Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs

Lyophilized muco-adhesive wafers with optimum drug loading for potential buccal delivery have been developed. A freeze-annealing cycle was used to obtain optimized wafers from aqueous gels containing 2% κ-carrageenan (CAR 911), 4% pluronic acid (F127), 4.4% (w/w) polyethylene glycol with 1.8% (w/w) paracetamol or 0.8% (w/w) ibuprofen. Thermogravimetric analysis showed acceptable water content between 0.9 and 1.5%. Differential scanning calorimetry and X-ray diffraction showed amorphous conversion for both drugs. Texture analysis showed ideal mechanical and mucoadhesion characteristics whilst both drugs remained stable over 6 months and drug dissolution at a salivary pH showed gradual release within 2 h. The results show the potential of CAR 911 and F127 based wafers for buccal mucosa drug delivery

Linear Polarization Features in the Quiet-Sun Photosphere: Structure and Dynamics

We present detailed characteristics of linear polarization features (LPFs) in the quiet-Sun photosphere from high resolution observations obtained with Sunrise/IMaX. We explore differently treated data with various noise levels in linear polarization signals, from which structure and dynamics of the LPFs are studied. Physical properties of the detected LPFs are also obtained from the results of Stokes inversions. The number of LPFs, as well as their sizes and polarization signals, are found to be strongly dependent on the noise level, and on the spatial resolution. While the linear polarization with signal-to-noise ratio $\geq4.5$ covers about 26% of the entire area in the least noisy data in our study (with a noise level of $1.7\times10^{-4}$ in the unit of Stokes $I$ continuum), the detected (spatially resolved) LPFs cover about 10% of the area at any given time, with an occurrence rate on the order of $8\times10^{-3}$ s$^{-1}$ arcsec$^{-2}$. The LPFs were found to be short lived (in the range of $30-300$ s), relatively small structures (radii of $\approx0.1-1.5$ arcsec), highly inclined, posing hG fields, and move with an average horizontal speed of 1.2 km s$^{-1}$. The LPFs were observed (almost) equally on both upflow and downflow regions, with intensity contrast always larger than that of the the average quiet-Sun.Comment: 20 pages, 9 figures, Accepted for publication in the Solar Physics journa

Formulation development of a carrageenan based delivery system for buccal drug delivery using ibuprofen as a model drug

Solvent cast films are used as oral strips with potential to adhere to the mucosal surface, hydrate and deliver drugs across the buccal membrane. The objective of this study was the formulation development of bioadhesive films with optimum drug loading for buccal delivery. Films prepared from κ-carrageenan, poloxamer and polyethylene glycol or glycerol, were loaded with ibuprofen as a model water insoluble drug. The films were characterized using texture analysis (TA), hot stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), x-ray powder diffraction (XRPD), high performance liquid chromatography (HPLC) and in vitro drug dissolution. Optimized films were obtained from aqueous gels containing 2.5% w/w κ-carrageenan 911, 4% w/w poloxamer 407 and polyethylene glycol (PEG) 600 [5.5% w/w (non-drug loaded) and 6.5% w/w (drug loaded)]. A maximum of 0.8% w/w ibuprofen could be incorporated into the gels to obtain films with optimum characteristics. Texture analysis confirmed that optimum film flexibility was achieved from 5.5% w/w and 6.5% (w/w) of PEG 600 for blank films and ibuprofen loaded films respectively. TGA showed residual water content of the films as approximately 5%. DSC revealed a Tg for ibuprofen at −53.87°C, a unified Tm for PEG 600/poloxamer mixture at 32.74°C and the existence of ibuprofen in amorphous form, and confirmed by XRPD. Drug dissolution at a pH simulating that of saliva showed that amorphous ibuprofen was released from the films at a faster rate than the pure crystalline drug. The results show successful design of a carrageenan and poloxamer based drug delivery system with potential for buccal drug delivery and showed the conversion of crystalline ibuprofen to the amorphous form during film formation

Solvent-free electrospinning of liquid polybutadienes and their in-situ photocuring

A single-step approach to rapidly convert low molecular weight polybutadienes into fine rubber crosslinked fibers and nonwoven mats without using any heat or solvent was described. This environmentally friendly method consisted in the electrospinning at room temperature of liquid polybutadiene and polybutadiene-graft-maleic anhydride polymers without any solvent; the flying jet was irradiated to trigger the in-situ curing of the forming fibers at ambient conditions, obtaining a good control over the fibrous morphology and enhancing the performance of the membranes. The kinetics of the photo-crosslinking reaction was studied through FT-IR spectroscopy. Liquid polybutadiene-graft-maleic anhydride polymers demonstrated a faster rate of photocuring, compared to neat polybutadienes. In order to further speed up the reaction, a thiol-based crosslinker and a photoinitiator were introduced into the formulations. The photo-induced crosslinking was more efficient as different reactions concomitantly took place: besides the thiol-ene crosslinking involving the multifunctional thiol crosslinker, the oxidation of the polybutadiene chains and the esterification of the maleic anhydride moieties occurred. Moreover, a polar additive was used to control the electrospinning process by lowering the viscosity and increasing the electrical conductivity. The structural, thermal and surface properties of the fabricated polybutadiene-based electrospun membranes were assessed. The membranes exhibited an excellent morphology stability, high insolubility, good thermal properties and a pronounced hydrophobic character

Development and physico-mechanical characterization of carrageenan and poloxamer-based lyophilized matrix as a potential buccal drug delivery system

Context and objectives: The buccal mucosa presents a unique surface for non-invasive drug delivery and also avoids first-pass metabolism. The objective of this study was the formulation development of polymeric mucoadhesive lyophilized wafers as a matrix for potential buccal drug delivery. Materials and methods: Differential scanning calorimetry (DSC) was used to develop an optimum freeze-cycle, incorporating an annealing step. The wafers were prepared by lyophilization of gels containing three polymers, κ-carrageenan (CAR 911), poloxamer (P407) and polyethylene glycol 600 (PEG 600). The formulations were characterized using texture analysis (for mechanical and mucoadhesion properties), hydration studies, thermogravimetric analysis (TGA), DSC, X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). Results and discussion: DSC showed the eutectic temperature (12.8 °C) of the system where the liquid solution and pure solids both existed at a fixed pressure which helped determine the freeze-annealing cycle at 55 °C for 7 h. Mechanical resistance to compression, hydration and mucoadhesion studies showed that optimized wafers were obtained from aqueous gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600. TGA showed residual water of approximately 1% and SEM showed a porous polymeric network that made ease of hydration possible. Conclusions: Lyophilized wafers by freeze-drying gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600 with optimum physico-mechanical properties has been achieved

Assessment of the rapid shallow breathing index as a predictor of weaning of patients with prolonged mechanical ventilation

Background: About 8 of patients experience prolonged mechanical ventilation after cardiac surgery. Development of criteria for successful liberation of a patient from mechanical ventilation and extubation may be highly dependent on the clinical situation. Different criteria were used for ventilator weaning. We designed a clinical trial to determine the usefulness of rapid shallow breathing index (RSBI) as a predictor for successful weaning from mechanical ventilation. Materials and Methods: In a prospective observational study, 52 patients who had prolonged mechanical ventilation (> 72 h) after open cardiac surgery were studied. Patients had 60 - min spontaneous breathing trials and satisfied at least 5 weaning predictors and fulfilled the criteria for discontinuing mechanical ventilation. Traditional weaning criteria and RSBI were determined. According to the outcome assessment of weaning, patients were divided into failure or success groups. Results: The mean RSBI values were significantly different between the failure (103.5±21.9 breath/min/L) and success groups (80.4±15.3 breath/min/L, p=0.0001). There was no significant difference regarding the values of other prediction criteria between the two groups. Using RSBI <105 (breath/min/L) as the threshold value for predicting successful weaning, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 92.5, 70, 92.5, 70 and 88 respectively. Conclusion: Although a small number of patients require prolonged ventilatory support after open cardiothoracic surgeries, growing experience in critical care settings and mechanical ventilation cause favorable outcomes. Ventilator weaning is more likely to be successful if RSBI is less than 105 (breath/min/L). This index is a more valuable and accurate predictor of weaning than other weaning predictors. © 2007 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran

Design and Experimental Validation of a Cooperative Driving System in the Grand Cooperative Driving Challenge

In this paper, we present the Cooperative Adaptive Cruise Control (CACC) architecture, which was proposed and implemented by the team from Chalmers University of Technology, Göteborg, Sweden, that joined the Grand Cooperative Driving Challenge (GCDC) in 2011. The proposed CACC architecture consists of the following three main components, which are described in detail: 1) communication; 2) sensor fusion; and 3) control. Both simulation and experimental results are provided, demonstrating that the proposed CACC system can drive within a vehicle platoon while minimizing the inter-vehicle spacing within the allowed range of safety distances, tracking a desired speed profile, and attenuating acceleration shockwaves

Formulation, characterisation and stabilisation of buccal films for paediatric drug delivery of omeprazole

This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0–1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation