A CONTROLLED RELEASE MICROSPHERE FORMULATION OF AN ANTI-DIABETIC DRUG AND CHARACTERIZATION OF THE MICROSPHERE

Objective: Here the objective of this study was to prepare and characterize sustained release metformin loaded microsphere formulation which was prepared by W1/O/W2 emulsion solvent evaporation technique.Methods: Guar gum and sodium alginate were used as a matrix building material, whereas ethyl cellulose was applied as a coating polymer. Here various formulations were prepared by changing the drug and guar gum ratio, and the subsequent drug entrapment efficiency (DEE) and drug release were compared and evaluated.Results: Scanning Electron Microscopy (SEM) studies revealed spherical particles with a smooth appearance. Fourier-transform infrared spectroscopy (FTIR) showed there was no interaction between the ingredients in the final formulation. X-ray Diffraction (XRD) studies showed the emergence of polymorphic forms in the final formulation. The drug entrapment in the final drug loaded microsphere formulations was varied from 30-66.78%. The drug release studies showed the continuous release of the drug through twelve hours. The optimized formulation (f2) found to release 71.5% of drugs at the end of the 12th hour following zero order release kinetics.Conclusion: The increase in gum concentration in the W1 phase, which enhances viscosity in the W1 phase, resulting in an increase in the drug entrapment up to an optimum level and a decrease in the release rate. So, it can prolong the action. So by using this tool, we can say that metformin loaded microsphere formulation would be a suitable pharmaceutical formulation for the treatment of diabetic patients in modern drug therapy for its prolonged action. Â

Effect of Potent Ethyl Acetate Fraction of Stereospermum suaveolens Extract in Streptozotocin-Induced Diabetic Rats

To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200 mg/kg). Administration of the ethyl acetate fraction at 200 mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine

Formulation Development and Evaluation of Diacerein Loaded Microsphere by Spray Coating (Wurster Method)

Diacerein loaded microspheres were prepared by spray coating(wurster method) using hydroxyl propyl methyl cellulose (HPMC) and ethyl cellulose as release retarding polymer with a view to manufacture sustained release drug delivery. Drug content in the microspheres was determined by HPLC assay followed by drug entrapment efficiency.  Shape and Surface topography of Diacerein loaded microspheres was determined by scanning electron microscopy. Fourier transform infrared spectroscopy (.FT-IR), X-ray diffraction Spectroscopy (XRD), and Differential scanning calorimetry (DSC) studies were done to establish drug polymer and other excipients compatibility and stability. Sustained release action was established by In-vitro release study. The result shows that Diacerein loaded microsphere using hydroxyl propyl methyl cellulose and ethyl cellulose polymer can be a new addition in the field of pain management for the treatment of osteoarthritis.   Keywords: Microsphere, Diacerein, HPMC, Ethyl cellulose, Spray coating

Bioequivalence study of two formulations containing 400 mg dexibuprofen in healthy Indian subjects

Objective: This study presents the results of two-period, two-treatment crossover investigations on 24 healthy Indian male subjects to assess the bioequivalence of two oral formulations containing 400 mg of dexibuprofen (CAS 51146-56-6). An attempt was also made to study the pharmacokinetics of dexibuprofen in the local population of Indian origin.Method: Both of the formulations were administered orally as a single dose separated by a one-week washout period. The concentration of dexibuprofen in plasma was determined by a validated HPLC method with UV detection using carbamazepine as internal standard. The formulations were compared using the parameters area under the plasma concentration-time curve (AUC0-t), area under the plasma concentration-time curve from zero to infinity (AUC0-∞), peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax).Results: The results of this investigation indicated that there were no statistically significant differences between the logarithmically transformed AUC0-∞ and Cmax values of the two preparations. The 90 % confidence interval for the ratio of the logarithmically transformed AUC0-t, AUC0-∞ and Cmax were within the bioequivalence limit of 0.8-1.25 and the relative bioavailability of the test formulation was 99.04 % of that of reference formulationjok?.Conclusion: Thus, these findings clearly indicate that the two formulations are bioequivalent in terms of rate and extent of drug absorption. Both preparations were well tolerated with no adverse reactions observed throughout the study

Prospective observational study on peri-operative usage pattern of analgesics

The present work reports a prospective observational study to determine perioperative usage pattern of analgesics. Both general and regional anaesthesia and also different analgesics which is most effective to manage post operative pain were used. 120 patients were studied randomly as per criteria. Techniques of anaesthesia, pre, peri& post operative vitals and pain scores were noted in selected time interval. Pain score recorded 0-3 as mild, 4-6 as moderate & 7-10 as severe. Of all the analgesics administered in peri & postoperative period, Fentanyl (F) alone & in combination with diclofenac (D) were used maximum in perioperative period. These two groups were compared. In postoperative GA cases, majority patients received paracetamol (P) and tramadol (T) and in regional blocks, Pethidine (PE) Phenergan (PH) combination & tramadol were used. These groups werecompared to evaluate pain perception. Fentanyl alone found to be more effectivein maintaining hemodynamic stability. In fentanyl-diclofenac combination, pulse rate and blood pressure were higher than fentanyl alone. Pain scores were significantly higher in GA compared to regional blocks. In GA patients, fentanyl-paracetamol combination decrease pain significantly compared to fentanyl-tramadol combination. But in regional techniques, pethidine, phenergan and tramadol in combination with perioperative fentanyl shows same result for decreasing pain. Fentanyl is a better analgesics compared to fentanyl+diclofenac combination in perioperative period and in case of postoperative period paracetamol is better effective compared to tramadol HCL in combination with fentany

Inhibition of NO2, PGE2, TNF-α, and iNOS EXpression by Shorea robusta L.: An Ethnomedicine Used for Anti-Inflammatory and Analgesic Activity

This paper is an attempt to evaluate the anti-inflammatory and analgesic activities and the possible mechanism of action of tender leaf extracts of Shorea robusta, traditionally used in ailments related to inflammation. The acetic-acid-induced writhing and tail flick tests were carried out for analgesic activity, while the anti-inflammatory activity was evaluated in carrageenan-and dextran- induced paw edema and cotton-pellet-induced granuloma model. The acetic-acid-induced vascular permeability, erythrocyte membrane stabilization, release of proinflammatory mediators (nitric oxide and prostaglandin E2), and cytokines (tumor necrosis factor-α, and interleukins-1β and -6) from lipopolysaccharide-stimulated human monocytic cell lines were assessed to understand the mechanism of action. The results revealed that both aqueous and methanol extract (400 mg/kg) caused significant reduction of writhing and tail flick, paw edema, granuloma tissue formation (P < 0.01), vascular permeability, and membrane stabilization. Interestingly, the aqueous extract at 40 μg/mL significantly inhibited the production of NO and release of PGE2, TNF-α, IL-1β, and IL-6. Chemically the extract contains flavonoids and triterpenes and toxicity study showed that the extract is safe. Thus, our study validated the scientific rationale of ethnomedicinal use of S. robusta and unveils its mechanism of action. However, chronic toxicological studies with active constituents are needed before its use

Stimulation of Heat Shock Protein 90 Chaperone Function Through Binding of a Novobiocin Analog KU-32

Heat shock protein 90 (Hsp90) is a eukaryotic chaperone responsible for the folding and functional activation of numerous client proteins, many of which are oncoproteins. Thus, Hsp90 inhibition has been intensely pursued, resulting in the development of many potential Hsp90 inhibitors, not all of which are well-characterized. Hsp90 inhibitors not only abrogate its chaperone functions, but also could help us gain insight into the structure-function relationship of this chaperone. Here, using biochemical and cell-based assays along with isothermal titration calorimetry, we investigate KU-32, a derivative of the Hsp90 inhibitor novobiocin (NB), for its ability to modulate Hsp90 chaperone function. Although NB and KU-32 differ only slightly in structure, we found that upon binding, they induce completely opposite conformational changes in Hsp90. We observed that NB and KU-32 both bind to the C-terminal domain of Hsp90, but surprisingly, KU-32 stimulated the chaperone functions of Hsp90 via allosteric modulation of its N-terminal domain, responsible for the chaperone\u27s ATPase activity. and studies indicated that upon KU-32 binding, Hsp90 undergoes global structural changes leading to the formation of a partially closed intermediate that selectively binds ATP and increases ATPase activity. We also report that KU-32 promotes HeLa cell survival and enhances the refolding of an Hsp90 substrate inside the cell. This discovery explains the effectiveness of KU-32 analogs in the management of neuropathies and may facilitate the design of molecules that promote cell survival by enhancing Hsp90 chaperone function and reducing the load of misfolded proteins in cells

Identifying sources, pathways and risk drivers in ecosystems of Japanese Encephalitis in an epidemic-prone north Indian district

Japanese Encephalitis (JE) has caused repeated outbreaks in endemic pockets of India. This study was conducted in Kushinagar, a highly endemic district, to understand the human-animal-ecosystem interactions, and the drivers that influence disease transmission. Utilizing the ecosystems approach, a cross-sectional, descriptive study, employing mixed methods design was employed. Four villages (two with pig-rearing and two without) were randomly selected from a high, a medium and a low burden (based on case counts) block of Kushinagar. Children, pigs and vectors were sampled from these villages. A qualitative arm was incorporated to explain the findings from the quantitative surveys. All human serum samples were screened for JE-specific IgM using MAC ELISA and negative samples for JE RNA by rRT-PCR in peripheral blood mononuclear cells. In pigs, IgG ELISA and rRT-PCR for viral RNA were used. Of the 242 children tested, 24 tested positive by either rRT-PCR or MAC ELISA; in pigs, 38 out of the 51 pigs were positive. Of the known vectors, Culex vishnui was most commonly isolated across all biotopes. Analysis of 15 blood meals revealed human blood in 10 samples. Univariable analysis showed that gender, religion, lack of indoor residual spraying of insecticides in the past year, indoor vector density (all species), and not being vaccinated against JE in children were significantly associated with JE positivity. In multivariate analysis, only male gender remained as a significant risk factor. Based on previous estimates of symptomatic: asymptomatic cases of JE, we estimate that there should have been 618 cases from Kushinagar, although only 139 were reported. Vaccination of children and vector control measures emerged as major control activities; they had very poor coverage in the studied villages. In addition, lack of awareness about the cause of JE, lack of faith in the conventional medical healthcare system and multiple referral levels causing delay in diagnosis and treatment emerged as factors likely to result in adverse clinical outcomes

Assessment of preclinical pharmacokinetics and acute toxicity of pioglitazone and telmisartan combination

The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cholesterol level and cardioprotective efficiency along with its antidiabetic activity. Telmisartan, through activation of PPAR-γ receptor exerts insulin sensitizing property in addition to its primary cardioprotective efficiency. Theoretically, a combination of pioglitazone and telmisartan may be beneficial to effectively control the high blood glucose level and management of coexisting cardiovascular complication in diabetes. The aim of this research was to experimentally evaluate the pharmacokinetic interaction of pioglitazone and telmisartan when are coadministered in rat. Pioglitazone and telmisartan were administered orally as a single dose individually and in combination to the rats. The plasma samples of the pharmacokinetic study were analyzed using a validated LCMS method. The acute toxicity of the combination with a high dose in rats was also evaluated as a part of the determination its safety profile. There was no significant change in pharmacokinetic parameters were resulted due to coadministration of pioglitazone and telmisartan in rat. Absence of major toxicological effect supports the safety of the combination in vivo

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection