Department of Pharmacy

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    Strateic Plan for Effective Health Services
    (2012) Shailendra, Priyadarshi
    Strategic Planning for health Services is a subject of intensive and extensive newlineinvestigations by academicians as well as management professionals Different models newlineand measures have been developed during the last few years and a large number of newlineorganizations have used them in different situations and contexts The thesis tries to newlineassess and evaluate these models and measures to capture the different perceptions and newlineperspectives of Health services Strategic management so as to provide a significant newlinelearning for researchers and professional managers a better understanding newlineA raging debate is always there as to how important and big the role of Strategic Planning newlineis there for effective management of health services We propose that strategic newlinemanagement or planning has a very big role in helping SSBHS to be successful in the newlinerole it has been envisaged to play on the borders We further propose that if Strategic newlinePlanning SP is developed early at the entry level in SSBHS the health professionals and newlinethe health services can effectively meet the challenges and societal requirements on the newlineborders Thus they might also contribute to human capital formation This thesis aims at newlinestudying the applications of Strategic Management in health services for SSB and newlinebeneficiaries outside the ambit of SSB found from literature and a few studies available newlinerelating to the application of Strategic management in health services besides findings of newlinethe feedback received from the Purposive Quota Sampling method applied for collecting newlinedata newlineThis study will be helpful in providing feedback about the potential and limitations of newlineeach individual to SSBHS and other stakeholders inside and outside the ambit of SSB newlineThough the primary attention of the strategic plan is excellence in health care newlinedispensation there is simply too much evidence that SSB and other Central Paramilitary newlineForces CPF should not and cannot neglect the development of Training and newlineInfrastructure for Health Services newlineEmerging trends necessitate new studies and applied research.
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    Pharmacokinetics and Biodistribution Studies of Selected Racemic Drugs
    (BITS Pilani, 2013) Dubey, Sunil Kumar
    Regulatory considerations and aspect of chirality started in the early 1990s Regulatory agencies require clinical efficacy and safety data of each enantiomeric form before giving approval Latest data reveal that 75percentage of drugs approved after the year 2000 are pure enantiomers It is well known that asymmetry plays an important role in most of the biological processes As the physiological environment is chiral therefore enantiomeric molecules are expected to differ in their pharmacokinetic profile and pharmacological behavior However to study such separation of enantiomers is very important Chiral separation of enantiomers helps in understanding the pharmacological profiles of racemates and enantiomers There is an increase in the demand of chiral separation methods in industries as racemates are being replaced by single enantiomeric forms The method development for enantiomeric separation is challenging and time consuming Chiral separation and analysis enhances the clarity of the pharmacological and toxicological data obtained and can also help in controlling the quality of synthesized drugs This thesis deals with the enantiomeric separation and stereospecific disposition of two important pharmaceutical drugs with respect to their pharmacokinetics and biodistribution The first drug ketorolac is a nonselective COX inhibitor in the family of heterocyclic acetic acid derivatives Ketorolac is an isostere of ketoprofen The second drug chosen was venlafaxine which is an antidepressant of SNRI category Both drugs are available as racemates and are important and widely used The objective of the present study was to understand the pharmacokinetics and biodistribution behavior of above drugs after developing simple reliable rapid and sensitive analytical and bioanalytical methods As venlafaxine is converted to Odesmethylvenlafaxine in system therefore it is also studied along with venlafaxine.
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    Synthesis and Structure Activity Relationship of New Aryl and Heteroaryl Semicarbazones as Anticonvulsants
    (BITS Pilani, 2006) Shalini
    In the present thesis, six series of aryl and heteroaryl semicarbazones and their analogues were designed and synthesized based on 3-dimenstional four point pharmacophore model using both CHARMM (ACD 3D views) and MM3 (Alchemy 2000) force fields. The structure of the synthesized compounds was confirmed by spectral (IR, 1H-NMR, Mass) and elemental analysis. The synthesized compounds were preliminary evaluated for their anticonvulsant activity by MES and scPTZ tests. Compounds which showed promising activity, were further tested in scPTZ and scPIC screens. The synthesized compounds were also evaluated for various CNS side effects i.e. neurotoxicity, depression and behavioral despair effect. Neurochemical study has also been done on some selective compounds to discover the mechanism behind their anticonvulsant activity. The synthesized compounds were tested for their effect on the GABA level in the rat brain tissues/whole brains. Quantum mechanical modeling and structure activity relationship studies were also carried out on these compounds to understand the structural features essential for activity. The effect of EHOMO, ELUMO and and#916;E on anticonvulsant activity was studied. The higher the and#916;E values, greater was the activity profile. Along with this HOMO surface analysis was also done, to confirm the pharmacophoric requirement for anticonvulsant activity. Most of the synthesized compounds exhibited broad spectrum of activity i.e. exhibited protection in more than one seizure model. The most potent compound with broad spectrum of activity was found to be compound TR-18 (4-(4-fluorophenyl)-5-(4-hydroxyphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one), which exhibited protection in all the four seizure models with lesser neurotoxicity and behavioral side effects. The compound resulted in a 10-fold increase in the GABA level in rat brain when compared to the control.
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    Design Synthesis and Pharmacological Evaluation of Novel Phosphodiesterase FourInhibitors for their Anti Depressant and Anxiolytic Potential
    (BITS Pilani, 2015) Muthu Venkatesh Sudali
    Phosphodiesterase-4(PDE4), an important component of the cyclic adenosine monophosphate (cAMP) cascade, selectively metabolizes cAMP in the brain to theinactive monophosphate. Their inhibitors may offer novel strategies in the treatment of depression. However, its development as antidepressant drugs has been encumbered by their side effects profile of non-selective PDE inhibitors like nausea, emesis,gastrointestinal side-effects, and vascular toxicity. These side-effects can be minimized by specifically targeting isozymes in the particular tissue or the cell of interest. So, we were interested in developing novel, PDE4 inhibitors with better isozyme selectivity and further explore their potential as anti-depressant and anxiolytics.The novel pharmacophoric requirements derived from nitraquazone and its related compounds as potential PDE4 inhibitors that include key elements: a) a planar scaffold providing a HBA and b) two hydrophobic substituent s with their corresponding linker(1 and 2). On the basis of the proposed pharmacophore, six different series of N4 newlinesubstituted quinoxaline based carboxamides with variations on linker-1 and/or newlineunsubstituted/substituted hydrophobe, and while two series of N3 substituted quinazoline newlinebased carboxamides which are positional isomer of quinoxaline-carboxamides were newlinedesigned as per the pharmacophoric requirements as novel PDE4 inhibitors. newlineThe first series comprises of linker-1 having alkyl group and unsubstituted hydrophobe newlinei.e., benzyl (QCA), while in second series substituted hydrophobe having strong newlineactivating group (OCH3) at para-position i.e., 4-methoxybenzyl (QCB), and in third series newlinesubstituted hydrophobe having strong deactivating group (CN) at para-position i.e., newline4-cyanobenzyl (QCC) were designed and synthesized. Similarly unsubstituted newlinehydrophobe with linker-1 having carbonyl group viz., benzoyl (QCD), or having both alkyl newlineand carbonyl group i.e., 2-phenylacetyl (QCE), or (n = 2) increased alkyl chain length i.e., newlinephenethyl (QCF), while two series of N3 substituted
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    Synthesis and Pharmacological Evaluation of Novel Heterocyclic Compounds as Potential Agents for the Treatment of Schizophrenia
    (BITS Pilani, 2008) Chandra Sekhar, K.V.G.
    In the present study, three series of compounds viz., I: 2-{4-[4-(substituted thiazolyl)phenylethyl] piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles (NC : 1-7), II: 4-{4-[2-(4-(2-substituted quinoxalin-3-yl) piperazin-1-yl)ethyl]phenyl} thiazoles (QCC : 1-7; QCMO : 1-7; QCMH : 1-7), IIIa: N-{2-[4-(substituted)piperazin-1-yl]-2-oxo ethyl} acetamide (P : 1-7) and IIIb: N-2-{4-[4-(2-substitutedthiazol-4-yl)piperazin-1-yl]-2-oxo ethyl} acetamide (AG:1-7) were designed in accordance with the strategy promulgated by Ariens targetting Schizophrenia. The designed compounds were synthesized by conventional method and wherever possible, reactions were carried out using microwave irradiation technique under solvent free conditions. The newly synthesized compounds were charaterized by spectral data (IR, 1H NMR and MS) and elemental analysis. The synthesized compounds were evaluated for their 5-HT2A and D2 receptor antagonistic activites in in vivo pharmacological models using Cage Climbing Assay and Quipazine induced head twitches respectively in Swiss albino mice. NCEs were also tested for catalepsy in Swiss albino mice. In series I, the compound NC6 was found to be the most active one with 5-HT2A/ D2 ratio of 1.1143 and an average cataleptic score of zero. In series II, the compound QCMH4 was found to be the most active one with 5-HT2A/ D2 ratio of 1.23 and an average cataleptic score of zero. In series IIIa, the compound P4 was found to be the most active one with 5-HT2A/ D2 ratio of 0.853 and an average cataleptic score of zero. In series IIIb compound AG3 was found to be the most active compound with 5-HT2A/ D2 ratio of 1.128 and an average cataleptic score of zero. Some of the compounds of Series I and series II were also evaluated for their receptor binding affinity at 5-HT2A and D2 receptors using radio ligand binding assays. In series I, NC6 was found to be the most active with Ki of 6.33 and#956;M towards the D2 receptor and 11.2 and#956;M towards the 5-HT2A receptor.
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    Evaluation of topical formulations of selective cyclooxygenase 2 cox 2 inhibitiors for analgesic and antiinflammatory efficacy as well as plasma concentration profile
    (BITS Pilani, 2009) Shirumalla Raj Kumar
    Selective cyclo-oxygenase-2 (COX-2) inhibitors have been in use as analgesic and anti-inflammatory agents for over a decade. In addition they have been shown to have beneficial effect in cancer chemotherapy. However, COX-2 inhibition has been associated with an increased risk of cardiovascular as well as other adverse events in several clinical trials. Delivery of coxibs by topical route can be useful to avoid the adverse drug effects, without losing the beneficial effects of the coxibs. Topical formulations of Rofecoxib and Celecoxib were prepared, evaluated for its acceptability, efficacy and safety. These were tested for physical appearance, pH, spreadability, drug content uniformity and in vitro diffusion. Emulsion gel formulations were prepared containing 1-3% Rofecoxib or 3-5% Celecoxib (w/w) along with optimized amounts of Carbopol 940, Labrasol and Ethanol. Use of sub-micronised Rofecoxib/ Celecoxib in the above formulation (FG14/ FG30, respectively) resulted in improved in vivo efficacy. Selected formulations FGI4 and FG30 were evaluated in models of acute and chronic inflammation as well as hyperalgesia. Comparison of systemic exposure following topical as well as oral dosing by determining plasma concentrations of Rofecoxib/ Celecoxib in test animals, determination of skin irritation, gastic ulceration or other systemic adverse effect potential after chronic exposure and determining of ex-vivo COX-1 and COX-2 inhibition potential in rat blood were conducted to study the safety of topical gels. 1% (w/w) Rofecoxib gel, FG14 and Celecoxib gel containing 5% (w/w) of the drug, FG30, was significantly (p < 0.05) more effective in inhibiting inflammation and hyperalgesia associated with inflammation, compared to placebo gel, in acute and chronic model.
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    Studies on the Drug Resistance Genes in Plasmodium falciparum and Plasmodium vivax from India
    (BITS Pilani, 2008) GARG, SHILPI
    Malaria remains the world s most devastating human parasitic infection, afflicting more than 500 million people and causing about 1.7 million to 2.5 million deaths each year. Efforts to combat malaria have received a major setback due to the development of parasite resistance to the various drug regimens used. Due to increased resistance, a regular monitoring in the field is required for effective malaria control strategies. Molecular probes that reliably predict susceptibility of P. falciparum or P. vivax to various drugs like Chloroquine and Sulfadoxine - Pyrimethamine can provide information supporting rational policy decisions and practice with regard to malaria treatment. newline newlineThis study is focused on Bikaner, situated in the North western part of Rajasthan, India, near Indo Pak border. This region is characterized by unstable episodes of P. falciparum and P.vivax malaria after every rainy season with both species showing severe manifestations. To predict the profile of the drug resistance patterns in the parasite population of Bikaner, we analyzed the point mutations in genes responsible for Chloroquine (Pfcrt and Pfmdr-1) and Sulfadoxine Pyrimethamine (dhps and dhfr respectively) resistance. The PfCRT showed the mutant 76T for almost all the samples, while the Pfmdr-1 showed the wild type 86N in more than half of the isolates, indicating a rise in Chloroquine resistance in this region. In contrast, a different resistance pattern was seen in case of Sulfadoxine Pyrimethamine. The DHFR in P. falciparum was predominantly double mutant but in P.vivax the wild genotype was more predominant. In contrast, for both P. falciparum and P.vivax, the DHPS showed the wild genotype for most of the samples. A number of novel mutations were found in DHPS of both P. falciparum and P.vivax. While the novel mutations in PfDHPS showed reduction in binding affinity of Sulfadoxine to the DHPS enzyme, no effect on drug binding was seen for mutated PvDHPS.
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