Dyslipidemia and electrolyte metabolism in essential hypertensive North Indians

Background: In the present study we are going to evaluate lipid profile and Electrolytes levels (Sodium, Potassium in Serum & Urine) in Essential Hypertensive and in healthy controls in North Indian Population.Methods: A total of 210 age and sex matched E. hypertensive & healthy controls were included in our study from outpatient department (OPD) of Medicine in King George Medical University, Lucknow, India. First group consist of 110 subjects were known E. hypertensive patients (B.P ≤ 139/89mm of Hg). Another group is control group consist of 100 subjects who were healthy controls (B.P ≤ 120/80mm of Hg) with no history of hypertension. Fasting venous blood sample was collected from all the subjects in plane vacationer and the sample was centrifuged for the estimation of lipid profile & electrolyte i.e. Sodium (N+) & Potassium (K+). Lipid profile was measured with an automated analyzer (Biochem) & Electrolytes was measured using ion-selective electrolyte auto-analyzer in the Clinical lab of biochemistry in KGMU.Results: After analyzing results almost control subjects had normal lipid profile level. In patients of E. hypertension there was a highly significant increase in serum Total Cholesterol (p˂0.0001), LDL-Cholesterol (p˂0.0001) & Triglycerides (p˂0.001). HDL-Cholesterol (p˂0.03) is also significant as compare to controls. Not significant difference was found in serum sodium & potassium level. The Urinary Na+ levels were significantly lower in E. hypertensive patients when compared to controls while Urinary K+ levels were not significant.Conclusion: So we conclude that dyslipidemia is associated with essential hypertension this may due to the genetic predisposition, secondary lifestyles, fatty food consumption, saturated fat, cholesterol in the food increase the blood cholesterol and saturated fat is the main culprit. Essential hypertensive is linked with increased Na+, K+ - ATPase activity and increased renal tubular sodium reabsorption.

Effect of different photoperiods on the growth and survival of juvenile of Indian major carp, Catla catla

The experiment was conducted to determine the effects of different photoperiods and darkness on the growth and survival of juvenile Catla catla in the laboratory for 90 days. Fishes were divided into four aquaria (10 fish per aquarium), and subjected to different photoperiod regimes of 8 hours light:16 hours dark (8L:16D), 16 hours light:8 hours dark (16L:8D), continuous light (24L:0D) and complete darkness (0L:24D). The maximum and minimum growth was observed in the group subjected to continuous photoperiod and complete darkness, respectively. The mean body weight of these groups was significantly different (p<0.05) from other groups which was observed from day 60. Survival rate was 100 percent in all the aquaria subjected to different photoperiods except one which was under continuous dark, where 30 percent mortality was recorded. Mean final growth rate, specific growth rate and daily feed intake were maximum in the group subjected to continuous photoperiod and their means were significantly different (p<0.05) from other groups of fish of different photoperiod regime. A continuous photoperiod is suggested for better growth and survival of rearing juvenile Indian major carp, C. catla under controlled conditions

The solvation and dissociation of 4-benzylaniline hydrochloride in chlorobenzene

A reaction scheme is proposed to account for the liberation of 4-benzylaniline from 4-benzylaniline hydrochloride, using chlorobenzene as a solvent at a temperature of 373 K. Two operational regimes are explored: “closed” reaction conditions correspond to the retention of evolved hydrogen chloride gas within the reaction medium, whereas an “open” system permits gaseous hydrogen chloride to be released from the reaction medium. The solution phase chemistry is analyzed by 1H NMR spectroscopy. Complete liberation of solvated 4-benzylaniline from solid 4-benzylaniline hydrochloride is possible under “open” conditions, with the entropically favored conversion of solvated hydrogen chloride to the gaseous phase thought to be the thermodynamic driver that effectively controls a series of interconnecting equilibria. A kinetic model is proposed to account for the observations of the open system

Clofazimine acid-base solubilization: influence of small organic acids’ concentration

Methods for drug solubilization have become important part of modern drug discovery and development due to increasing number of extremely insoluble drugs and drug candidates. One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2]. We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. The aim of the present study was to investigate CFZ solubilization using the ABS approach. Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids showed some solubilization effect. The effect of their concentration (and the solution pH value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect of CFZ solubilization is much more pronounced when the acid concentration is raised above 2 M. These results can be used as the basis for further CFZ formulation optimization. Furthermore, our ongoing research is focused on the type of interactions and other possible factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solubilization as a general methodology in drug design and development

Clofazimine acid-base solubilization: influence of small organic acids’ concentration

Methods for drug solubilization have become important part of modern drug discovery and development due to increasing number of extremely insoluble drugs and drug candidates. One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2]. We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. The aim of the present study was to investigate CFZ solubilization using the ABS approach. Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids showed some solubilization effect. The effect of their concentration (and the solution pH value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect of CFZ solubilization is much more pronounced when the acid concentration is raised above 2 M. These results can be used as the basis for further CFZ formulation optimization. Furthermore, our ongoing research is focused on the type of interactions and other possible factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solu bilization as a general methodology in drug design and development

Revealing the story of an orphan drug: clofazimine speciation and solubilization as a function of pH

Since the introduction of combinatorial chemistry and high-throughput screening in drug discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo complicated reactions in aqueous solution, such as forming precipitates or complexes with buffer species or undergoing self-aggregation (dimer, trimer, etc.)1,2 or micelle formations. Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, determined by a suitable method. In a pH-dependent measurement of a property (e.g. solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of measured values, but paradoxically, such preference can lead to inaccurate rationalization of the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, the use of calculated pKas can substantially wrench the interpretation of solution properties. Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 40 years, exhibits some of the properties of relatively recent drug molecules by being extremely water insoluble and having variable pKa values reported. We have recently combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to water, the dimer would be more water soluble than the monomeric free base. In saturated solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount importance for understanding of CFZ speciation and the future progress in developing its improved formulations which is the subject of our ongoing studies

Revealing the story of an orphan drug: clofazimine speciation and solubilization as a function of pH

Since the introduction of combinatorial chemistry and high-throughput screening in drug discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo complicated reactions in aqueous solution, such as forming precipitates or complexes with buffer species or undergoing self-aggregation (dimer, trimer, etc.) or micelle formations. Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, determined by a suitable method. In a pH-dependent measurement of a property (e.g. solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of measured values, but paradoxically, such preference can lead to inaccurate rationalization of the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, the use of calculated pKas can substantially wrench the interpretation of solution properties. Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 40 years, exhibits some of the properties of relatively recent drug molecules by being extremely water insoluble and having variable pKa values reported. We have recently combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to water, the dimer would be more water soluble than the monomeric free base. In saturated solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount importance for understanding of CFZ speciation and the future progress in developing its improved formulations which is the subject of our ongoing studies

Dispersion and release of embelin from electrospun biodegradable, polymeric, membranes

In this work, microfiber meshes containing embelin, a poorly water-soluble bioactive agent, were prepared by solubilizing embelin in a biodegradable and biocompatible polymer matrix of poly(ε-caprolactone) (PCL). Plain or drug-loaded, highly porous, fibrous membranes with a high area-to-volume ratio were obtained by electrospinning. Non-woven microfibrous meshes were formed by uniform bead-free fibers with a mean diameter of 1.2 μm. Non-porous films were obtained by solution casting, and were used for comparison. The drug-loading content of the prepared systems was appropriate for topical applications. The thermal properties revealed that the crystallinity of embelin significantly decreased, the drug having almost completely dissolved in the PCL fibers. The in situ bioavailability of embelin, an antimycotic agent, is an important aspect to consider in topical drug applications. The drug-loaded systems presented different contact areas with the biological environment. When comparing the ability to expose embelin with the biological environment of the prepared systems, drug-loaded fibrous scaffolds showed a higher bioavailability of the bioactive agent because of an increase by 86% in the area-to-volume ratio, providing an effective area per unit mass that was 5.8-fold higher than that of the film. For the meshes, 90% embelin release was observed after 12h of exposure to phosphate-buffered saline, whereas for the films a comparable level of release occurred only after 72h.Fil: Cortez Tornello, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Tapia, Alejandro. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Veiga, Itiara G.. Universidade Estadual de Campinas; BrasilFil: Moraes, Ângela M.. Universidade Estadual de Campinas; BrasilFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cuadrado, Teresita Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

Ispitivanje kompatibilnosti nateglinida s pomoćnim tvarima u razvoju tableta nateglinida za trenutno oslobađanje

Experiments were done to assess the compatibility of nateglinide with selected excipients in the development of immediate release tablets of nateglinide by thermal and isothermal stress testing (IST) techniques. To evaluate the drug-excipient compatibility, different techniques such as differential scanning calorimetric (DSC) study, infra-red (IR) spectrophotometric study and isothermal stress testing were adopted. The results of DSC study showed that magnesium stearate exhibited some interaction with nateglinide. However, the results of IR, and IST studies showed that all the excipients used in the formula were compatible with nateglinide. Optimized formulations developed using the compatible excipients were found to be stable over 3 months of accelerated stability studies (40 ± 2 C and 75 ± 5 % RH). Overall, compatibility of excipients with nateglinide was successfully evaluated using a combination of thermal and IST methods and the formulations developed using the compatible excipients were found to be stable.Koristeći termičke metode kao što su diferencijalna pretražna kalorimetrija (DSC) i infra-crvena spektrofotometrija (IR), te izotermička stres-testiranja (IST) ispitana je kompatibilnost nateglinida s izabranim ekscipiensima u razvoju tableta nateglinida za trenutno oslobađanje. Rezultati DSC ispitivanja pokazala su da magnezijev stearat stupa u određenu interakciju s nateglinidom. Međutim, IR i IST ispitivanja pokazuju da su svi upotrijebljeni ekscipiensi kompatibilni s nateglinidom. Optimirana formulacija bila je stabilna preko 3 mjeseca u testovima ubrzanog starenja (40 ± 2 C i 75 ± 5 % RH). Kompatibilnost ekscipiensa s nateglinidom uspješno je evaluirana koristeći kombinaciju termičke i IST metode, a formulacije razvijene koristeći kompatibilne ekscipiense bile su stabilne

Preparation and Evaluation of Poly(Ethylene Glycol)–Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

A series of monomethoxy poly(ethylene glycol)–poly(lactide) (mPEG–PLA) diblock copolymers were designed according to polymer–drug compatibility and synthesized, and mPEG–PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug