Sachin

The purpose of this study was to develop chitosan based anastrozole nanoparticles for treatment of breast cancer. An ionic gelation method was used to prepare anastrozole controlled-release nanoparticles. A 32 full factorial design was employed. Experimental variables such as concentration of CS and cross-linking agent sodium TPP were varied to study their effect on drug entrapment efficiency and release rates of drug from nanoparticles. Fourier transform infrared spectroscopic (FTIR) analysis and differential scanning calorimetry (DSC) were employed to determine any interactions between drug and polymer. The FTIR studies revealed no chemical interaction between the drug and the polymer. Entrapment efficiency of nanoparticles ranged between 51.51 ± 0.81 % to 84.35 ± 1.06 %.In-vitro release studies were performed in phosphate buffer saline of pH 7.4. A slow release of anastrozole up to 72 h was observed. Mean particle size of nanoparticles ranged between 1635 nm to 72.30 nm with mean particle size of 273.6 nm, while zeta potential 0.52 mV. DSC results indicated that the anastrozole entrapped in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. Scanning electron microscopy was done to study the surface morphology. Results revealed that more spherical shaped particles with possible aggregation. The highest correlation coefficients were obtained for the Higuchi model, suggesting a diffusion mechanism for the drug release. The results demonstrated that anastrozole nanoparticles with chitosan could be an alternative delivery method for the long-term treatment of breast cancer.

The aim of the study was to assess Pharmacognestic study of crude plant extract of Rivea hypocrateriformis and was carried out to characterize the chemical composition of some constituents by GC-MS analysis. Different solvent extracts (aqueous, methanolic, chloroform, ethyl acetate and DMSO) of plant R. hypocrateriformis leaves were assessed for in vitro antimicrobial activity assay by disc diffusion method furthermore antioxidant assay was carried out DPPH free radical scavenging activity, Phytochemical screening was carried out by ‘guide to modern techniques of plant analysis” and GC-MS analyses were performed to identify the constituents present in the plant that stand behind such activities. Due to higher polarity, DMSO extract show revealed presence of maximum phytochemical composition susceptibility as well as methanol and chloroform shows average amount of phytoconstituents. The antibacterial screening is the major of the inhibition hollow observed in inhibition zone. The highest inhibition zone was observed in DMSO extract against each bacterial strain. Where E. coli shows mid active zone inhibition and S. aureus show less, IC50 value of the sample was found to be moderate as compared to standard and the eight compounds were identified in R. hypocrateriformis leaf extract by GCMS analysis. R. hypocrateriformis plant had considerable major chemical composition present in crude extract. Due to presence of major chemical components make it seems to be important for medical purposes and plant contains Potential antibacterial components that may be useful for evolution of pharmaceutical for the therapy of ailments. Also plant extracts can be used for the treatment of infections caused by the strains of the test bacterial organisms.

In order to achieve rapid action and sustained release, we have fabricated dual type of mini-tablets of Diclofenac Sodium enclosed in a single capsule. 10 formulations of rapid release (IF1-10) mini tablets were prepared using sodium starch glycolate, Cross povidone and Micro crystalline cellulose. 12 formulations of sustained release (SF1-12) mini tablets were prepared by using HPMC, carbopol, Ethyl cellulose, xanthan gum and guar gum. All formulations were evaluated for pre-compression and post-compression parameters. Drug Excipient interaction was determined by FTIR, Short term stability studies were carried out at 40 0C /75 % RH for 3 months. Pre-formulation and studies conformed that all formulations showed better flow property. In vitro studies showed that all mini tablets in combination released more than 55 % within 30 min whereas marketed tablet Voveran SR 100 showed only 11 % release indicating the rapid drug release and the release was extended up to 80 % in 20th hour indicating the sustainability of the release. Natural polymers, Xanthan gum and guar gum containing formulations showed above 90 % in 12th hour indicating little rapid drug release when compared to synthetic polymers. FTIR report indicated no interaction of drug with excipients. Stability studies showed no significant loss in drug content, release profile and physical appearance. Hence it can be concluded that, the release profiles duel type mini tablets were quite promising for once a day formulation.

Orally disintegrating tablet are gaining popularity over conventional tablets due to their convience in administration and suitability for patients. The purpose of the research was to mask the intensely bitter taste of tramadol hydrochloride and to prepare orally disintegrating tablets for achievement of quick onset of action of the drug. Tramadol hydrochloride is an analgesic which has been prove to be efficient in managing relief from pain and including pain after surgery. In the present study an attempt has been made to prepare bitter less orally disintegrating tablet of tramadol hydrochloride using Eudragit EPO as a taste masking agent. Direct compression method was used for preparing tablet & super disintegrating agent like Crosspovidone, Crosscarmellose sodium and sodium starch glycolate were used to prepare blend and evaluated for pre-compression parameter such as bulk density, compressibility, and angle of repose etc. the prepared batches of tablets were evaluated for hardness, weight variation, friability, drug content, disintegration time and in-vitro dissolution profile was found to be satisfactory. It was found that Eudragit EPO being hydrophilic facilitated the increase in the uptake of the saliva thus showing the complimentary action of that superdisintegrant.

3-(2-bromacetyl) phenyl benzoate is key starting material used in synthesis of phenylephrine, (R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol which is selective α1-adrenergic receptor agonist used primarily as decongestant, as an agent to dilate the pupil, and to increase blood pressure. Hence the current research work was aim to synthesize a series of 3-(2-bromacetyl) phenyl benzoate  derivatives by treatment of secondary amines with carbon disulphide and 3-(2-bromacetyl) phenyl benzoate  in presence of strong base in ethanol afforded the corresponding Dithiocarbamates. Their chemical structures are characterized by 1H &13C NMR, MS, Elemental analysis, and chromatography methods (TLC). The antimicrobial activity was evaluated by their MIC and zone of inhibition by taking Penicillin, Streptomycin and Amphotericin as standard reference drugs. The microbial assay revealed that compounds D4 and D5 showed the most potent antimicrobial activity against variety of bacteria as well as fungal isolates, which may be a promising antimicrobial leading compound for the further research.

5-Hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) are implicated in modulating descending inhibitory pain pathways in the central nervous system. Milnacipran (MLN) is a selective and potent dual 5-HT and NE reuptake inhibitor (SNRI). In the present study, the effects of HMG-CoA reductase inhibitor atorvastatin (ATR) on antidepressant- induced anti-nociception have been investigated. Anti-nociceptive effects were evaluated using formalin test in rats after administration of atorvastatin and milnacipran alone as well as in combination. Fifty microlitre of 2.5% formalin solution was injected subcutaneously into the plantar surface of the right hind paw and nociceptive behavior was observed up to 45 min in the blocks of 5 min. Milnacipran induced a dose-dependent anti-nociception in the first phase as well as in the second phase of the formalin test at the dose levels of 10, 20, 40 and 60 mg/kg, p.o.. Milnacipran significantly attenuated the duration of licking and licking frequency both in second phase. Atorvastatin (1, 5, 10 and 20 mg/kg, p.o.) did not inhibit the nociceptive behavior of formalin significantly when treated alone. A combination of sub-therapeutic doses of the milnacipran (20 and 40 mg/kg, p.o.) with atorvastatin (10 and 20 mg/kg, p.o.) potentiate anti-nociception induced by antidepressant significantly. It is concluded that the atorvastatin modulate the antidepressant-induced anti-nociception in formalin induced inflammatory pain model. However, studies in chronic models of neuropathic pain are required to evaluate the efficacy of milnacipran and atorvastatin combination in rats.

High-Throughput Screening (HTS) is an approach to drug discovery that has gained widespread popularity over the last two decades and has become a standard method for drug discovery in the pharmaceutical industry. Progress from traditional one-compound-at-a time approach, low throughput screening to high throughput screening involving fully automated robotic systems, enables testing of large numbers of compounds daily for different activities in miscellaneous areas of biology. HTS reveals screening of more than 100,000 samples per day. Compared to traditional drug screening methods, HTS is characterized by its simplicity, rapidness, low cost, and high efficiency. Identification of good hits using HTS can minimize the time span of drug discovery noticeably. However, synthetic chemistry for lead optimization and the low throughput of secondary assays for defining the crucial pharmacological properties of active compounds, limits the overall rate of identification of candidate molecules for clinical evaluation. Coupling of compound library with wide chemical diversity along with HTS shows massive drug discovery potential, but to be successful screening technique it depends on several factors. These include the number and quality of validated targets, the number and diversity of compounds in the collections, and the ability to screen these in a timely and cost effective manner using robust informative assays. In this review we have discussed the types of HTS assays, assay miniaturization automation and different detection techniques like fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), homogeneous time resolved fluorescence (HTRF) etc.

Glycogen synthase kinase-3 (GSK-3) is an intermediary enzyme in various cellular pathways, and has been implicated in the Pathophysiology and treatment of numerous diseases, including Alzheimer, diabetes, and bipolar disorder. Alzheimer’s disease (AD) is a disorder without a molecular marker in peripheral tissues or a disease modifying treatment. Evidence suggest that the co-relation of diabetes and Alzheimer is clear with the GSK-3. Now day’s researchers taking efforts basically to develop the new GSK-3 inhibitors like lithium. For the development of new GSK-3 inhibitors, we have to understand its molecular mechanism and their involvement in pathological condition. So here we summarize brief introduction and mechanism of GSK-3.

Simple area under curve spectrophotometric method for determination of Cefixime and Linezolid in bulk and tablet formulation was developed and validated as per ICH guidelines. The lmax of Cefixime and Linezolid were found to be 289nm and 257nm respectively. The linearity range was found 2-12μg/ mL for Cefixime and 5-30μg/mL for Linezolid. In the tablets dosage form Cefixime and Linezolid were estimated as 99.92% and 99.94% respectively. The lower limit of detection (LOD) for Cefixime and Linezolid was found to be 0.039μg/ml and 1.11μg/ml respectively.and the limit of quantization (LOQ) was determined as the lowest concentration for Cefixime and Linezolid was found to be 0.118μg/mL and 3.37μg/ml respectively. The validated spectrophotometric method employed proved to be simple, economical, precise and accurate.

Herps zoster is a viral infection and a common disorder of the eyes. It is caused by herpes simplex virus: herpes virus type 1(HSV-1) & herpes virus type 2 (HSV-2). Topical acyclovir is currently the only and safe pharmacologic treatment of severe viral infection of the eyes. Nanoparticulate formulations have advantage of improving residence time over ocular surface, reduced size increasing permeation across corneal surface for intraocular activity. The objective of this study was to prepare and evaluate Acyclovir (Acy)  nanoparticles (NPs) for the treatment of Herps zoster infection of the eyes. So, the present study was designed with the primary aim to prepare nanoparticles by nanoprecipitation method using cationic polymer Eudragit E100 and secondly to study the effect of variables on the behaviour of nanoparticles. Preliminary study showed the compatibility of the drug with the formulation. Optimization was done using full factorial design with independent variables such as Drug to polymer ratio, Organic: aqueous phase ratio and effect of type and concentration of stabilizer. The dependent variables were determined such as particle size, drug entrapment, % drug release selected as the levels. F21 formulation was selected as the final optimized formulation.