Synthesis and characterization of a cysteine xyloglucan conjugate as mucoadhesive polymer

O objetivo deste estudo foi melhorar o potencial mucoadesivo do polímero xiloglicano pela ligação covalente de cisteína como unidade de tiol. O polímero xiloglicano foi quimicamente modificado pela introdução de cloridrato de cisteína como grupo contendo sulfidrila. Prepararam-se diferentes lotes de conjugados cisteína-xiloglicano em pH variando de 2 a 6, avaliando-se a incorporação ótima de tiol, o conteúdo de dissulfeto, o comportamento de inchamento, as propriedades reológicas e mucoadesivas. Os conjugados obtidos foram caracterizados in vitro pela quantificação de grupos tiol, mostrando máxima incorporação na xiloglicana (7.67 ± 0.14 %) em pH 5. O conteúdo de grupos dissulfeto foi máximo (2.83 ± 0.12) em pH 6. O índice de inchamento em % no fim de 4 h foi 83.87 para o xiloglicano e diminuiu para os derivados tiolados. O conteúdo foi mínimo para TH2 (78.26), aumentou pouco até TH5 (83.33) e diminuiu, posteriormente, para TH6 (80.13). Os estudos de mucoadesão revelaram que o conjugado xiloglicano-cisteína aumentou mais que duas vezes comparativamente ao polímero não modificado. A viscosidade do tiômero foi maior do que a do xiloglicano devido à formação das ligações dissulfeto.The aim of this study was to improve the mucoadhesive potential of xyloglucan polymer by the covalent attachment of cysteine as thiol moiety. The parent polymer xyloglucan was chemically modified by introducing sulphydryl bearing compound L-cysteine HCl. Different batches of xyloglucan-cysteine conjugates were prepared at varying reaction pH (2-6) and evaluated for optimum thiol incorporation, disulphide group content, swelling behavior, rheological properties and mucoadhesive properties. The obtained conjugates characterized in vitro by quantification of immobilized thiol groups; showed maximum thiol incorporation on xyloglucan (7.67 ± 0.14 %) at pH 5. The disulphide group content was found maximum (2.83 ± 0.12) at pH 6. The water uptake at end of 4 h was 5.0 for xyloglucan and was found to decrease in thiolated derivatives with increase in thiolation. Mucoadhesion studies revealed that mucoadhesion of xyloglucan-cysteine conjugate increased more than twice compared to the unmodified polymer. The viscosity of thiomer was more than that of xyloglucan because of formation of disulphide bonds

Constraining electroweak and strongly charged long-lived particles with CheckMATE

Long-lived particles have become a new frontier in the exploration of physics beyond the Standard Model. In this paper, we present the implementation of four types of long-lived particle searches, viz. displaced leptons, disappearing track, displaced vertex (together with muons or with missing energy), and heavy charged tracks. These four categories cover the signatures of a large range of physics models. We illustrate their potential for exclusion and discuss their mutual overlaps in mass-lifetime space for two simple phenomenological models involving either a U(1)-charged or a coloured scalar.Comment: 28 pages, 7 figures; minor typesetting changes and references adde

Search for long-lived particles decaying to a pair of muons in proton-proton collisions at s=13\sqrt s = 13 TeV.

An inclusive search for long-lived exotic particles decaying into a pair of muons is presented. The experimental signature is a pair of oppositely charged muons originating in a common secondary vertex displaced from the proton-proton collision point by distances ranging from several hundred micrometers to several meters. The search is conducted using data collected in 2016 and 2018 by the CMS experiment at the LHC in proton-proton collisions with a center of mass energy $\sqrt{s} = 13$ TeV in 2016 and 2018, corresponding to an integrated luminosity of 97.6 fb$^{-1}$. The results are interpreted in the framework of the Hidden Abelian Higgs Model, and a simplified model in which Long Lived Particles are produced in the decay of an exotic heavy neutral scalar boson

SOLUBILITY ENHANCEMENT OF GLIBENCLAMIDE USING MESOPOROUS SILICA

Glibenclamide is a BCS Class II drug and poses a major problem during formulation development. In the present study, adsorption onto various carriers was used to enhance the solubility of glibenclamide. It was observed that solubility of glibenclamide was greatly enhanced by adsorbing onto mesoporous silica. The increase in solubility of poorly soluble drugs is often associated with the generation of supersaturation, which results in the risk of drug precipitation. HPMC E5 was used as precipitation inhibitor to maintain sink condition for a longer duration. A 32 full factorial design was adopted to optimize the ratio of glibenclamide (X1) and mesoporous silica as a carrier (X2) and the effect of different ratios was studied on percent yield, percent drug loading, and percent drug release. X-ray powder diffraction (XRPD) and Differential scanning calorimetry studies were performed to investigate any possible interaction in between glibenclamide and mesoporous silica. An optimum batch of drug adsorbate was used to prepare immediate-release tablets. The tablets prepared were evaluated for thickness, uniformity of weight, hardness, friability, in-vitro disintegration time, and in vitro drug release study

ANALYSIS OF MECHANISMS FOR TOLERATING MULTIPLE LINK FAILURES IN MPLS NETWORK

Multiprotocol Label Switching (MPLS) is switching network and provides significant benefits by fast forwarding packets. MPLS is scalable network and it is useful for end-to-end quality of service (QoS), it also enabling efficient utilization of existing network resources. In MPLS, there is no admission control for nodes and it is connection-oriented network which makes network more reliable. For MPLS network, failure can be occur at any point of time if the network link is overloading with traffic or node leave network. If the link failure occur in the MPLS network then there is need to establish a new label switched path (LSP) and then forward the packets to the newly established LSP. The forwarding of failed link traffic to different or backup path this may leads LSP get more congested. Here some mechanisms used for to tolerate these link failures in MPLS network. The main focus to analyze the various mechanisms used for tolerates the link failure in MPLS based on the Quality of Service (QoS) parameters. The expected result from this thesis, the network should maintain connectivity after multiple failures without causing congestion

Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance

Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC–MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium

Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance

Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC–MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium