Amit Kundu

Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats.

Olmesartan medoxomil (OM) is hydrolyzed to its active metabolite olmesartan by the action of aryl esterase to exert its antihypertensive actions by selectively blocking angiotensin II-AT1 receptor. Poor aqueous solubility and uncontrolled enzymatic conversion of OM to its poorly permeable olmesartan limits its oral bioavailability. The aim of the current study was to formulate a novel nanoemulsion of OM to improve its pharmacokinetics and therapeutic efficacy. The oil-in-water (o/w) nanoemulsion of OM was developed using lipoid purified soybean oil 700, sefsol 218 and solutol HS 15. We have characterized the nanoemulsions by considering their thermodynamic stability, morphology, droplet size, zeta potential and viscosity and in vitro drug release characteristics in fasting state simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.5). The thermodynamically stable nanoemulsions comprises of spherical nanometer sized droplets (<50 nm) with low polydispersity index showed enhanced permeability through the Caco-2 cell monolayer. The concentration of active olmesartan in rat plasma following oral absorption study was determined by our validated LC-MS/MS method. The result of the pharmacokinetic study showed 2.8-fold increased in area under the curve (AUC0-27) of olmesartan upon oral administration of OM nanoemulsion and sustained release profile. Subsequent, in vivo studies with nanoemulsion demonstrated better and prolonged control of experimentally induced hypertension with 3-fold reduction in conventional dose. By analysing the findings of the present investigations based on stability study, Caco-2 permeability, pharmacokinetic profile and pharmacodynamic evaluation indicated that the nanoemulsion of OM (OMF6) could significantly enhance the oral bioavailability of relatively insoluble OM contributing to improved clinical application.

Rationalized design, synthesis and pharmacological screening of amino acid linked spiro pyrrolidino oxyindole analogs through environment friendly reaction

Introduction: The development of newer synthetic approaches toward the synthesis of polynuclear heteroaromatics and their application in the synthesis of some biologically active compounds has been discussed in this study. Materials and Methods: The synthesis of novel spiro pyrrolidino oxindoles was performed for the construction of amino acid linked polynuclear heteroaromatics by cycloaddition reaction. This reaction method is one of the most important methods for the construction of spiro pyrrolidino oxindole from the commercially available starting material isatin. Then the synthesized compounds were subjected for evaluation of nitric oxide scavenging and cytotoxic effects against tumor cell lines. Results: All the six synthesized compounds demonstrated promising antioxidant and cytotoxic effects in vitro. Conclusion: Form the present study, it can be concluded that the synthesized compounds are fruitful in terms of their chemical purity, structural novelty, marked biological activities (antioxidant and cytotoxic) in vitro and last of all the lucid and picturesque synthetic methodology to synthesize the molecules in a in a non-hazardous and environmental friendly way.

In Vitro Metabolic Stability and Permeability of Gymnemagenin and Its In Vivo Pharmacokinetic Correlation in Rats - A Pilot Study

Gymnema sylvestre is traditionally used for diabetes mellitus. A literature survey revealed very few reports, particularly on rat liver microsomal stability, caco-2 permeability and efflux concerns and its correlation with the bioavailability of gymnemagenin, an important component of G. sylvestre. Therefore, the objective of our study was to investigate the in vitro rat liver microsomal stability and caco-2 permeability along with the efflux of gymnemagenin and establish a probable correlation of these in vitro findings with pharmacokinetic parameters after oral and intravenous administration in rats.Rat liver microsomal stability studies to estimate the in vitro intrinsic half-life, clearance, and Caco-2 permeability after 21 days of culture to determine the apparent permeability from apical to basal and from basal to apical, and efflux ratio of gymnemagenin were performed using liquid chromatography-tandem mass spectrometry. A sensitive, robust bioanalytical method was validated and successfully applied to determine the plasma exposure of gymnemagenin. In vitro rat liver microsomal stability demonstrated that gymnemagenin metabolizes rapidly with a short apparent and intrinsic half-life (~ 7 min) and high intrinsic clearance, i.e., 190.08 µL/min/mg of microsomes. The results of the Caco-2 study indicated a poor permeability (1.31 × 10(- 6 )cm/sec) with a very high efflux ratio. The pharmacokinetic study revealed poor oral bioavailability (~ 14 %) of gymnemagenin and it was found to have a short half-life and a high clearance in rats. Our in vitro findings indicated low metabolic stability and poor Caco-2 permeability with high efflux, which might have a role in the observed poor oral bioavailability in rats.

In vitro antioxidant activities of root extract of Asparagus racemosus Linn.

Objective The purpose of the study is to investigate potential of antioxidant property of ethanolic root extract of Asparagus racemosus Linn (EEAR). Methods In vitro evaluation antioxidant property of EEAR was done using various methods like DPPH scavenging activity, hydroxyl radical scavenging activity, and nitric oxide scavenging activity. HPTLC fingerprint analysis was performed for qualitative determination of possible number of components from the ethanolic extract. Acute toxicity study was performed in Wistar rat and an OECD guideline 423 was followed. Results The yield value was found 0.96% from EEAR. A concentration of 468.57 ± 3.002 μg/ml of probable antioxidant material from EEAR was required to scavenge 50% of DPPH. The IC50 value of EEAR were found to be 508.17 ± 7.37 μg and 416.57 ± 5.08 μg when determined by hydroxyl radical and nitric oxide scavenging assay respectively. The reducing powers of EEAR was 0.295 ± 0.0037 at 125 μg/ml and increased to 0.934 ± 0.0005 at 500 μg/ml. HPTLC fingerprint data supports several basic informations like isolation, purification, quality evaluation and standardization. No sign of toxicity was observed after treated with 2000 mg/kg of EEAR. Conclusion The obtained data highlight the potential role of EEAR as a source of natural antioxidants.

Beverage-induced enhanced bioavailability of carbamazepine and its consequent effect on antiepileptic activity and toxicity

The present study was undertaken to investigate the food-drug interaction of carbamazepine (CBZ). Common fruit juices [grapefruit juice (GFJ), lime juice (LJ)], known to inhibit the enzyme cytochrome P450 3A4 (CYP3A4), and some widely consumed beverages [milk (M), black tea (BT)] were involved in this study in the presence of CBZ, as might happen during clinical therapy. The effects of the beverages on the pharmacokinetics and drug-induced toxicity of CBZ was observed after concomitant administration for a period of 28 days. Accordingly, the influence of altered bioavailability of CBZ on its antiepileptic activity was investigated. A significant shift in the Cmax as well as Tmax of CBZ was observed in the presence of LJ and GFJ. This increase in bioavailability significantly enhanced hepatotoxicity and delayed the onset of tremor and piloerection against pentylene tetrazole (PTZ)-induced seizure in experimental animals. However, increased toxicity of CBZ was found to be absent with BT. Thus, from our observation, LJ or GFJ in the presence of CBZ significantly increased the bioavailability of CBZ, which might lead to increased toxicity and antiepileptic activity of the drug.

Microcredit and Women’s Agency: A Comparative Perspective across Socioreligious Communities in West Bengal, India

Abstract The article explores the impact of a government-sponsored microcredit program in India on women’s decision-making powers across different socioreligious communities (SRCs). The article shows that women’s participation in the Swarnajayanti Gram Swarojgar Yojona (SGSY) has resulted in varied patterns of decision-making across SRCs in four areas chosen for inquiry: (a) money management, (b) food items, (c) use of borrowed money, and (d) kinship and family matters. The likelihood of decisions being taken by “female-only” increased among households participating in SGSY, irrespective of caste and creed, compared to those not participating in it (the control group). However, men continue to take decisions in money management in both the participating and nonparticipating households. In the other three spheres, women of participating households have a greater say as compared to those in the control group

In Vitro and In Vivo Correlation of Colon-Targeted Compression-Coated Tablets

This study was performed to assess and correlate in vitro drug release with in vivo absorption of prednisolone (PDL) from a colon-targeted tablet prepared by compression coating of core tablet. In vivo drug absorption study was conducted using a high performance liquid chromatographic (HPLC) method, which was developed and validated for the estimation of PDL in rabbit plasma. The calibration curve showed linearity in the concentration range of 0.05 to 50 μg/mL with the correlation coefficient (r) of 0.999. The method was specific and sensitive with the limit of detection (LOD) and lower limit of quantification (LLOQ) of 31.89 ± 1.10 ng/mL and 96.63 ± 3.32 ng/mL, respectively. The extraction recovery (ER) of PDL from three different levels of quality control (QC) samples ranged from 98.18% to 103.54%. In vitro drug release study revealed that less than 10% drug was released in 6.34 h and almost complete (98.64%) drug release was achieved in the following 6 h. In vivo drug absorption study demonstrated lower values of C max, AUCtotal, and protracted T max from compression-coated tablet. The results confirmed the maximum release of drug in the colon while minimizing release in the upper gastrointestinal tract (GIT). An excellent in vitro and in vivo correlation (IVIVC) was also achieved after considering the lag time.

Choice Between Microfinance System Operating on the Basis of Individual Liability Loan Contract or Through Joint Liability Loan Contract

In this paper we consider that a representative of a not so affluent rural household has three options. He (she) may join in a microfinance system operating on the basis of individual liability credit contract, or on the basis of joint liability loan contract through forming self-help group or may not participate in any type of microfinance system. This paper establishes that wealthier among the not so affluent rural household prefers to join microfinance system operating on the basis of individual liability loan contract, comparatively less wealthy prefers to join microfinance system operating on the basis of joint liability loan contract and ultra poor is less likely to join any type of microfinance system. This paper establishes that a household with high dependency ratio and higher intra-household decision making power of the head of the women of that household also influences the household to join microfinance system and in both the situations the probability of joining microfinance system operating on the basis of joint liability loan contract is slightly higher. It is also established that microfinance system fails to solve the ageing problem in rural areas because aged persons are less prone to join in any type of microfinance system.

Lipid-drug conjugates: a potential nanocarrier system for oral drug delivery applications

AbstractHydrophilic drugs are preferred candidates for most routes of drug administration, because of their enhanced solubility and dissolution under aqueous in vivo conditions. However, their hydrophilic nature also leads to decreased permeability across hydrophobic barriers. This is a severe limitation in situations where membrane permeability is the primary factor affecting bioavailability and efficacy of the drug. Highly impermeable cellular membranes or the tight endothelial junctions governing the blood-brain barrier are prime examples of this limitation. In other cases, decreased permeability across mucosal or epithelial membranes may require increased doses, which is an inefficient and potentially dangerous workaround. Covalent conjugation of hydrophilic drugs to hydrophobic moieties like short-chain lipids is a promising strategy for maintaining the critical balance between drug solubility and permeability. This article practically focuses on the production procedure of Lipid drug conjugates (LDCs), various formulation methodologies for preparing LDC nanoparticles with detailed about their in vitro physicochemical characterization at laboratory scale. Moreover, brief overviews on the role of LDCs in novel drug delivery applications as a substrate to various disease therapies are provided. Graphical AbstractThree dimensional (3-D) schematic representation of LDCs structures.

Traditional Institutions and Female Beneficiaries of Mahatma Gandhi National Rural Employment Guarantee in West Bengal

Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) ensures 100 days of employment in a year in unskilled manual labor intensive public work at statutory minimum wage for any adult from a household living in rural areas. One important feature is uniform wage across gender. Participation of women gets priority in the program. As per this act, women should constitute at least one-third of the total beneficiaries of the program. In Indian social fabric, women of scheduled caste (SC) community are least restrained by social norms compared to women of upper caste (UC) community and Muslim community. In general, the return from participation in MGNREGA will be highest for those women whose mobility and social interaction is least impeded by conservative social norms. Women hindered most by restrictive social norms may fetch maximum benefits from an intervention if that intervention expands knowledge base or challenges traditional norms of gender. It may be interpreted as non-monotonic effect of restrictedness across caste and religion. Using primary data from three districts of West Bengal, this chapter has tried to see whether there exists any non-monotonic effect of restrictedness on household’s ‘expenditure on consumption,’ ‘expenditure on temptation good,’ ‘expenditure on women’s health,’ and ‘expenditure on children’s education and health’ across social groups. In our study, we have chosen those UC women in the sample who are especially responsive to MGNREGA. If social restrictedness creates bottlenecks for knowledge, and participation of women in MGNREGA allowed UC women to challenge existing gender norms to enhance their agency, then why Muslim women, who most fettered by social norms, did not respond more to MGNREGA than SC women did. One explanation of our result is non-monotonic effect of social restrictions. Participation in MGNREGA has enhanced agency of those women whose agency was constrained due to restrictive social norms, but women subject to severe domination has too little agency to fulfill their goal.