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The objective of the current study was to develop a simple, precise and accurate RP-HPLC assay method and its validation for determination of ambrisentan in pharmaceutical tablet dosage form. Gradient RP-HPLC separation was achieved on an analytical Primsil C18 R column (250 mm x 4.6 mm; 5 pm particle size) using mobile phase containing mixture of acetonitrile: water (65:35 V/V). The developed method was validated for specificity, linearity, precision, accuracy and robustness study. The method was linear in the drug concentration range of 10-50 µg mL-1 with a correlation coefficient 0.998. The percent RSD values were found to be less than 2 %, indicating the developed method was also robust. The method was completely validated and shows satisfactory result for the all method parameter. Hence it is concluded that the proposed method is precise, simple, sensitive, accurate, rugged and rapid and can be applied successfully for the estimation of ambrisentan in pharmaceutical dosage form. [ABSTRACT FROM AUTHOR]

Acitretin is the drug of choice for the treatment of psoriasis, but due to its poor solubility, the development of oral and topical formulations of acitretin has been restricted. The aim of the present investigation was to enhance the solubility of acitretin. Solid dispersions of acitretin were prepared using a lipidic solubilizer, Gelucire® 44/14. These solid dispersions were characterized through FT-IR, DSC, XRD, drug content and solubility studies. The most solubilized dispersion was loaded on an N,N-methylenebisacrylamide microporous cryogel. Physical parameters of the solubilized drug such as the porosity, rheological behaviour, surface properties, appearance, drug content and diffusion behaviour were studied. It was concluded that the solubilized form of acitretin, loaded on a surface-modified cryogel, is the best option for the treatment of psoriasis. The hydration of the skin was excellent, and the permeability of the acitretin into the skin was better. [ABSTRACT FROM AUTHOR]

Oral conventional formulations like tablets, capsules and liquids have many limitations. Due to this and patient incompliance, there is a need to develop new formulations with better efficiency and stability. The aim of the present study was to develop and optimize fast dissolving Oro-dispersible strips (ODS) of isosorbide mononitrate by 3²-full factorial design. HpMC E15 (X1) concentration and glycerin (X2) concentration were selected as the independent variables, whereas, in vitro disintegration time (Y1), percent drug release (Y2) and tensile strength (Y3) were selected as dependent variables. Fast dissolving Oro-dispersible strips of isosorbide mononitrate were prepared by the solvent casting method.Tensile strength, disintegration time and in vitro dissolution of ODS of the strip were found to be within accepted range for optimized formulation. Statistical validity of the polynomials was established by ANOVA using Design-Expert software. The study suggests isosorbide mononitrate fast dissolving Oro-dispersible strip as potential alternative dosage form in management of angina pectoris. [ABSTRACT FROM AUTHOR]

Drug release properties for transdermal route can be better modified as per requirement which is mostly dependent upon the carrier system. In case of organic film-forming systems, the physical properties may not be achieved for successful delivery of drug through transdermal route. A novel organic-inorganic hybrid film-forming gel may fulfil these expectations to many extend. The present study focuses on the development of the organic-inorganic hybrid film-forming gel. A smooth, transparent, clear film-forming gel of tramadol was prepared for application on the intact skin with better comfort and modified drug release rate properties. The key properties of the adhesive films produced from the hybrid gels were investigated and the results showed that the incorporation of appropriate PVA: TEOS: Glycerine: HCl in the ratio of 46:12.5:25.5:6 respectively. Resultant hybrid film-forming gel has modified the physical properties and improved drug release properties. Furthermore, the investigations of skin irritation suggested no irritation to skin after topical application. This study has provided an alternative to the presently available organic gel and films for transdermal delivery of drugs with better patient compliance and modified physical and chemical stability. [ABSTRACT FROM AUTHOR]

AbstractEmpagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has recently reported to prevent the depression in chronic animal model. The present study aimed to explore the antidepressant potential of empagliflozin using a neuroinflammation-mediated depression involving the olfactory bulbectomy (OBX) model in diabetic rats. A low dose of streptozotocin was injected to induce diabetes in all group of animals. Following the confirmation of hyperglycemia, OBX surgery was performed. Post-surgery, the drug treatments were administered orally for 14 consecutive days. The study evaluated the effects of daily oral administration of empagliflozin at doses of 5 and 10 mg/kg, alongside metformin (200 mg/kg) and clomipramine (50 mg/kg), on OBX-induced behavioral depression in rats. Separate sham and vehicle control groups were also maintained. Behavioral parameters in open field, forced swim test, elevated plus maze and splash test were recorded on 28th day. Results showed that empagliflozin, at the higher dose, significantly enhanced behavioral outcomes, evidenced by increased distance travelled, greater open arm entries, and reduced immobility, alongside a notable reduction in grooming time. Moreover, empagliflozin significantly restored the antioxidants level specifically Glutathione (GSH) and Catalase (CAT) in OBX insulted rat brain and decreased Lipid peroxidase (LPO). Notably, molecular docking study demonstrated a good binding affinity of empagliflozin for Brain-Derived Neurotrophic Factor (BDNF), suggesting that its antidepressant effects may be mediated through the modulation of the BDNF pathway. These findings support the potential therapeutic application of empagliflozin for depression, particularly in cases associated with neuroinflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Targeting Hec1/Nek2 is considered as crucial target for cancer treatment due to its significant role in cell proliferation. In pursuit of this, a series of twenty-five 2-aminothiazoles derivatives, along with their Hec1/Nek2 inhibitory activities were subjected to QSAR studies utilizing QSARINS software. The significant three descriptor QSAR model was generated, showing noteworthy statistical parameters: a correlation coefficient of cross validation leave one out (Q 2 LOO ) = 0.7965, coefficient of determination (R 2 ) = 0.8436, (R 2 ext) = 0.6308, cross validation leave many out (Q2 LMO ) = 0.7656, Concordance Correlation Coefficient (CCC CV  = 0.8875), CCC tr  = 0.9151, and CCC ext  = 0.0.7241. The descriptors integral to generated QSAR model include Moreau-Broto autocorrelation, which represents the spatial autocorrelation of a property along the molecular graph's topological structure (ATSC1i), Moran autocorrelation at lag 8, which is weighted by charges (MATS8c) and RPSA representing the total molecular surface area. It was noted that these descriptors significantly influence Hec1/Nek2 inhibitory activity of 2-aminothiazoles derivatives. New lead molecules were designed and predicted for their Hec1/Nek2 inhibitory activity based on the developed three descriptor model. Further, the ADMET and Molecular docking studies were carried out for these designed molecules. The three molecules were selected based on their docking score and further subjected for MD simulation studies. Post-MD MM-GBSA analysis were also performed to predicted the free binding energies of molecules. The study helped us to understand the key interactions between 2-aminothiazoles derivatives and Hec1/Nek2 protein that may be necessary to develop new lead molecules against cancer.Communicated by Ramaswamy H. Sarma.