, model ELAN DRC II, USA). Alkaloids, flavanoids, terpenoids and phenols screening is done in solvents Hexane, Chloroform and methanol and checked for antimicrobial activity and anti-cancer activity of Eucalyptus globulus and Tinospora cordifolia were determined by XTT assay on MCF-7 cell lines. The results are discussed in comparison of Natural with pollutant grown plants. The plants that showed better production of phytochemicals due to the presence of metal elements could be recommended to phytopharmaceutical industries as they comparatively showed better production of phytochemicals further proposing a definite way to eliminate toxic metals from them

Potential role of BRCA1 protein expression as a prognostic tissue biomarker in breast carcinoma: An immunohistochemical and clinicopathologic study from South India

Introduction. BRCA1 dysfunction is a hallmark of both hereditary and sporadic breast cancer. BRCA1 protein expression can be lost by germline mutation, somatic mutation or promoter hypermethylation. This study aimed to explore BRCA1 dysfunction in breast cancer patients by immunohistochemistry and to study its association with prognostic factors. Material and methods. BRCA1 protein expression was assessed by immunohistochemistry on formalin fixed paraffin embedded tissue blocks of 110 invasive breast carcinoma patients. Furthermore, the clinical findings and tumor features associated with BRCA1 dysfunction were characterized. Results. Reduced BRCA1 immunoreactivity was observed in 19% of breast cancer cases. Although these patients presented with aggressive tumor characteristics, statistical significance was observed only with presence of lymphovascular emboli (p < 0.05). These results suggest that loss of BRCA1 protein expression is associated with an aggressive phenotype of breast carcinoma. Conclusions. Immunohistochemistry for BRCA1 protein expression in tumor tissues may provide a less expensive screening tool to identify BRCA1 dysfunction due to genetic or epigenetic alterations

Investigation of various practical techniques to enhance dissolution of ezetimibe from oral tablets: A comparative study

ABSTRACT Objective: The aim of this work was to investigate and compare various practical techniques to enhance dissolution of ezetimibe, a Class II Biopharmaceutics Classifi cation System compound. Ezetimibe is a poorly soluble compound with variable oral bioavailability. Nanosuspensions, hydroxypropyl-beta-cyclodextrin (HPβCD) complexes as well as combination of surfactant were techniques investigated. Materials and Methods: Nanosuspension of ezetimibe was prepared using solvent-antisolvent precipitation technique. The nanosuspensions were characterized by powder X-ray diffractometry and scanning electron microscopy. HPβCD inclusion complexes were prepared using physical mixture, co-evaporation, and kneading methods. These complexes were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Ezetimibe tablet formulations containing drug nanosuspensions, HPβCD complexes as well as sodium lauryl sulfate (SLS) enrichment were prepared and evaluated for dissolution. Results and Discussion: Nanosuspensions of ezetimibe with a mean particle size of 900 nm were successfully prepared using solvent-antisolvent precipitation. FTIR and DSC studies confi rmed the formation of ezetimibe inclusion complexes. Tablets prepared using pure drug showed very poor dissolution. In contrast, tablets of nanosuspensions, HPβCD inclusion complexes and SLS mixtures showed enhanced dissolution. The tablets prepared using nanosuspensions demonstrated enhanced dissolution rate when compared to the formulations prepared using HPβCD complexes and SLS enrichment. All the techniques investigated can be used to enhance the dissolution of ezetimibe and thus can enhance the oral bioavailability and also reduce the fl uctuations in the oral bioavailability. Conclusion: The techniques that were employed in this present work, nanosuspensions seem to be better when compared to cyclodextrin inclusion complexes and SLS enrichment in enhancing solubility and dissolution rate of ezetimibe

Identification and benchmarking of Myokinasib-II as a highly selective and potent chemical probe for exploring MLCK1 inhibition

Deciphering functional relevance of every protein is crucial to developing a better (patho)physiological understanding of human biology. Discovery and use of quality chemical probes propel exciting developments for developing drugs in therapeutic areas with unmet clinical needs. Myosin Light Chain Kinase (MLCK) serves as a possible therapeutic target in a plethora of diseases, including inflammatory diseases, cancer etc. Recent years have seen substantial increase in interest in exploring MLCK biology. However, there is only one widely used MLCK modulator, namely ML-7, that too with a narrow working concentration window and high toxicity profile leading to limited insights. Herein, we report the identification of a potent and highly selective chemical probe, Myokinasib-II, from the synthesis and structure-activity relationship studies of a focussed indotropane-based compound collection. Notably, it is structurally distinct from ML-7 and hence, meets the need for an alternative inhibitor to study MLCK biology as per the recommended best practices. Moreover, our extensive benchmarking studies demonstrate that Myokinasib-II displays better potency, better selectivity profile and no non-specific interference in relevant assays as compared to other known MLCK inhibitors