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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 ( η *) 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.

The influence of different ratios of individual components (silicone surfactant, hydrophilic and lipophilic phase) on the viscoelastic behaviour of semisolid lipophilic emulsion systems was studied. The creams were prepared according to a preliminary experimental design (mixture design). The content of all three phases was varied: surfactant (1–5%), purified water (from 40 to 90%) and white petrolatum (5–59%). Oscillatory rheometry was used as the most appropriate experimental method for the evaluation of the emulsions. The rheological properties were influenced by the ratio of the components. For highly concentrated systems the predominant elastic response in the whole frequency range was measured. The cross-over point is characteristic for the concentrated systems. For the low concentrated systems, viscous behaviour is predominant. Rheometry has also been employed to follow and evaluate physical stability as one of the critical factors of emulsion systems. The dynamic rheological parameter, tan δ , has been chosen as the basis for developing mathematical models (linear, polynomial, neural) to forecast stability related to the content of the separate components in emulsion systems. After testing the linear models their non agreement to statistical criteria for a good model F reg , F lof , CC, DC, and RMS was found. The two-level neural network has been proven to be a statistically acceptable model, as were the polynomials of the second order. The two-level neural network model was also evaluated and the results have shown a great degree of reliability. The prediction of tan δ using a neural network model was found to be of great interest for the contemporary pharmaceutical formulation design because a lot of additional testing can be omitted.

Purpose. The influence of liposome composition on the bilayer fluidity and on the transport of encapsulated substance into the skin was investigated.

In the course of investigating the effects of silicone surfactant (Abil WE 09®) on the microstructure of semisolid w/o emulsion systems with different water/oil ratios, only dispersed droplets of the internal water phase (1–15 μm size) were discovered in the gel network of white petrolatum. With increasing water content (from 40 to 90% w/w) the degree of dispersity was found to increase (microscopic analysis-polarized light microscopy and TEM). Experiments were also carried out using differential scanning calorimetry (DSC) and rheometry (rotational and oscillatory viscosimetry). The DSC results showed different behaviour of the investigated systems on controlled cooling. In semisolid emulsion systems with droplets small enough and of equal size, a homogeneous nucleation temperature was achieved. In emulsion systems containing a high percentage of water, the assumption that the behaviour of water was like that of the pure (bulk) water was acceptable. All semisolid emulsion systems exhibited pseudoplastic behaviour. Their viscoelastic properties determined using oscillation rheometry correlated well with rotational results.

The hydrolysis of the chemisorbate of p -hydroxybenzoic acid methyl ester (PHBAME) on porous silica (KG 100) incorporated in lipophilic vehicles such as liquid paraffin, synthetic oil Miglyol® 818 and white petrolatum was examined in dissolution media at pH 2 and 7.4, respectively. Chemisorbed PHBAME on KG 100 is released more rapidly in alkaline than in acidic dissolution fluids. Dispersions of the PHBAME-KG 100 chemisorbate in lipophilic vehicles modify the hydrolysis significantly. Drug release from chemisorbate dispersed in lipophilic vehicles may be controlled by the polarity of the vehicles. However, the viscosity of the vehicle, and not the polarity, exerts the strongest influence on the drug release.

Chitosan, a natural, biocompatible polymer, is becoming popular in dosage form design. In our study the design factors affecting the release of lidocaine and lidocaine chloride from chitosan hydrocolloids and gels were studied. In hydrocolloids a relatively high viscosity was found at low concentrations of chitosan caused by the increased effective volume of the polymer molecules, due to the reflection of the same charges in the chains. The drug release is slow and sustained, being influenced by the chitosan content. The mechanism of chitosan gel formation is not known exactly, but it is clear that for gel formation the length of the chitosan chains and the degree of reacetylation are responsible. The release profile of gels follows almost zero order kinetics. Also, the degree of reacetylation is responsible for the release behaviour. The rotational motion of nitroxides (Tempol, spin-labeled lidocaine) determined by EPR experiments showed practically equal rotational motion at different degrees of reacetylation. Thus, it was concluded that the free spaces, available for nitroxide rotation, were not changed significantly. The degree of reacetylation affects the translational diffusion more strongly.

Felodipine (ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) was investigated by means of DSC, FTIR and X-ray diffraction and three different polymorphic forms, designated as I–III, respectively, were found. During heating, no interconversion of any polymorphic form took place. After cooling the felodipine melt (in liquid N2 or at ambient temperature) the glassy state was formed. The existence of glassy felodipine was confirmed by spin-lattice (T1) and spin-spin (T2) relaxation time measurements on a Bruker Pulse NMR spectrometer. During the heating of glassy felodipine recrystallization took place and two additional polymorphic forms, referred to as Im and IIIm, were observed.

The molar solubility of felodipine in water was calculated and experimentally determined. A polyoxyethylene-polyoxypropylene block copolymer (Synperonic T304) and sodium lauryl sulfate as surfactants and ethanol as cosolvent were used as solubilizing agents. Significantly different molar solubilities were determined for felodipine according to the approach used to achieve solubilization. Such differences are the result of the different mechanisms of solubilization of the additives.

The effects of a polymer, the Li-salt copolymer of methyl-methacrylic 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 (si-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 (τ) —sl-dex > si-lid > 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 τ 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.

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.

Through DSC and DDSC approach some findings in molecular pharmaceutics concepts of PEO suppositories were confirmed. It was stated that the cooling rate of solidification, core-crust location in suppository and aging, influence the nature of PEO 4000 structure.

The thermal behaviour of piroxicam (white anhydrous form) and its surface deposit (50 wt.%) on amorphous silicon dioxide was studied using TG and DSC techniques. On the basis of isothermal TG, thermal decomposition kinetic data were obtained and reaction mechanisms were established according to Sharp's method. It was found that the thermal decomposition of pure piroxicam was heterogeneous, but that the surface deposit decomposed homogeneously throughout the whole reaction.