Design, development and evaluation of controlled release multiple unit pellets for potential delivery of antiulcerants

AIM AND OBJECTIVES: The main aim of the present study was to formulate and evaluate enteric coated, controlled release multiple unit pellets of Esomprazole magnesium and Rabeprazole sodium using natural and synthetic polymers. OBJECTIVES: 1. To formulate Esomeprazole magnesium and Rabeprazole Sodium Controlled release Multiple Unit Pellets using various concentrations of Hydroxy Propyl Methyl Cellulose K15, Hydroxy Propyl Methyl Cellulose K100, Ethyl Cellulose, and Xanthan gum by Extrusion Spheronization process. 2. To evaluate the pre - compression parameters like drug excipient interaction study, bulk density, tapped density, compressibility index and angle of repose. 3. To evaluate various post compression evaluation parameters like friability, drug content and in vitro dissolution studies and Scanning Electron Microscopy (SEM) study. 4. To formulate gastric protection for the prepared multiple unit pellets using Hydroxy Propyl Methyl Cellulose Phthalate as enteric polymer. 6. To determine the mechanism and kinetics of drug release. 7. To conduct stability studies on optimized formulation as per ICH guidelines. SUMMARY: In the modern era of Pharmaceutical research much attention has been focussed on patient’s health in terms of therapeutic efficacy and safety. Modified Dosage Form (MRDF) has always been more effective therapeutic alternative to conventional or immediate release. The term modified release drug product is used to describe product that alter the timing and /or the rate of release of the drug substances. There are two types of MRDF .i) Delayed release ii) Extended release. The terms Controlled release (CR), Sustained release (SR) Prolong release (PR) has been used synonymously with extended release dosage forms. Controlled release drug delivery is one which delivers the drug at a predetermined rate for locally (or) systemically for a specified period of time. Controlled release drug delivery system aim to maintain plasma concentration of drugs within the therapeutic window for a longer period of time. Delayed release products are formulated with acid resistance (or) enteric coating protects acid labile drug substance from the gastric environment (or) to prevent adverse events such as irritation. A peptic ulcer is an open sore on the lining of the stomach or duodenum. Gastric and duodenal ulcer is produced by an imbalance between mucosal defences particularly gastric acid and pepsin. In addition, H.pylori infection is a major factor in the pathogenic of peptic ulcer. Proton pump inhibitors (PPI) rank among the top 10 prescribed classes of drugs and are commonly used to treat acid reflux, indigestion and peptic ulcers. PPIs are among the most widely sold drugs in the world and the first one in antiulcer medicine is omeprazole(WHO model list of essential medicines). Among seven available PPI drugs Esomeprazole magnesium and Rabeprazole sodium are classical examples of proton pump inhibitors and are approved by FDA for the treatment of GERD, Peptic ulcer and maintains of erosive esophagites. These drugs will degrading in acidic environment of stomach and will lead to therapeutic in efficacy so it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage forms by using different enteric polymers. The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body to achieve promptly and then maintain the desired drug concentration. Many marketed Esomeprazole and Rabeprazole tablets/pellets are available as enteric coated formulation only. The main aim of the present study was to develop and evaluate enteric coated, controlled release tablets of Esomeprazole magnesium and Rabeprazole sodium using natural and synthetic polymers gives better and more uniform drug absorption and greater bioavailability. To design the multiple unit pellets, we have developed two different spheroid unit of uniform drug content with varying in polymer concentration to achieve rate controlled drug release as per our specification. The first group spheroid unit which contain only drug with spheroidizing polymers was prepared to achieve the minimum effective concentration. The second group of spheroid unit was prepared by using the controlled release polymers HPMC K100, HPMC K15, Ethyl cellulose and Xanthan gum. Among the four polymers HPMC K100 the drug Polymer ratio 1:1.5 shows good controlled release characters in Esomeprazole magnesium and HPMC K 15 the drug and polymer ratio 1:2 shows good controlled release profile in Rabeprazole sodium. The MUPS were prepared by Extrusion -Spheronization a promising pelletization technique. In this process the pellets were prepared by mixing the drug with excipient along with binder solution the resultant mass was extruded through extruder followed by spheronizer and finally dried. The possible interactions between drugs and distinct polymers were investigated via FT-IR Studies. Results proved that Rabeprazole sodium and Esomeprazole magnesium was found to be compatible with excipient as no disappearance of the peaks or shift of the peaks indicating that the drugs are compatible with ingredients. The micromeritics evaluation like Bulk density, Tapped density, Angle of repose, Carr’s index and Hauser’s ratio of the prepared pellets shows good flow property. The post formulation parameters like friability, drug content were carried out and found to be within acceptable limit. SEM study shows the surface morphology of the optimized formulations E2 and R6 the pellets was compact, continuous and was porous in nature, demonstrated the spherical nature of the pellets. Based on in vitro dissolution profile the enteric coated, controlled release multiple unit pellets of Esomeprazole magnesium and Rabeprazole sodium was developed using HPMCK100 in the ratio 1:1.5 ( drug :polymer) and HPMC K15 in the ratio 1:1.5 ( drug :polymer) respectively as controlled release polymer and Hypromellose phthalate HP55 as enteric coated polymer. The optimized formulations E2 (Esomeprazole) and R6 (Rabeprazole) had better resistant to 0.1N HCl and better cumulative percent drug release as compared to other formulation. After 12 hours E2 shows 97.88% and R6 shows 97.59 % cumulative percent drug release as compared to other formulation. So E2 (Esomeprazole) R6 (Rabeprazole) was selected as optimized formulation from the trail batches. The in vivo pharmacokinetic plasma concentration and time curve parameters shows that less plasma concentration fluctuation, lower Cmax, prolonged tmax and MRT of formulated MUPS than that of marketed enteric coated formulations. Stability study revealed there was no significant change in in vitro release profile. All the parameters were within limit after 90 days. CONCLUSION: From the above research finding it can be concluded that controlled release of Esomeprazole Magnesium and Rabeprazole Sodium Multiple Unit Pellets could be developed by using HPMC K100 the drug Polymer ratio 1:1.5 and HPMC K 15 the drug and polymer ratio 1:2 prepared by Extrusion -Spheronization to achieve better bioavailability and extended drug release. Further, the first group spheroid unit could maintain the minimum effective concentration and the second group spheroid unit could release the medicament in control release manner. Hence the prepared Multiple Unit Pellets could achieve both enteric coating and controlled release approach for the potential delivery of Antiulcerants

Phytoplankton Diversity in Relation to Physico-Chemical Parameters of Gnanaprekasam Temple Pond of Chidambaram in Tamilnadu, India

Twelve physico-chemical parameters, diversity and abundance of phytoplankton of fresh water pond of Chidambaram have been studied during September 2007 and August 2008. A total of 14 phytoplankton genera, 4 belonging to cyanophyceae, 4 to chlorophyceae, 3 to Bacilariophyceae and 3 to Euglenophyceae were recorded. To know to the variations in Periodicity and distribution of phytoplankton, various physico-chemical and biological parameters of the pond water have been observed. The values of TDS, BOD phosphate and nitrate and the current status of phytoplankton population imply that the study pond are mesotrophic in nature

Role of serum magnesium levels in febrile seizures: A case control study from a paediatric referral centre in South India

Background: Febrile seizures is one of the most common seizures in children .The exact aetiology of febrile seizures is still not fully understood, serum trace element like magnesium may plays an important role by its direct action on central nervous system. Objective: The aim of my study is to estimate the serum magnesium level and determine its correlation with the occurrence of febrile seizures. Methods: This case control study was conducted on 100 children diagnosed with febrile seizures as the cases and 100 age matched febrile children as the control group. Serum levels of magnesium were measured. Statistical analysis was performed with SPSS software using student-T test. Results: The mean serum magnesium levels were 2.04 mg/dl and 1.98mg/dl in children with febrile convulsion, febrile children without convulsion respectively. There were no significant differences between the cases and controls in term of age and gender. There was no significant difference on serum magnesium between the simple and complex febrile seizures. Conclusion: The serum magnesium levels were found to be normal in cases and controls. This study concludes that there was no significant relationship between serum magnesium level and febrile seizures

A QTAIM approach on poly tetrahydrothiophene molecular wire

The present investigation of structural, charge density and electrical characteristics of Au and thiol substituted poly tetrahydrothiophene molecular wire by using quantum chemical calculations has been carried out with density functional theory (DFT). The various applied electric field (0.00 – 0.26 VÅ-1) altered the geometrical parameters and the corresponding electrostatic and transport properties of the molecule has been analyzed. Interstingly, the applied electric field is increased from 0 eV, the Au−S bond distance at the right terminal is faintly longer than the left end; this variation is resulted from the gold atom at the left end which practices stronger electric field when compared with at the right end of TET molecule. The variations in the atomic charges (MPA, NPA) of the molecule for the various applied electric fields have been compared. The HOMO-LUMO gap of the molecule for zero bias is 1.96eV, as the field increases this gap decrease to 1.31 eV. The ESP shows the potential difference between charges accumulated of the molecule for various applied electric field. The applied electric field polarizes the DCC molecule; as a result the dipole moment of the molecule rises from 2.47 to 15.33 D

Identification and characterization of popular rice (Oryza sativa L.) varieties through chemical tests

Identification and characterization of crop varieties are crucial for ensuring the genetic purity of seeds. The present investigation was carried out to identify suitable chemical methods that are fast, reliable and easy for seed analysts, breeders and seed producers for identification of a variety. Twenty-five popular rice varieties in the seed supply chain of Tamil Nadu were subjected to phenol, modified phenol, NaOH, aroma, gelatinization temperature (alkali spreading value), GA3 and 2,4-D tests. The results of the experiment revealed that phenol and modified phenol tests changed the colour of TKM 9 and TRY 1 variety to brown but no colour change was observed in the variety I.W. Ponni variety. The NaOH test is useful for the identification of TKM 9 variety as it changed the colourless solution to red. GA3 and 2,4-D tests characterized the varieties based on the shoot growth into two and three groups respectively. However, all the variety lacked aroma and exhibited a high gelatinization temperature

Empirical and Numerical Analysis of Aerodynamic Drag on a Typical SUV Car Model at Different Locations of Vortex Generator

The aerodynamic characteristics are concerned with the fuel consumption rate and the stability of a high speed vehicle. The current research aims at studying the aerodynamic behavior of a typical SUV vehicle model mounted with the vortex generator (VG) at various linear positions with reference to its rear roof edge. The flow field around the vehicle model was observed at different wind speed conditions. It had been determined that at the instance of lower wind speed, the VG had minimal effects of aerodynamic drag on the vehicle body. However, at the instance of higher wind speed conditions the magnitude of the drag force decreased significantly. Vehicles move at higher speeds in the highways, location of the VG varied towards the upstream of the vehicle due to early flow separation. Therefore test were conducted at different wind speeds and locations of VG. The numerical simulation conduced in this study provides flow characteristics around the vehicle model for different wind speeds. The realizable k−ε model was used to simulate and validate the empirical results in an effective manner. By using experimental data, the drag was reduced by 9.04 % at the optimized VG location. The results revealed that the induced aerodynamic drag would determine the best car shape. This paper provides a better understanding of VG positioning for enhanced flow separation control

Bar 1-Visibility Drawings of 1-Planar Graphs

A bar 1-visibility drawing of a graph $G$ is a drawing of $G$ where each vertex is drawn as a horizontal line segment called a bar, each edge is drawn as a vertical line segment where the vertical line segment representing an edge must connect the horizontal line segments representing the end vertices and a vertical line segment corresponding to an edge intersects at most one bar which is not an end point of the edge. A graph $G$ is bar 1-visible if $G$ has a bar 1-visibility drawing. A graph $G$ is 1-planar if $G$ has a drawing in a 2-dimensional plane such that an edge crosses at most one other edge. In this paper we give linear-time algorithms to find bar 1-visibility drawings of diagonal grid graphs and maximal outer 1-planar graphs. We also show that recursive quadrangle 1-planar graphs and pseudo double wheel 1-planar graphs are bar 1-visible graphs.Comment: 15 pages, 9 figure

Commuting Accidents among Health Care Workers Working in Malaysia Government Hospitals

Commuting accidents are accidents occurring while travelling to and from work, and in the course of work. Studies have demonstrated that long working hours are associated with deprived sleeping time. Acute sleep deprivation may result in significant changes in cognitive functioning, alteration of mental status resembling depression or anxiety and difficulty with short-term memory. Some other studies have found that sleep deprivation significantly affects physician performance, alertness and patient safety. However, individual factors concerning workers’ behavior, family-related factors (parenting responsibility), work burden, workplace support as well as environmental factors such as bad weather and bad road conditions are also significant contributors of commuting accidents. The aim of this study is to investigate the relationship of long working hours or odd working hours and the risk exposure of the drivers during their work-commuting trips. The study was based on data collected from official notification forms. Sample size for this research was 554 based on 2014 to 2017 reported cases. Review of the statistics showed that most of the commuting accident causalitiesoccurred during travel to work (30.1%), compared to back from work after normal office hours (28.7%) and during odd hours (night shift and post-call) (12.5%). Nurses contributed significantly to these causalities (53%), followed by hospital attendants (17%), medical officer and assistant medical officer, respectively, 6 percent. Theincreasing number of commuting accidents among healthcare workers is alarming. As such, it is timely that proactive actions be taken by employers to educate their employees, their most valuable assets, on safe commuting management. Keywords: commuting accident, healthcare workers, road crashe

Prevalence of Sickness Absence and Its Sociodemographic and Occupational Factors in a Public Service Organization

Sickness absence in any particular organization has negative impacts mainly toward economic, morale and productivity. The purpose of this survey is to determine the prevalence of sickness absence among employees in a government office in a central region of Malaysia to get profiling of the employees taking medical leaves, tocompare the frequency of sickness absence among the employees based on gender, age group and designation and to determine the perception of sickness absence among the employees in relation to their occupation. A cross-sectional study was carried out among 587 workers in the first half of 2017. Data was collected based on Sickness Absence Surveillance form, which was filled by any employee who took medical leave. Other variables such as demographic data, work characteristics and personal health were also included. Subsequently, data entry and analysis were done using SPSS Version 22.0. The overall prevalence rate was 63.0 percent (female = 42.6%, male 20.3%) that includes repeated medical certificate (MC)-taker. Reasons for sickness absence are varied like fever, URTI, pregnancy related, injury, diarrhea, clinic follow-up and many more. Results also showed that sickness absenteeism was higher among female, mainly middle managerial level, presently or previously married, aged from 30 to 39, employed in the organization for over 10 years with no background of chronic medical illness. Therefore, the prevalence of sickness absence among employees in a government office in a central region of Malaysia and factors associated with it are determined. It is recommended for continuation of surveillance simultaneously to have an intervention program in order to find the root cause of sickness absence and thus reducing sickness absence rate. Keywords: sickness absenteeism, surveillance, sociodemographic factors, occupational factor

EFFICACY OF EGG YOLK IMMUNOGLOBULINS (IGY) AGAINST ENTERIC PATHOGENS IN POULTRY*

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