Simultaneous estimation of rosuvastatin and amlodipine in pharmaceutical formulations using stability indicating HPLC method

Utilizou-se abordagem de viabilidade custo-efetividade e isocrática, baseada em CLAE, empregando coluna C-18 (250 mm x 4,6 mm, 5 µm) para separar e avaliar os fármacos, rosuvastatina, anlodipino e seus produtos de degradação induzida por estresse, simultaneamente, em formulações farmacêuticas. Focada nos parâmetros das diretrizes da ICH, a separação eficiente de ambos os fármacos e de seus produtos de degradação foi obtida por meio da otimização da fase móvel com mistura de solventes 30:70 (v/v), respectivamente, acetonitrila e tampão acetato de amônio O,1 M (pH 5). A velocidade de fluxo da fase móvel foi de 1,5 mL/min e todas as detecções foram realizadas em 240 nm, utilizando detector de UV. O método foi linear no intervalo de concentração de 1-200 µg/mL para a rosuvastatina com coeficiente de determinação 0,996. Para o anlodipino, a linearidade ficou na faixa de 0.5-100 µg/mL, com coeficiente de determinação 0,994. Ambos os fármacos, junto com seus produtos de degradação, foram separados em menos de vinte minutos. Os resultados de precisão intra-dia e inter-dia variaram de 0,72 a 1,81% para a rosuvastatina e de 0,83 a 1,88%, para o anlodipino. Os resultados mostram que este método validado pelo ICH pode ser empregado com sucesso tanto para a rotina quanto para a quantificação simultânea da estabilidade de ambos os ingredientes ativos em formulações farmacêuticas.A viable cost-effective and isocratic approach employing C-18 column (250 mm × 4.6 mm, 5 µm) based HPLC has been utilized to separate and estimate the drugs, rosuvastatin, amlodipine and their stress induced degradation products, simultaneously in pharmaceutical formulations. Focused on ICH guideline parameters, the efficient separation of both drugs and their degradation products was achieved by optimizing a 30:70 (v/v) solvent mixture of acetonitrile and 0.1 M ammonium acetate buffer (pH 5) as mobile phase. The flow rate of the mobile phase was 1.5 mL/min and all the detections were carried out at 240 nm using UV detector. The method was linear in the concentration range of 1-200 µg/mL for rosuvastatin with 0.996 coefficient of determination value. For amlodipine, linearity was in the range of 0.5-100 µg/ml with 0.994 coefficient of determination value. Both the drugs along with their degradation products were separated in less than twenty minutes. The results of within-day and between-day precision were varied from 0.72 to 1.81% for rosuvastatin and 0.83 to 1.88% for amlodipine. The results show that this ICH validated method can be employed successfully for the routine as well as stability quantification of both the active ingredients simultaneously in pharmaceutical formulations

Existence theories and exact solutions of nonlinear PDEs dominated by singularities and time noise

The current research deals with the exact solutions of the nonlinear partial differential equations having two important difficulties, that is, the coefficient singularities and the stochastic function (white noise). There are four major contributions to contemporary research. One is the mathematical analysis where the explicit a priori estimates for the existence of solutions are constructed by Schauder’s fixed point theorem. Secondly, the control of the solution behavior subject to the singular parameter ϵ when ϵ → 0. Thirdly, the impact of noise that is present in the differential equation has been successfully handled in exact solutions. The final contribution is to simulate the exact solutions and explain the plots

Biofortification of Diverse Basmati Rice Cultivars with Iodine, Selenium, and Zinc by Individual and Cocktail Spray of Micronutrients

Given that an effective combined foliar application of iodine (I), selenium (Se), and zinc (Zn) would be farmer friendly, compared to a separate spray of each micronutrient, for the simultaneous biofortification of grain crops, we compared effectiveness of foliar-applied potassium iodate (KIO3, 0.05%), sodium selenate (Na2SeO4, 0.0024%), and zinc sulfate (ZnSO4∙7H2O, 0.5%), separately and in their combination (as cocktail) for the micronutrient biofortification of four Basmati cultivars of rice (Oryza sativa L.). Foliar-applied, each micronutrient or their cocktail did not affect rice grain yield, but grain yield varied significantly among rice cultivars. Irrespective of foliar treatments, the brown rice of cv. Super Basmati and cv. Kisan Basmati had substantially higher concentration of micronutrients than cv. Basmati-515 and cv. Chenab Basmati. With foliar-applied KIO3, alone or in cocktail, the I concentration in brown rice increased from 12 to 186 µg kg−1. The average I concentration in brown rice with foliar-applied KIO3 or cocktail was 126 μg kg−1 in cv. Basmati-515, 160 μg kg−1 in cv. Chenab Basmati, 153 μg kg−1 in cv. Kisan Basmati, and 306 μg kg−1 in cv. Super Basmati. Selenium concentration in brown rice increased from 54 to 760 µg kg−1, with foliar-applied Na2SeO4 individually and in cocktail, respectively. The inherent Zn concentration in rice cultivars ranged between 14 and 19 mg kg−1 and increased by 5–6 mg Zn per kg grains by foliar application of ZnSO4∙7H2O and cocktail. The results also showed the existence of genotypic variation in response to foliar spray of micronutrients and demonstrated that a foliar-applied cocktail of I, Se, and Zn could be an effective strategy for the simultaneous biofortification of rice grains with these micronutrients to address the hidden hunger problem in human population

Stability indicating RP-HPLC method for simultaneous determination of gatifloxacin and dexamethasone in binary combination

In this study, conditions were optimized for development of a simple RP-HPLC method for simultaneous analysis of gatifloxacin and dexamethasone in different matrices like pharmaceuticals, human serum and urine. Good separation of gatifloxacin and dexamethasone from the induced degradation products was accomplished using C8 as stationary phase; 0.02 M phosphate buffer (pH 3.0) and methanol (42:58 v/v) as mobile phase. The concentration was measured with DAD at 270 nm. Linearity was observed in the range of 0.000040-0.000280 mol/L for gatifloxacin (r2≥0.999) and 0.000013-0.000091 mol/L for dexamethasone (r2≥0.999). Both the analyte peaks were completely separated from the peaks of induced degradation products as indicated by the peak purity index (≥0.9999 for both analytes). The optimized method is recommended to be used for concurrent analysis of gatifloxacin and dexamethasone in different matrices

Hydrophilic polymers based sustained release matrix tablets of Ibuprofen: Optimization of formulation using Box-Behnken statistical design

The current study was aimed to formulate sustained release matrix tablets of Ibuprofen; a Propionic acid derivative, and is non-steroidal anti-inflammatory agent (NSAID) with analgesic and antipyretic properties and optimize by using a 3-factor 3-level Box-Behnken statistical design as an optimization tool. Matrix tablets were prepared by direct compression technique using HPMC(X1), NaCMC(X2) and Xanthan Gum(X3) as independent variables and % release at 2hr (Y1), % release at 12hr (Y2) and hardness (Y3) of tablet were selected as dependent variables. Regression analysis was performed on dissolution data and construct polynomial regression models for these response variables. Polynomial models were further validated using ANOVA and results indicate that all the polymers used have significant effect on selected response (p<0.05). Contour plots were drawn to evaluate the effect of polymer combination on selected responses. The results obtained from kinetic modeling indicate that drug release follows the non-fickian diffusion process. Hence Box-Behnken statistical design facilitates the formulation and optimization of Ibuprofen sustained release matrix tablets to achieve better bioavailability. Keywords: Matrix tablets, Sustained release, Ibuprofen, Ant-inflammatory, Box-Behnken statistical desig

Gut Microbiome: A New Organ System in Body

The gut microbiome is comprised of various types of bacteria, fungi, protozoa, and viruses naturally occurring in humans and animals as normal microflora. Gut microorganisms are typically host specific, and their number and type vary according to different host species and environment. Gut microbes contribute directly and/or indirectly to various physiological processes including immune modulation, regulation of various neurotransmitter, and hormones, as well as production of many antioxidants and metabolites. They also play a role as antibiotic, anti-inflammatory, anti-diabetic, and anti-carcinogenic agents. Moreover, the ability of gut microbes to attenuate various systemic diseases like coronary heart disease, irritable bowel syndrome, metabolic diseases like diabetes mellitus, and infectious diseases like diarrhea has recently been reported. Current research findings have enough evidence to suggest that gut microbiome is a new organ system mainly due to the microorganisms’ specific biochemical interaction with their hosts and their systemic integration into the host biology. Investigations into the potential ability of gut microbiome to influence metabolism inside their host via biochemical interaction with antibiotics and other drugs has recently been initiated. This chapter specifically focuses on the importance of gut microorganisms as a new organ system

Detection of Paracetamol as substrate of the gut microbiome

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research