The aim of the study was to evaluate a hot-melt technique for preparation of immediate release spherical microparticles containing clarithromycin with acceptable characteristics and process yield. A ...modified fluid bed apparatus with rotor insert was used to prepare spherical microparticles in the size range of 125-355 µm. Poloxamer 188, PEG-32 glyceryl laurate (Gelucire 44/14) and a mixture of polyethylene glycol (PEG) 4000 with PEG 400 were used as meltable binders. Key process parameters were identified and optimized and their influence on process yield and microparticles characteristics was determined. Microparticles with poloxamer 188 and PEG exhibited relatively good mechanical properties. Process yield was around 70% and 60% in the case of PEG and poloxamer 188 respectively. Microparticles prepared with PEG-32 glyceryl laurate exhibited poor mechanical properties and process yield compared to other microparticles. The process was shown to be limited by the bed temperature, exhibiting the best process stability with poloxamer 188 followed by PEG and PEG-32 glyceryl laurate. Dissolution rate and equilibrium concentration of clarithromycin released from prepared microparticles was improved compared to similar particles prepared by wet granulation.
Microcapsules with self-microemulsifying core were originated by the vibrating nozzle method. Alginate-pectin (A/P) ratio of the shell forming phase was optimized with regard to core phase retention ...and drug release kinetics from dried microcapsules. Well shaped microcapsules with high encapsulation efficiency were produced when an A/P composition of 25:75 was used. Microcapsules with higher pectin content exhibited faster drug release, which was additionally enhanced by the addition of sodium chloride to the shell phase.
The purpose of this study was to predict microemulsion structures by creating two artificial evolutionary neural networks (ANN) combined with a genetic algorithm. The first ANN would be able to ...determine the type of microemulsion from the desired composition, and the second to determine the type of microemulsion directly from a differential scanning calorimetry (DSC) curve.
The algorithms and the structures for each ANN were constructed and programmed in C++ computer language. The ANNs had a feedforward structure with one hidden level and were trained using a genetic algorithm. DSC was used to determine the microemulsion type.
The ANNs showed very encouraging accuracy in predicting the microemulsion type from its composition and also directly from the DSC curve. The percentage success, calculated over the tested data, was over 90%. This enabled us, with satisfactory accuracy, to construct several pseudoternary diagrams that could facilitate the selection of the microemulsion composition to obtain the optimal desired drug carrier.
The ANN constructed here, enhanced with a genetic algorithm, is an effective tool for predicting the type of microemulsion. These findings provide the basis for reducing research time and development cost for characterizing microemulsion properties. Its application would stimulate the further development of such colloidal drug delivery systems, exploit their advantages and, to a certain extent, avoid their disadvantages.
Microemulsions (ME)—nanostructured systems composed of water, oil, and surfactants—have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this ...work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-like ME with temperature-sensitive rheological properties was formed. The temperature-driven changes in its microstructure were confirmed by rotational rheometry, viscosity measurements, and droplet size determination. The release studies have shown that the vitamins’ release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). According to effectiveness in skin delivery of both vitamins, o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer, indicating that no simple correlation between vitamins release and skin absorption could be found. The cytotoxicity studies revealed good cell viability after exposure to ME and confirmed all tested microemulsions as nonirritant.
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.
Previously published data (
Gašperlin 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.
Background: Colloidal silica is the thickener of interest for topical formulations and can therefore be used to optimize the viscosity of both hydrophilic and lipophilic microemulsions (MEs). To the ...best of our knowledge, no information is available about the effect of topically applied colloidal silica on skin penetration of drugs. So, our aim was to determine its influence on the effectiveness of ME in the simultaneous delivery of vitamins C and E to the skin. Methods: Two different aspects of silica possible function were investigated. Its effects on formulation characteristics were studied by determination of partition coefficient of the vitamins, their solubility and release profile. The direct impact of silica on the skin was further evaluated by transepidermal water loss measurements, scanning electron microscopy (SEM), and cell toxicity determination (MTT assay). Results: The addition of colloidal silica to ME was shown to increase significantly the vitamins' solubility and their partition to the phase in which they were less soluble. Its presence also increased the amount of both vitamins in epidermis, which was confirmed by release studies. Furthermore, we demonstrated that colloidal silica interacts with excised skin. It decreased transepidermal water loss, probably by retaining water in the stratum corneum because of its massive accumulation in the upper layers, as revealed by SEM. Conclusion: The results confirmed that addition of colloidal silica in ME simultaneously loaded with vitamins C and E enhanced vitamins' skin bioavailability by its dual influence on delivery characteristics of ME as well as on skin properties.
Small-angle X-ray scattering technique has been used to study the structural properties of the quaternary microemulsion Tween 40 super(registered)/Imwitor 308 super(registered)/isopropyl ...myristate/water and of five-component system obtained by the addition of the drug ketoprofen to the original quaternary system. The results enlighten the structuration of the studied systems and represent new complementary findings to the previous study Podlogar, F., Bester-Rogac, M., Gasperlin, M., 2005. The effect of internal structure of selected water-Tween 40 (R)-Imwitor 308 (R)-IPM microemulsions on ketoprofene release. Int. J. Pharm. 302, 68-77 on the correlation between the structuration of these systems and the release rates of the ketoprofen. The present results indicate that in the samples with the moderate to high concentration of water where the latter is a continuous phase the addition of smaller amounts of the ketoprofen does not change their inner structuration significantly. The quaternary sample containing 46.2 wt.% of water seems to be very near the composition where the transition from the bicontinuous to the lamellar structure of the microemulsion occurs. In the samples containing from 46.2 to 62.7 wt.% of water the swelling of lamellar phases with constant thickness of double-layer can be characterized. At approximately the latter composition another noticeable transition in the inner structuration of the microemulsion has been observed. Interestingly, all these changes in the inner structuration of the studied systems did not affect the trend of the drug release rates in this regime of water concentrations.
Encapsulation of natural antioxidant resveratrol in liposomes Isailović, Bojana D. (Faculty of Technology and Metallurgy, Belgrade (Serbia)); Kostić, Ivana T. (Faculty of Technology and Metallurgy, Belgrade (Serbia)); Zvonar, Alenka (Faculty of Pharmacy, Ljubljana (Slovenia)) ...
Proceedings of 6th Central European Congress on Food - CEFood Congress,
2012
Conference Proceeding
Liposomes have been shown to be suitable systems for encapsulation and preserving the health–beneficial properties of a wide range of biological active ingredients such as resveratrol (RSV). The aim ...of this study was to encapsulate RSV in liposomes, with a goal to achieve the extended release and improved stability of RSV. Multilameral liposomes were prepared by means of two different methods: thin film method (TF) and proliposome method (PRO). In both methods, the ratio between added RSV and phospolipon 90G (P90G) was 1:20 w/w. Extrusion and sonication were applied in order to obtain unilameral liposomes. Both methods were efficient in capturing RSV within the microparticles, thus encapsulation efficiency had high values (92,9% in case of TF and 97,4% in case of PRO). The size reduction of liposomes resulted with particles of the average diameter ranged between 120 and 270 nm. Antioxidative activity was retained at a high level (approximately 95%). Franz diffusion cell was used for release studies and diffusion of RSV was monitored for 6h. According to the results, liposomes appeared to be suitable vehicles for encapsulation of resveratrol where PRO is particularly useful for encapsulation of antioxidants.
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