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In the current investigation, white mustard mucilage from whole seeds of Sinapis alba was evaluated for its physical properties and compared with the other mucoadhesive polymers such as hydroxy propyl methylcellulose 5Cps and Carbopol 934P. Further, methanol precipitable solids from whole leaves of Aloe Vera L were used as permeation enhancer. To achieve improved bioavailability of diltiazem, novel buccal adhesive tablets (NBATs) in cup and core fashion designed to achieve unidirectional release towards mucosa were prepared in a three-stage process using specially fabricated punches. The adhesive cups were studied for its shear, tensile, and peel strengths by specially designed apparatus using excised ruminant and porcine buccal mucosa as model substrates. Ex vivo permeation studies in a Franz diffusion cell were conducted through porcine buccal mucosa. Fourier transform infrared spectroscopy studies and differential scanning calorimetry thermographs showed no remarkable interactions. Histopathological studies showed no remarkable damage of buccal mucosa by the NBATs. In vivo studies were conducted on anaesthetized male New Zealand albino rabbits, estimated by reversed-phase high-performance liquid chromatography, and the pharmacokinetics were compared with the oral and intravenous bolus injection. NBATs exhibited a Cmax 74.6 ng/mL, Tmax 3.5 h, t(1/2) 4.36 h. The NBATs prevented salivary scavenging effect and exhibited 82.1% bioavailability.

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Novel mucoadhesive buccal tablets (NMBT) of oxytocin were prepared as core in cup fashion to release the drug unidirectionally towards the buccal mucosa. Adhesive cups were prepared with a mucilage isolated from edible Dillenia indica fruits (DIM). Shear, tensile and peel strengths of prepared adhesive cups were estimated on freshly excised bovine buccal mucosa. Core tablets were formulated with oxytocin using permeation enhancers viz. sodium taurocholate and sodium thioglycollate. In vitro permeability studies of NMBT were conducted in a Franz diffusion cell containing 50 mL of phosphate buffer pH 6.6 at 37 +/- 0.2 degrees C through excised bovine buccal mucosa. In vivo studies on anaesthetized New Zealand albino male rabbits were conducted and drug levels in plasma were estimated at 220 nm by reverse phase HPLC using BDS Hypersil C8 column using acetonitrile and 0.05 M potassium dihydrogen orthophosphate buffer pH 6.6 (20:80 v/v) as mobile phase, at a flow rate of 1.25 mL/ min. Optimized formulation showed C(max), T(max), t1/2 and AUC(total), 688 pg/mL, 2 h, 0.079 h, and 1999.72 h x pg/mL respectively. The NMBT containing 0.75% w/w sodium taurocholate showed 27% bioavailability without damaging the buccal mucosasuggesting its suitability as an alternative to noninvasive administration of oxytocin.

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Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to optimize the rate of drug dissolution and permeation. A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug and excipients. Advances in experimental and computational methodologies will be helpful in shortening the processing time from formulation design to clinical use. This paper aims to review the developments in the buccal adhesive drug delivery systems to provide basic principles to the young scientists, which will be useful to circumvent the difficulties associated with the formulation design.

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We report here studies on the effect of high pressure on the structural properties of nano-sized Europium sesquioxide (Eu2O3) up to a pressure of about 16.4 GPa. At ambient conditions, the starting sample was found to be predominantly cubic type Eu2O3 or in Eu3+ state with a trace of Eu2+. The presence of Eu2+ state is assumed to be arising due to the non-stoichiometric Eu(1-x)O phase which is obtained from XPS studies by the deconvolution of the Eu 3d-core levels. The Raman studies at ambient show a strong peak at about 333 cm(-1), which is known to occur due to the Fg mode of cubic Eu2O3 and in a similar way, the XRD data shows major peaks corresponding to the cubic phase of Eu2O3. A Mao-Bell type diamond anvil cell (DAC) was used to generate high pressures for XRD and Raman spectroscopy studies. It was observed that the material undergoes a structural change from cubic to monoclinic structure with an on set transition pressure at around 2 GPa and completes at around 8 GPa. This has been inferred from the fact that above about 2.0 GPa pressure, Raman studies show the emergence of a new peak corresponding to the monoclinic phase which increases in intensity and shifts further with increase in pressure, while the XRD studies show that above about 2.0 GPa, the peaks corresponding to monoclinic phase emerge, which show a slight increase in preferred orientation as the pressure is increased. A detailed discussion has been provided to explain this fact.

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Ferroelectric materials such as lithium niobate and lithium tantalate show a non-linear hysteresis behaviour, which may be explained by dynamical system analysis. The behaviour of these ferroelectrics is usually explained by domains and domain wall movements. So, the spatial variation of the domain wall was studied previously in order to see its effect on the domain wall width in the context of the Landau-Ginzburg functional. In the present work, both temporal and spatial variations of polarization are considered, and by using the Euler-Lagrange dynamical equation of motion, a Klein-Gordon equation is derived by taking the ferroelectrics as a Hamiltonian system. An interaction has been considered between the nearest neighbour domains, which are stacked sideways in a parallel array with uniform polarization. This interaction term is associated with the spatial term and when this interaction is assumed to be zero, the spatial term vanishes, giving rise to a Duffing oscillator differential equation, which can be also studied by a dynamic system analysis.

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Chloroquine-resistant Plasmodium vivax malaria was first reported in India in 1995. This report led to the round-the-year monitoring, in Calcutta (West Bengal) and Mayurbhanj district (northern Orissa), of the in-vivo sensitivity of local P. vivax to chloroquine (CQ). Between January 1998 and December 2001, 800 cases with microscopically confirmed P. vivax malaria were enrolled in the study. Each was given CQ in the regimen recommended both by the Government of India and the World Health Organization (i.e. a total of 25 mg/kg, over 3 days). Only six cases, of the 480 who completed the scheduled 28 days of follow-up, failed to clear their parasitaemias by day 5. Even these six cases had only low-level parasitaemias on day 5, and all were aparasitaemic by day 7. In the study area, despite the wide-spread abuse of CQ and the increasingly frequent reports of CQ-resistant P. falciparum, CQ appears to remain an effective drug in the treatment of P. vivax.

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The ferredoxin of the extreme haloarchaeon Halobacterium salinarum requires high (>2 M) concentration of salt for its stability. We have used a variety of spectroscopic probes for identifying the structural elements which necessitate the presence of high salt for its stability. Titration of either the fluorescence intensity of the tryptophan residues or the circular dichroism (CD) at 217 nm with salt has identified a structural form at low (<0.1 M) concentration of salt. This structural form (L) exhibits increased solvent exposure of W side chain(s) and decreased level of secondary structure compared to the native (N) protein at high concentrations of salt. The L-form, however, contains significantly higher levels of both secondary and tertiary structures compared to the form (U) found in highly denaturing conditions such as 8 M urea. The structural integrity of the L-form was highly pH dependent while that of N- or U-form was not. The pH dependence of either fluorescence intensity or CD of the L-form showed the presence of two apparent pK values: approximately 5 and approximately 10. The structural integrity of the L-form at low (<5) pH was very similar to that of the N-form. However, titration with denaturants showed that the low pH L-form is significantly less stable than the N-form. The increased destabilization of the L-form with the increase in pH was interpreted to be due to mutual Coulombic repulsion of carboxylate side chains (pK approximately 6) and due to the disruption of salt bridge(s) between ionized carboxylates and protonated amino groups (pK approximately 10). Estimation of solvent accessibility of W residues by fluorescence quenching, and measurement of decay kinetics of fluorescence intensity and anisotropy strongly support the above model. Polylysine interacted stoichiometrically with the L-form of ferredoxin resulting in nativelike structure. In conclusion, our studies show that high concentration of salt stabilizes the haloarchaeal ferredoxin in two ways: (i) neutralization of Coulombic repulsion among carboxyl groups of the acidic residues, and (ii) salting out of hydrophobic residues leading to their burial and stronger interaction.

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Theophylline loaded conventional suppositories, sustained release matrix suppositories and sustained release two layered suppositories were prepared using polyethylene glycol 4000 and eudragit RS-100 and their characteristics were evaluated both in-vitro and in-vivo. In comparison to conventional suppositories, the release of the drug from sustained release matrix suppositories was gradual and extended over a period of time. On the other hand two layered suppositories produced an initial quick release followed by extended release of the drug. The in-vivo results were found to correlate with the in-vitro results.

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Ferredoxin from the haloarchaeon Halobacterium salinarum is a 14. 6-kDa protein with a [Fe2-S2] center and is involved in the oxidative decarboxylation of 2-oxoacids. It possesses a high molar excess of acidic amino acid residues and is stable at high salt concentration. We have purified the protein from this extreme haloarchaeon and investigated its salt-dependent stability by circular dichroism, fluorescence, and absorption techniques. The predominantly beta-sheeted protein is stable in salt concentrations of >/=1.5 M NaCl. At lower concentrations a time-dependent increase in fluorescence intensity ratio (I(360):I(330)), a decrease in the absorption at 420 nm, and a decrease in ellipticity values are observed. The rate of fluorescence intensity change at any low salt concentration is the highest, followed by absorption and ellipticity. This suggests that at low salt the unfolding of ferredoxin starts with the loss of tertiary structure, which leads to the disruption of the [Fe2-S2] center, resulting in the loss of secondary structural elements.

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Ethylcellulose microcapsules containing theophylline were prepared by the phase-separation coacervation process induced by non-solvent addition in the presence of variable amounts of polyisobutylene. No statistical difference was evident between the different sized microcapsules with respect to their drug content, wall thickness and in-vitro drug dissolution profiles. Poly-isobutylene was, however, found to influence the release profiles of drug to a great extent. An increase in polyisoburylene concentration retarded the release of theophylline from the microcapsules due to the formation of smaller and spheroidal coacervate droplets in larger volumes, which resulted in the formation of more evenly coated microcapsules. Although the release of theophylline from the microcapsules was found to fit both the first order and diffusion controlled release processes, differential rate treatment indicated that the overall release, in fact, was governed by diffusion controlled process.

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A study was undertaken to elucidate the life cycle of the parasite A.oraoni, isolated from man. For the purpose, operculated eggs were isolated from faeces of oraon tribals belonging to the village Bandipore, district North 24-Parganas of West Bengal province of India. The purified eggs were incubated at different temperatures, salinity and pH. Larvae (miracidia) could be observed to develop between the 7th and 8th day of incubation at a temperature range between 22 degrees-30 degrees C. While the optimum pH was observed to be neutral, larval development did not take place at salinity beyond 0.8 per cent. To identify the correct intermediate host, all available species of snails from the study village were colonised and infected with the laboratory hatched miracidia from human derived operculated eggs. It was observed that of all the snails infected, only Lymnaea supported the development of rediae from miracidia, which could be observed on the 32nd post infection day. Considering the results of the experimental study, it was hypothesised that Lymnaea spp. of snails under natural condition also, might act as the first intermediate host for A. oraoni.

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In an attempt to establish the diarrhoeogenic potential of the newly identified Artyfechinostomum oraoni, which was associated with human diarrhoea in a tribal community near Calcutta, India, two naturally infected domestic pigs of the locality were followed in captivity. Both pigs developed fatal diarrhoea after 5 months. The autopsy revealed a massive infection with the echinostome on a haemorrhagic and oedematous mucosa of the jejunum and duodenum extending up to pyloric end of the stomach. It is suggested that similar pathology might also be operating in the infected man.

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Role of fatty acid binding proteins (FABPs) in modulating inhibition of human placental malate dehydrogenase by palmitoyl-CoA and oleate has been studied. Activity of human placental cytosolic malate dehydrogenase is detected throughout the gestation, showing a peak at midgestation (20-25 weeks). Inhibition (50%) of the enzyme activity is obtained by 20 microM palmitoyl-CoA or 35 microM oleate. FABPs enhance the activity of malate dehydrogenase in absence of palmitoyl-CoA or oleate and also protect against palmitoyl-CoA or oleate inhibition. Such a modulatory effect of FABP may be due to the binding of long chain fatty acyl-CoA or fatty acid rather than a direct effect of FABPs on the enzyme.

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We found two kinds of benzonitrilases, designated benzonitrilases A and B, in a cell extract of Arthrobacter sp. strain J-1 grown on benzonitrile as a sole carbon and nitrogen source. Benzonitrilases A and B were purified approximately 409-fold and 38-fold, respectively. Purified benzonitrilase A appeared to be homogeneous according to the criteria of polyacrylamide gel electrophoresis. Both the enzymes hydrolyzed benzonitrile to benzoic acid and ammonia without forming benzamide as an intermediate. The molecular weights of benzonitrilases A and B were found to be 30,000 and 23,000, respectively. The subunit molecular weight of benzonitrilase A was the same as its molecular weight. The isoelectric points of benzonitrilases A and B were 4.95 and 4.80, respectively. The optimum temperature and pH, respectively, for benzonitrilase A were 40 degrees C and 8.5, and those for benzonitrilase B were 30 degrees C and 7.5. The K(m) values for benzonitrilases A and B were 6.7 mM and 4.5 mM, respectively. Both the enzymes degraded p-tolunitrile, 4-cyanopyridine, and p-chlorobenzonitrile, but they did not attack aliphatic nitriles or amides. Both the enzymes were inhibited by thiol reagents.

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Tumours induced in Balb/c mice by Abelson virus complex were found to contain a xenotropic virus (A-X-MuLV) and an NB-tropic, dual-tropic virus (NBX), in addition to the Moloney leukaemia virus (M-MuLV) and the defective, transforming Abelson virus genome. Both A-X-MuLV and NBX virus were presumably present in a genomically masked form and could be recovered only by co-cultivation of tumour cells with permissive cells. Only about 0.87% and 0.13% of the viruses in the co-culture supernatant represented A-X-MuLV and NBX virus respectively; the majority were M-MuLV. The NBX virus acted more efficiently than the HIX virus (Fischinger et al., 1975) as helper to rescue murine sarcoma virus (MSV) from S+L-cells of hamster, rat and mouse origin, whereas the converse was true for those of cat and human origin. The interference and nuetralization patterns suggested that the NBX virus was an env gene recombinant between A-X-MuLV and M-MuLV. The fact that NBX virus cross-reacted in radioimmunoassays with gp70s of both M-MuLV and Balb: virus-2 provides evidence for the recombinant nature of the NBX gp 70-coding gene which was probably derived from both M-MuLV and a virus similar to Balb: virus-2 or A-X-MuLV. The presence of a unique antigenic determinant on the gp70 of NBX virus is also suggested. Both A-X-MuLV and NBX virus cross-reacted with type-specific p12s of M-MuLV and Balb: virus 2- suggesting that the gag gene coding for p12 of NBX virus was derived from the A-X-MuLV, which was itself a recombinant, its p12-coding gene being derived from both Balb: virus-2-like virus and M-MuLV. The NBX virus was not oncogenic when tested in newborn Balb/c mice.

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