TRANSBUCCAL DELIVERY OF SPRAY DRIED LOVASTATIN FROM MUCOADHESIVE BUCCAL PATCHES AND IN VITRO CHARACTERIZATION

Objective: The aim of the present work was to develop and characterize mucoadhesive film of spray dried Lovastatin (LVS) for buccal delivery to enhance bioavailability. Methods: Mucoadhesive films were prepared by solvent casting technique by using different polymers HPMCK4M, HPMC E5LV and chitosan. The successful patches were evaluated for film thickness, weight, content uniformity, surface pH, swelling index, folding endurance, ex-vivo residence time, ex-vivo bioadhesion test, in vitro drug release, ex-vivo drug permeation and stability study. Results: The thickness of all prepared patches ranged from 0.21±0.07 to 1.5±0.39 mm, the weight of the film 89.10±0.6 to 128.57±0.3 mg, drug content 85.47±0.87 to 97.33±0.31%, surface pH 5.6±0.67 to 7.6±0.98, swelling index 23.0±4.1 to 76.5±3.6%, folding endurance 165±1.9 to 350±2.5 respectively. Ex-vivo residence time ranged from 2.2±0.08to 8.2±0.17 h and ex-vivo bioadhesive strength 30±0.64 to 66±0.43 g. The formulations with HPMC E5 shown short period of residence time and shows weak force of adhesion., which might be because of low viscosity of the polymer which resulted into weak adhesion. The percentage drug release and ex-vivo drug permeation was in the following descending order HPMC K4M>HPMC E5LV>chitosan. These results confirm the extension of drug release in case of ionic polymer chitosan. The kinetics data shows that drug release and permeation follows nonfiction diffusion. Accelerated stability data revealed that there is no significant change in drug content, in vitro drug release and ex-vivo permeation. Conclusion: It can be concluded that mucoadhesive buccal patch is a promising dosage form to enhance the drug bioavailability by preventing first-pass metabolism thus providing better therapeutic efficacy

2,4-Dichloro-N-phenethyl­benzene­sulfonamide

In the title compound, C14H13Cl2NO2S, the dihedral angle between the phenyl ring and the benzene ring is 69.94 (9)°. Two short intra­molecular C—H⋯O contacts occur and a weak inter­molecular C—H⋯π inter­action is seen in the crystal

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD

Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

Abstract In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 μM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 μM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents

Investor valuation of the abandonment option: empirical evidence from UK divestitures 1985-1991

This paper looks at divestitures by 144 UK firms listed on the LSE from 1985 to 1991 and investigates whether and how accurately investors price the firm's option to abandon assets in exchange for their exit value. Theory prices this real option as an American style put and the model we test includes the major features of the abandonment option literature: stochastic firm value (the underlying security), stochastic exit value (the strike price), intermediate cash flows and uncertain project life. It also includes random events that can short circuit the optimal timing of the divestiture and trigger abandonment prematurely. The empirical implications are that investors do price the abandonment option but that they price it imperfectly because the exit price is private information. We find that the effects of the timing factor are accurately priced. We also find weak evidence that the probability of forced premature abandonment figures in the option pricing