Pradipta Kumar Behera

Static and dynamic model for 1-naphthol fluorescence quenching by carbon tetrachloride in dioxane—acetonitrile mixtures

Abstract The quenching of 1-naphthol fluorescence by carbon tetrachloride (CCl 4 ) has been studied in different solvent mixtures of acetonitrile and dioxane at room temperature. The quenching is found to be appreciable and a positive deviation from linearity was observed in the Stern-Volmer plot in all the solvent mixtures even at moderate CCl 4 concentrations (0.1 M or less). This could be explained satisfactorily by a static-dynamic model. The static quenching constant K o values indicate that the ground-state complex is weak and independent of solvent polarity, whereas the dynamic quenching constant K sv depends on the solvent polarity.

Interaction of N-alkyl styryl pyridinium dyes with TX-100 in aqueous medium: Role of the alkyl chain during solubilisation

Abstract Interaction of a series of N -alkyl styryl pyridinium dyes having varied alkyl chain (C n ) with nonionic surfactant (Triton X-100) solution has been studied by using absorption and emission techniques. The binding constants of the dyes (C 1 –C 18 ) with the surfactant aggregates have been calculated and found to increase with increasing alkyl chain length of the dyes. A decrease in the CMC value of TX-100 in presence of the dyes with increasing chain length has been observed and the phenomenon is attributed to the increasing hydrophobicity of the additive. The relative E T (30) values of the local environment of the dyes in TX-100 micelles with respect to standard solvents have been determined. A solubilisation strategy of the micelle for the dyes has been reported where the cationic head group remains in the oxyethylene cage of the micelle and the hydrophobic tail remains buried in the micellar core due to pulling effect.

FTIR and Raman Spectroscopic Investigations of a Norfloxacin/Carbopol934 Polymeric Suspension

Till now very few formulations are available from which the drug is uniformly absorbed, so that the safe and effective blood level of norfloxacin could be maintained for a prolonged period. To fulfill this requirement, a controlled release mucoadhesive suspension was prepared by using a mucoadhesive carbopol934 polymer. The chemical interaction between norfloxacin and the polymer in formulation (prepared by an ultrasonication method) has been studied by FTIR and Raman spectroscopy. From the spectral interpretation, it has been found that in formulation, the carboxylic groups of norfloxacin and hydroxyl groups of carbopol934 undergo chemical interaction, leading to esterification and hydrogen bonding. The formation of micellies due to esterification and hydrogen bonding causes more drug entrapment and a stable formulation. From this it can be concluded that the formulation of norfloxacin may give a better controlled release and mucoadhesive action in the gastrointestinal tract. Hence, carbopol934 could be considered as an effective carrier for norfloxacin.

Photochemistry in microemulsions: fluorescence quenching of 1- and 2-naphthol by Cu2+

Abstract The fluorescence characteristics of 1- and 2-naphthol in the presence of copper ion have been studied in aqueous medium and sodium lauryl sulphate (NaLS)-isobutanol-hexane-water microemulsion. On excitation 1-naphthol (1-ROH) dissociates completely and 2-naphthol (2-ROH) partially in aqueous medium. The dissociation of 2-ROH is suppressed completely and that of 1-ROH partially in the microemulsion. The extent of dissociation of 1-ROH varies with changing microemulsion formulation. The dissociation behaviour and fluorescence quenching of naphthols by Cu 2+ in the microemulsion suggest a compartmentalization of the fluorophores. Various quenching models have been analysed to explain the quenching efficiency. A generalized model explaining both the dynamic and transient quenching processes has been proposed. The probable number of quenchers present in the quenching sphere of action has been calculated.

Photochemistry in microemulsions: Fluorescence quenching of naphthols and their O-alkyl derivatives by CCl4

Abstract The fluorescence characteristics of 1- and 2-naphthols and their O-alkyl derivatives in presence of carbon tetrachloride have been studied in hexane and in sodium lauryl sulphate (NaLS)-isobutanol-hexane-water microemulsions. The fluorescence quenching of the fluorophore by CCl4 obeys the linear Stern-Volmer equation in most of the cases except in oil-in-water microemulsion. A quenching sphere of action model has been proposed for the deviation and the number of quenchers present in the quenching sphere of action has been calculated. The dielectric constant of the water-in-oil and oil-in-water microemulsion surface has been evaluated to be 27.36 and 34.31, respectively.

Photochemistry in microemulsions: fluorescence quenching of naphthols by some γ-picolinium salts

Abstract The fluorescence quenching behaviour of naphthols by some water-soluble quenchers like (methylene), bis-(γ-picolinium bromide) and 1-hexyl y-picolinium bromide have been studied in aqueous medium, and in both water-rich and oil-rich regions of NaLS (sodium lauryl sulfate)-isobutanol-hexane-water and CTAB (cetyltrimethyl ammonium bromide)-isobutanol-hexane-water microemulsion systems. From the fluorescence quenching behaviour, the localization sites of the fluorescent probes in microemulsions have been identified. The charge on the surfactant head group has been found to have significant effect on the quenching phenomena of the naphthols by the pyridinium salts. Both linearity and deviation from linearity in Stern-Volmer plots have been observed during the quenching process and a sphere of action model has been proposed for positive deviation.

Role of different biodegradable polymers on the permeability of ciprofloxacin

Since permeability across biological membranes is a key factor in the absorption and distribution of drugs, drug permeation characteristics of three oral suspensions of ciprofloxacin were designed and compared. The three suspensions of ciprofloxacin were prepared by taking biodegradable polymers such as carbopol 934, carbopol 940, and hydroxypropyl methylcellulose (HPMC). The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and excised goat gastrointestinal membranes in acidic as well as alkaline pH. To know the permeability of drug from control/formulations through different membranes in acidic/alkaline pH, cumulative percentage drug permeation, apparent permeability (Papp), flux, and enhancement ratio (ER) were calculated. Considering Papp and flux values of all formulations, it is evident that formulation containing HPMC was the most beneficial for improving permeation and diffusivity of ciprofloxacin even after 16 h. Hence, this preparation may be considered as the most suitable formulation to obtain prolonged release action of the drug. The ER values of all formulations, through excised goat intestinal mucosal membrane in alkaline pH, were higher than those formulations through goat stomach mucosal membrane in acidic pH. Enhancement ratio values of those formulations indicate that the permeability of the drug was more enhanced by the polymers in the intestinal part, leading to more bioavailability and prolonged action in that portion of the gastrointestinal tract. It may also be concluded from our results that HPMC containing formulation was the best suspension, which may show effective controlled release action. Even carbopol containing formulations might also produce controlled release action.

Effect of different polymers on in vitro and ex vivo permeability of Ofloxacin from its mucoadhesive suspensions

Considering the importance of drug permeation from formulations, in vitro and ex vivo drug permeation characteristics of three oral mucoadhesive suspensions of Ofloxacin were designed and compared. Three suspensions of Ofloxacin were prepared by taking two grades of Carbopol polymer such as Carbopol 934 (C934) and Carbopol 940 (C940); and Hydroxypropyl methylcellulose. The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and excised goat gastrointestinal membranes in acidic as well as alkaline pH. To know the permeability of the drug from control/formulations through different membranes in acidic/alkaline pH, cumulative percentage drug permeation, apparent permeability (Papp) and flux (J) were calculated. In addition, enhancement ratio (ER) of each formulation was also determined. From our results, it is evident that formulation containing C940 was the best suspension considering Papp and J values of all formulations. Moreover, it was the most beneficial formulation for improving permeation and diffusivity of Ofloxacin even after 16 h. Hence, this suspension was probably the most suitable formulation to obtain prolonged release action of the drug. The ER values of all formulations through the excised goat intestinal mucus membrane in alkaline pH were higher than those formulations through the goat stomach mucosal membrane in acidic pH. ER values of those formulations indicate that the permeability of the drug was more enhanced by the polymers in the intestinal part, leading to more bioavailability and prolonged action in that portion of the gastrointestinal tract. It may also be concluded from our results that in addition to formulation containing C940, other formulations may also show effective controlled release action.

Solvent Effect on the Potential Energy Surfaces of the F– + CH3CH2Br Reaction

Although substantial work has been undertaken on reaction pathways involved in base-promoted elimination reactions and bimolecular nucleophilic substitution reaction of F- on CH3CH2X (X = Cl, Br, I), the effect of solvents with varying dielectric constants on the stereochemistry of each of the reaction species involved across the reaction profile have not yet been clearly understood. The present investigation reports the effect of solvents on the potential energy surfaces (PES) and structures of the species appearing in the reaction pathway of F- with bromoethane. The PESs in the gas phase have been computed at MP2 level and CCSD(T) level. The performance of several hybrid density functional, such as B3LYP, M06, M06L, BHandH, X3LYP, M05, M05-2X, and M06-2X have also been investigated toward describing the elimination and nucleophilic substitution reactions. With respect to MAE values and to make the computation cost-effective, we have explored the implicit continuum solvent model, CPCM in solvents like cyclohexane, methanol, acetonitrile, dimethyl sulfoxide and water. The reactant complexes proceed through the subsequent steps to produce fluoroethane as the substitution product and ethylene as one of the elimination products. For elimination reaction both syn and anti elimination have been explored. The calculated relatives energies values, which are negative in the gas phase, are found to be positive in polar solvents since the point charge in the separated reactants are more stabilized than the dispersed charge in the transient complex, which has also been analyzed through NBO analysis.

Raman spectroscopy as a tool for nondestructive qualitative analysis of pharmaceutical formulations

D recent years, a sudden rise in interest for biosimilar molecules by large pharmaceuticals has been evident due to two major factors i.e., larger application of biosimilars strategy to control escalating health-care cost and impending expiration of patents of popular blockbusters. Analytical strategy adopted for these molecules, widely differs from that of small molecules, due to inherent variations in living systems involved during manufacturing process and large size of biomolecules. Considering these facts, regulators have also emphasized multidimensional (structural, cellular potency and similar clinical efficacy) approach for their market approvals.Analytical strategy adopted for qualification and quantitation of P-38 (Mol. Wt. 44 kDa) and mAb (Mol.Wt. 141 kDa) molecules, demonstrate a systematic approach towards such applications. Qualitative analysis included BioConfirm set-up and acquisition of Q1 spectrum for molecules. Mol. Wt. was confirmed through deconvoluted spectrum approach and had a good agreement with theoretical reference. Phosphogluconoylation (for P-38) and glycans presence (for mAb) were manifested in decisions for quantitation strategy.Selection of multiple qualifier ions (m/z 3156.6988 and 2736.0254) for single quantifier ion (m/z 3087.5633) was adopted for establishing linearity from 15 to 300 nanogram for P-38 (top-down approach). To demonstrate bottom-up approach; mAb was digested with LysC enzyme and extracts were analyzed to establish a linearity for range of 1 to 4000 microgram range using four quantifier ions (m/z 495.7553, 481.7634, 321.5115 and 288.1718). Above strategy provides a clear rational approach for discovery researches to begin and implement analytical instrumentation approach towards large biological therapeutics quantitation.B has facilitated the discovery of treatments for some of the most severe diseases known to man – worldwide. Now days in market, patients have access to many biotechnology drugs and vaccines, and medical science is working to grow that number every day. Biologic medicines are made in living organisms to produce proteins to treat various diseases, often by genetically modifying cell constructs or cell lines. When exclusive rights like patents for the first generation of approved biopharmaceuticals got either expired or are about to expire, the market is opening for generic versions, referred to as ‘biosimilars’ (European Union) or ‘follow-on protein products’ (United States). These are also called as similar biological medicines. Some of these are already on the market in Europe. Biosimilar medicine is similar to biological medicine which has already been authorized as the ‘biological reference medicine’. The active ingredients of both biosimilar medicine and biological medicine are similar and are used in general at the same dose to treat the same disease. Since biosimilar and biological reference medicines are similar but not identical, so the name, appearance and packaging of a biosimilar medicine differ to those of the biological reference medicine. A biosimilar manufacturer must commence pre-clinical and clinical studies so as to present pertinent data which establishes the quality, safety and efficacy of the product, as well as its similarity with the reference product. Biosimilars are still new and emerging market. Regulatory guidelines and standards are still being developed in some countries and they are constantly evolving as technology develops.In vivo interaction studies of ACE inhibitor (captopril) was carried out with commonly used NSAIDs (flurbiprofen and ibuprofen) in carrageenan induced inflammation (CII) rats to check the anti-inflammatory response of NSAIDs with captopril and alone. In our study the altered anti-inflammatory response was observe for NSAIDs when given simultaneously with captopril by comparing decrease in paw size (edema). Results were expressed in% reduction in paw size for every hour and were calculated for edema rate and percentage reduction using the formula, Edema rate (E%)=VT – VO/VO * 100 Where, VO=Rat’s hind paw volume before 1% Carrageenan administration and VT=Rat’s hind paw volume at t hour. Percentage reduction (R%)=E C – E T \ E C *100 Where, E C =Edema rate of control group and E T =Edema rate of test compound at t hour. Tukey’s post-hoc test was conducted to determine group means differences taking significant level p<0.05 and p<0.005 highly significant. It has been observed while comparing the anti-inflammatory response of commonly used NSAIDs alone and in combination with captopril that the activity of NSAIDs was enhanced by the addition of captopril as% reduction got higher and edema rate decreased. The synergistic effects of captopril with flurbiprofen and ibuprofen were observed on reduction of inflammation.