Comparative rheological investigation of crude gastric mucin and natural gastric mucus.

Mucus is a viscoelastic gel covering the entire alimentary tract. It represents a pre-epithelial diffusion barrier influencing the drug absorption process. In this way the rheological properties of mucus play an important role. The purpose of our investigation was to evaluate and compare the rheological properties of rehydrated dried crude porcine gastric mucin (Sigma mucin) and isolated natural porcine gastric mucus. Two different rheological approaches were used: constant shear and oscillatory shear conditions. The results obtained under steady shear conditions show that the reduction of apparent viscosity is caused by time, shear rate and temperature. With increasing Sigma mucin concentration the rheological behaviour changes from time-independent systems fitting in with the Casson model to time-dependent systems fitting in with the Herschel-Bulkley rheological model. Measurements performed under oscillatory shear conditions clearly show how the mechanical response of different concentrated systems has changed from dispersions with prevailing plastic to prevailing elastic properties. Mechanical deformation and frequency response of natural gastric porcine mucus have shown a strong gel structure with elastic properties. Comparing both systems it can be concluded that after rehydration of dried crude gastric porcine mucin, a model mucus system with rheological properties equivalent to natural mucus cannot be obtained.

Viscosity prediction of lipophilic semisolid emulsion systems by neural network modelling.

Previously published data (Gasperlin et al., 1998) on viscoelastic behaviour of lipophilic semisolid emulsion systems and the prediction of their physical stability by neural network modelling are analysed in further detail. Most attention has been paid to viscosity, which with storage (G') and loss modulus (G"), is one of the most important rheological parameters influenced by structure. Complex dynamic viscosity (eta*) was measured by oscillatory rheometry. The viscosity dependence of the lipophilic semisolid emulsions on the ratio of the particular components was defined by the neural network (error back-propagation algorithm), linear and incomplete polynomial models of higher orders. Polynomial models were used to complement the neural network model and to determine the relationship between variables. Since the viscosity was expressed in the whole measured frequency range, modelling was more complex and indirect modelling was introduced. The determined models were tested and the results confirm their usefulness for the explanation and prediction of the rheological characteristics of emulsion systems. The trained and tested neural network model proved to be a highly effective and applicable tool for predicting the viscosity of a lipophilic semisolid emulsion system of given composition.

Compatibility study between acetylcysteine and some commonly used tablet excipients.

Differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), HPLC and TLC were used to investigate the interactions between the mucolytic drug acetylcysteine and a number of commonly used tablet and capsule excipients. Acetylcysteine was found to be compatible with microcrystalline cellulose (Avicel PH 101), sodium carboxymethylcellulose, amorphous silicon dioxide (Aerosil), PVP, cross-linked PVP (Polyplasdone XL), corn starch, saccharose and magnesium stearate. Acetylcysteine thermal stability (onset degradation temperature) was decreased in mixtures with corn starch, magnesium stearate, saccharose and lactose. Interactions of acetylcysteine with lactose, PEG 4000 and 6000, glycine, adipic acid and saccharin sodium were found using DSC and studied in detail with FT-IR, HPLC and TLC. The results suggest that acetylcysteine in mixtures with PEG 4000, glycine or saccharin sodium is degraded during storage at conditions of high temperature and humidity.

[The influence on some physicochemical parameters on drug release from PMMA salt hydrogels]. / Einfluss einiger physikochemischer Parameter auf die Wirkstofffreisetzung aus PMMA-Salz-Hydrogelen.

In vitro drug liberation results from PMMA (Eudispert)-salt hydrogels are explained from the aspect of polymer concentration, polymer molecular mass, viscosity as well of neutralisation grade and cation (Na+, K+, NH+4, ethanolamine, triethanolamine) of the polymer molecule and solubility properties of the drugs. Drug diffusion through hydrogel is regulated with the polymer network, in dependence of polymer nature and further with die mobility of water. The considered influences predominantly cover each other.

[Drug liberation from dermatica (author's transl)]. / Wirkstoff-Freisetzung aus Dermatica.

Investigated 0,1% ointments based on oleogels, hydrogels and O/W creams show differences by in-vitro evaluation of dexamethasone sodiumphosphate and dexamethasone release, which we have evaluated concerning the vehicle composition and its viscosity, the internal structure of systems and the drug properties. The results show dependence of drug availability on the vehicle gel structure order on the one, and on the drug activity on the other hand. The presence of a hydrocolloid (Eudispert-Na) in O/W creams improves the drug release.

Influence of liposome bilayer fluidity on the transport of encapsulated substance into the skin as evaluated by EPR.

PURPOSE: The influence of liposome composition on the bilayer fluidity and on the transport of encapsulated substance into the skin was investigated. METHODS: Multilamellar vesicles (MLV) from dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) with various amounts of cholesterol were prepared by the film method and characterised by photon correlation spectroscopy and electron paramagnetic resonance (EPR) methods. The transport of the hydrophilic spin probe encapsulated in MLV into pig ear skin was investigated by EPR imaging methods. The bilayer domain structure was studied by fitting the lineshape of the experimental EPR spectra with the spectra calculated by the model, which takes into account the heterogeneous structure of the bilayer with several coexisting domains. RESULTS: Cholesterol strongly influences the entrapped volume of liposomes, the domain structure of the lipid bilayer, and the transport of hydrophilic spin probe into the skin. Transport was not observed for liposomes composed of phospholipid:cholesterol 1:0 or 9:1 (mol:mol), not even above the phase transition temperature from the gel to the liquid crystalline phase of DMPC. A significant delivery of hydrophilic spin probe was observed only if there was 30 or 50 mol% of cholesterol in the liposome bilayer. CONCLUSIONS: It can be concluded that the domain structure of the liposome bilayer is more important for the delivery of encapsulated substance into the skin than the liquid crystalline phase of the pure phospholipids bilayer.

Molecular motion of drugs in hydrocolloids measured by electron paramagnetic resonance.

The effects of a polymer, the Li-salt copolymer of methylmethacrylic acid, and its methyl ester on the motion of drug molecules in hydrocolloids were studied. The investigation was carried out by means of electron paramagnetic resonance (EPR) using the model nitroxide tempol, and the spin-labeled drugs lidocaine (sl-lid) and dexamethasone (sl-dex). Synthesis of sl-dex was performed. Spin-labeled molecules dissolved in hydrocolloids undergo a fast reorientation motion. The decreasing order of rotational correlation times (tau)--sl-dex greater than sl-lid greater than tempol--suggests that the size and the shape of the molecules strongly affect their motion. The inhibition of motion of larger molecules depends also on their flexibility. The tau values indicate proportionality of the microviscosity of hydrocolloids to the polymer concentration. Rotational motion is dependent on the local environment conditioned by the free spaces between polymer molecules.

Efficiency and usability of silicone surfactants in emulsions.

Synopsis The critical micelle contration (CMC) of silicone surfactants was determined to provide their optimal efficiency in emulsion systems. The lowest CMC value was found for the amphionic polysiloxane polyorganobetaine copolymer, which is undoubtedly the consequence of electrostatic repulsion preventing the aggregation of ionized molecules. Also the nonionic surfactants (polydimethyl siloxane polyethers) showed some differences: the surfactant with polyethylene oxide side chain is more effective compared to the polyethylene-polypropylene oxide side chain. The results of miscibility testing of silicone surfactants with common components of emulsions and creams confirm that not only silicone oils, but also silicone surfactants, should be considered as both explicitly hydrophobic and non lipophilic. The stability of emulsions containing silicone surfactants prepared by cold emulsification supported the incorporation of polyelectrolyte sodium carboxymethylcellulose, which increased viscosity of the continuous phase and prevented coalescence. The physical stability testing of prepared emulsions confirms that the used methods - centrifugation, particle size analysis and the observation of ageing at room (20-25 degrees C) and elevated temperature (40 degrees C) - give comparable results.