Geert M. R. Vandenbossche

HOST-REACTION AGAINST EMPTY ALGINATE-POLYLYSINE MICROCAPSULES - INFLUENCE OF PREPARATION PROCEDURE.

Abstract— Microcapsules, prepared with alginate and polylysine, were injected intraperitoneally into mice and the number of peritoneal leucocytes as well as the cells sticking to the capsule wall were counted after 4–28 days. A significant increase in host reaction was observed when the microcapsules contained an outer layer of polylysine as compared with calcium alginate beads without polylysine or microcapsules coated with an outer layer of alginate. The alginate sources influenced the host reaction significantly. After an intraperitoneal residence of 4 days, the microcapsules were mainly surrounded by macrophages. After 28 days, several cell layers surrounded the microcapsules; macrophages, multinucleate giant cells, fibroblasts and mesothelial cells.

Near-Infrared (NIR) Monitoring of H2O2 Vapor Concentration During Vapor Hydrogen Peroxide (VHP) Sterilisation

AbstractPurpose. There is an increasing use in the pharmaceutical industry of barrier systems such as transfer isolators, sterilisation tunnels and work station isolators. As Vapor Hydrogen Peroxide (VHP) sterilisation of isolators and lyophilizers becomes an important sterilisation method, there is an acute need for a VHP monitoring system to be used for in-process control and validation. In this study, near infrared (NIR) spectrofotometry was evaluated as a potential technique to monitor hydrogen peroxide. Additionally the H2O2 vapor permeability of different packaging materials, commonly used in steam and ethylene oxide sterilisation, was evaluated. Methods. NIR spectrofotometry, using a gas cell connected with optic fibres, was evaluated as a potential technique to monitor hydrogen peroxide vapor and water vapor during VHP sterilisation of an isolator. A NIR spectrum was taken every 30 s during VHP sterilisation of an isolator. The influence of injection rate, air flow rate, working temperature and gas distribution was investigated. The H2O2 vapor permeability of different packaging materials was determined by placing the gas cell in the sterilisation bags and sealing the bags hermetically. The sterilisation bag was then subjected to VHP sterilisation. Results. The NIR spectra taken at steady state sterilization conditions showed 4 absorption peaks: at 1364,1378 and 1400 nm attributed to water and at 1420 nm attributed to H2O2 vapor. By measuring the absorbance level at these wavelengths, the actual concentration of H2O and H2O2 vapor in the isolator was calculated. The water vapor permeation of the sterilisation bags, measured with NIR, appeared to be equal for all materials tested. Whereas Tyvek® was the most permeable material for hydrogen peroxide vapor (82.7% of the reference concentration outside the bag), only 30% was found in bags made of medical paper. Sterilisation bags consisting of laminate films and PVC sealed to medical paper showed intermediate permeability. Conclusions. Near-infrared (NIR) spectroscopy using a gascell with optic fibres is a useful technique to monitor VHP sterilisation cycles. There was a difference in H2O2 vapor permeability of different packaging materials, commonly used in steam and ethylene oxide sterilisation.

Host Reaction against Alginate-polylysine Microcapsules Containing Living Cells

Abstract— Syngeneic and nude mice were injected intraperitoneally with saline, empty microcapsules, aggregates of tumourogenic MO4 cells, encapsulated non‐tumourogenic MO cells and encapsulated MO4 cells. The host reaction 4 days after injection, was evaluated by counting the leucocytes in the peritoneal cavity and the cells sticking to recovered microcapsules. A significantly lower number of peritoneal leucocytes was found in mice injected with empty microcapsules or encapsulated MO cells as compared with encapsulated MO4 cells. Histological evaluation showed a significantly higher number of cells sticking to microcapsules containing cells as compared with empty microcapsules. These observations showed that the cellular host reaction against intraperitoneal implants can be evaluated by counting the leucocytes in the peritoneal lavage and histology of recovered capsules.

A fluorescence method for the determination of the molecular weight cut-off of alginate-polylysine microcapsules.

Abstract— Several applications of microcapsules for the encapsulation of living cells or macromolecules require well defined pore sizes. The molecular weight cut‐off of alginate‐polylysine microcapsules has been determined using a range of fluorescent labelled dextran molecules. The diffusion of the fluorescein isothiocyanate labelled (FITC)‐dextrans into the microcapsules was followed by fluorescence and confocal laser scanning microscopy. The permeability of microcapsules for FITC‐dextrans with a molecular weight of 4 700 daltons and the impermeability for FITC‐dextrans with a molecular weight of 40 500 daltons was confirmed with both techniques. Determination of the molecular weight cut‐off, using confocal laser scanning microscopy was more reliable and required a smaller sample than fluorescence measurements.

Influence of the sterilization process on alginate dispersions.

Abstract— The influence of different sterilization procedures on alginate dispersions was studied by measuring viscosity and molecular weight changes. Autoclaving caused a 64% decrease in viscosity. Heating at a low temperature over several cycles was less efficient in sterilizing alginates and there was a progressive breakdown of the alginate chain over the succeeding cycles. Heating during ethylene oxide sterilization also resulted in reduced viscosity and breakdown. Membrane filtration yielded a sterile product with no significant reduction in viscosity or mol. wt.

Evaluation of the nebulisation of sodium ceftiofur in the treatment of experimental Pasteurella haemolytica bronchopneumonia in calves

Severe acute bronchopneumonia was induced in 24 conventional Friesian Holstein calves by inoculating them intratracheally with Pasteurella haemolytica type A1. Twelve of the calves were treated intramuscularly with sodium ceftiofur and 12 were treated with an aerosol of sodium ceftiofur. The mortality rate in the group of calves treated with the aerosol was significantly lower, and their clinical and haematological parameters returned to normal significantly faster than in the calves treated intramuscularly.

Sucrose laurate gels as a percutaneous delivery system for oestradiol in rabbits.

In this study sucrose laurate was formulated in hydrogels and investigated as a suitable transdermal penetration enhancer for oestradiol. Using rabbits as an animal model, the absolute bioavailability and the skin irritation were evaluated after single and multiple application. Three hydrogels containing 60 mg% oestradiol were evaluated: Oestrogel, and two hypromellose gels containing 5 and 15% sucrose laurate (w/w), respectively.

Sorption of isosorbide dinitrate to central venous catheters

Abstract— As several studies demonstrated the sorption of isosorbide dinitrate (ISDN) to intravenous delivery systems, a study on the sorption of ISDN to several central venous catheters was performed. Fourteen different catheters were perfused during a 2 h period, under simulated infusion conditions, with ISDN (250 μg mL−1) in 0·9% (w/v) sodium chloride. The drug loss to a polyethylene and a silicone catheter was 0·2 and 6·1%, respectively. The sorption to a polyvinylchloride heparin‐coated thermodilution catheter was 1–6·9% depending on the length of the catheter. The drug loss to polyurethane catheters of different composition varied between 3·8 and 28·9%. For polyurethane catheters composed of cycloaliphatic polyurethanes an inverse relation was shown between Shore A hardness and sorption.

Light stability of molsidomine in infusion fluids

Abstract— The influence of artificial light, daylight or stimulated sunlight on the stability of molsidomine was investigated. In static experiments an 80 μg mL−1 solution of molsidomine in saline was stored in an unprotected infusion bag. During dynamic experiments the molsidomine solution (80 μg mL−1) was dropped at 12·5 mL h−1 from an unprotected infusion bag, from an infusion bag covered with aluminium‐foil, or from an infusion bag protected with a UV‐cover. Either unprotected infusion tubing or infusion tubing with a UV‐filter were connected to the infusion bags. Static as well as dynamic experiments showed a half‐life of about 20 min for the unprotected molsidomine solutions, when placed behind a window during a sunny day. Protection from light of the infusion bag but not of the infusion tubing had only a minor influence on the drug half‐life. Protection of the infusion bag and the infusion tubing with a UV‐filter increased the half‐life to several days. These results confirm that both the infusion bag and the infusion tubing need adequate light protection during molsidomine administration.

Stability of topical erythromycin formulations

Abstract The stability of erythromycin, suspended in a w/o and an o/w emulsion or dissolved in an alcoholic solution and gel, was tested over a 12 week period. The influence of pH and storage temperature was evaluated. A shift in pH from 6.3 to 8.5 as well as an increase in storage temperature from 4°C to 25°C seemed to decrease the stability of erythromycin. The activity of erythromycin in emulsions with an aqueous phase of pH 8.5 had only 40% of the original activity after 1 month storage at 25°C. The alcoholic solution and gel retained more than 90% of their initial activity after 1 month storage at 25°C.