Formulation of Carbopol Capsules for Sustained Release of Losartan Potassium

Sustained release formulations have been extensively studied for their benefits in improving various physicochemical and pharmacokinetic properties of large number of drugs. The aim of this study was to develop and evaluate sustained release capsules of losartan potassium in order to provide drug release over a long period of time. This allows the drug much time for absorption in gastrointestinal tract (GIT) and hence may increase the bioavailability of the drug. Carbopol 971 P was used as rate controlling polymer for the preparation of capsules. The capsules were evaluated for matrix integrity and drug release using USP type II dissolution apparatus. The sustained release capsules showed excellent matrix integrity and released more than 90% of the drug over a period of 12 hours. The kinetic studies showed that the drug release from the carbopol matrices followed Korsmeyer Peppas release kinetics and hence the mechanism of drug release was a combination of more than one processes i.e. diffusion and erossion. Hydration volume as well as matrix integrity were affected by the change in the amount of the polymer in the capsules. The study suggests that carbopol 971P capsules can be efficiently used to control and extend the release of losartan potassium over a long period. Thus improved absorption and bioavailability can be achieved which requires further studies in animals in future. Keywords: Sustained release, Carbopol, Hydration volume, Capsule

INEQUALITIES PERTAINING TO RATIONAL FUNCTIONS WITH PRESCRIBED POLES

Let $\Re_n$ be the set of all rational functions of the type $r(z) = p(z)/w(z),$ where $p(z)$ is a polynomial of degree at most $n$ and  $w(z) = \prod_{j=1}^{n}(z-a_j)$, $|a_j|>1$ for $1\leq j\leq n$.  In this paper, we set up some results for rational functions with fixed poles and restricted zeros. The obtained results bring forth generalizations and refinements of some known inequalities for rational functions and in turn produce generalizations and refinements of some polynomial inequalities as well

Studies of the silkworm enzyme activity and their correlations with economic variables

The experiment was conducted to analyse the larval performance and economic traits of bivoltine silkworm breeds of silkworm (SK-1, SK-6, SK-22, SK-28, SK-33, CSR4, CSR2, NB4D2, DUN6 and APS4) during spring season. The haemolymph total protein, succinate and gultamate dehydrogenase activities were estimated and their correlation with economic traits were also worked out. The results of the study confirmed that among ten bivoltine silkworm breeds, highest haemolymph SDH activity of 3.47 µmoles/ml/mgprotein/min was recorded in the silkworm breed SK1 and least SDH activity of 1.58 µmoles/ml/mg protein/min was recorded in the breed APS4. The highest peak of succinate dehydrogenase activity of 2.65 µmoles/ml/mg protein/min was observed on 7th day of the 5th instar and lowest peak of succinate dehydrogenase activity of 2.39 µmoles/ml/mg protein/min was observed on 4th day of the 5th instar. GDH activity of 0.46 µmoles/ml/mg protein/min was recorded highest in the silkworm breed SK1 and lowest of 0.15 µmoles/ml/mg protein/min was recorded in silkworm breed APS4. The highest peak of haemolymph GDH of 0.36 µmoles/ml/mg protein/min was recorded on 7th day of 5th instar and lowest peak of 0.26 µmoles/ml/mg protein/min was recorded on 4th day of 5th instar. The correlational studies revealed that haemolymph total protein, SDH and GDH were found to be positively corelated with yield by weight and number (cocoon), weight of mature larvae, shell weight ,cocoon weight, shell ratio percent, silk productivity, rate of pupation, fecundity, raw silk percentage  and length of filament. Thus, the study revealed that silkworm breeds like SK1, SK6, SK22 and SK28 as productive breeds and hence may be used for future breeding programmes for evolution of new robust silkworm breed

The Drug Changing Sensitivity and Resistance Pattern of Different Antibiotics and their Minimum Inhibitory Concentration against Salmonella

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Determination of Antibody Titration between Clinical and Community-Based Patients for O, H, AH and BH Antigens in Salmonella Samples

The aim of the study is to determine the baseline antibody titer of Salmonella bacteria in different positive samples with a view to establishing the significant titer for Widal agglutination test in Kashmir. The Widal test was performed on each serum. The slide agglutination test was first done and then positive samples were further subjected to tube agglutination for quantitative titration. The most commonly utilized diagnostic test for enteric fever is a Widal test, which detects agglutinating antibodies against the O, H, AH and BH antigens of S. typhi. The results of the Widal test showed that out of 413 samples 219 were positive for Antigen O, 165 were positive for Antigen H, 17 were positive for Antigen AH and 12 were positive for Antigen BH. The highest percentage cases were with Antigen-O whereas the lowest percentage was found in Antigen-BH. The difference between clinical and community-based patients have been studied. Keywords: Aetiology, Antigen, Enteric fever, Morbidity, Salmonella typhi, Widal test

Elucidation of etiology of colorectal cancer: A study on silencing of p16 gene by promoter hypermethylation

Colorectal cancer (CRC), commonly known as bowel cancer is the third most common cause of cancer-related deaths in the western world. Colorectal cancer is one of the leading malignancies worldwide. CRC has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The usual treatment is surgery and subsequent chemotherapy and radiotherapy. Cancer development and progression is dictated by series of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others. In colorectal carcinogenesis disturbances different from mutations called an epigenetic regulation are also taken into consideration. The aim of this study was to study the promoter hypermethylation of CpG islands of p16 gene in colorectal cancer patients among the Kashmiri population. The study included 70 surgically obtained colorectal samples among which 50 were obtained from colorectal cancer patients and 20 were histopathologically normal colorectal samples. All the samples were histopathologically confirmed before further processing. DNA was extracted from all the samples and was modified using bisulphite modification kit. Methylation-specific polymerase (MSP) chain reaction was used for analysis of the promoter hypermethylation status of p16 gene. The genetic analysis of the cases and controls by MSP- PCR method, for checking the promoter hypermethylation of CpG islands of p16 gene revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of p16 gene. 66% of the cases showed p16 promoter hypermethylation while as 34% of the cases were nonhypermethylated. The study also revealed that 20% of the normal cases also had promoter hypermethylation of p16 gene and 80% did not showed promoter hypermethylation of p16 gene. The association of promoter hypermethylation with colorectal cancer was evaluated by χ2 (Chi square) test with Odds ratio and was found to be significant. Among 29 male cases and 21 female cases, the association of promoter hypermethylation with colorectal cancer was evaluated using Fisher’s exact test and was found to be significant in both males and females. Occurrence of p16 promoter hypermethylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant. When the frequency of p16 promoter hypermethylation was compared with clinical staging of the disease, p16 promoter hypermethylation was found to be certainly higher in Stage III/IV (83.33%) compared to Stage I/ II (56.25%) but the difference was not statistically significant. Also, the degree of p16 promoter hypermethylation increased with the increasing severity of the lesion but the difference was not again statistically significant. These results clearly suggest that p16 aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in colorectal cancer and is reportedly one of the commonest epigenetic changes in the development of human CRC. It also demonstrates that hypermethylation of p16 gene can be designated as epigenetic biomarker for the screening, diagnosis and prognosis of colorectal cancer. The data gives a clue that p16 gene expression can be readily and fully restored and growth rate of cancer cells decreased by treatment of cancer cells with demethylating agents and DNA methylation inhibitors

OCULAR INSERTS - A NOVEL APPROACH IN OCULAR DRUG DELIVERY

Among the ocular dosage forms, the physiological and anatomical constraints put forth by the eye is a significant challenge to the pharmaceutical scientists and researchers to target drugs to the posterior segment of the eye, prolong their contact time with the ocular surface and sustained release. Hence novel drug delivery strategies and formulations are to be developed and explored which will overcome the ocular constraints and provide better patient compliance. At present, various novel and controlled drug delivery systems are being developed in order to attain better ocular bioavailability, sustained action of ocular drugs as well as good patient compliance. Ocular insert is an example of such delivery system. These are sterile preparations, with a thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into cul-de-sac or conjunctiva sac of the eye. Ocular inserts are an alternative approach to overcome the problems associated with conventional ocular dosage forms like solutions, suspensions, ointments, etc. The article hereunder gives a detailed idea about the classification, mechanism of action, formulation, pros and cons; evaluation and future trends of ocular inserts

Formulation and Evaluation of Sustained release tablets of Venlafaxine HCl

The aim of the present study was to develop a tablet formulation for sustained release of venlafaxine HCl. Control or sustained release formulations have great applications in improving the physicochemical properties and the pharmacokinetic profile of the drugs. Carbopol tablets containing venlafaxine HCl were developed successfully by wet granulation technique. The tablets were evaluated for matrix integrity and drug release in 0.1 N HCl using USP II dissolution apparatus maintained at optimum conditions. The developed tablets were robust and possessed excellent physicochemical properties. The tablets showed great matrix integrity and withstood the hydrodynamic environment of the dissolution medium for > 12 hours. The hydration and swelling behaviour of the tablets was excellent. It was found that the swelling characteristics of the tablets depended on the amount of the polymer used in the tablets as well as the polymer/drug ratio. The tablets provided more than 90% drug release over a period of 12 hours. The drug release data was subjected to kinetic dissolution modelling. It was found that the drug release from the tablets followed Korsmeyer-Peppas model of drug release. This suggests that the mechanism of the drug release from the formulations may be both diffusion as well as polymer erosion. Keywords: Sustained release, Carbopol, Venlafaxine HC

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention