An interesting strategy for protecting skin from excessive exposure to free radicals is to support the skin endogenous antioxidant system. As the balance between different skin antioxidants is very ...important, a combined therapy using at least two antioxidants is desirable. In the present work, o/w, w/o, and gel-like microemulsions (ME), all composed of the same ingredients, were selected as carrier systems for dermal delivery of vitamins C and E. Gel-like ME was found to offer the best protection for both vitamins, although other ME also significantly increased their stability compared with that solution. In the presence of vitamin C no decrease in vitamin E content occurred. To obtain ME appropriate for dermal use, their viscosity was increased by adding thickening agents. On the basis of visual examination of viscosity and physical stability of thickened systems, several thickeners were selected. The addition of thickener significantly increased the viscosity of ME and changed the behavior of systems from ideal Newtonian to thixotropic. Finally, the stability of both vitamins was examined as a function of thickening agent and of the location of vitamins in the ME. The addition of thickeners changed the stability of at least one vitamin, but the systems generally still protected vitamins better than solutions. It is likely that the changes in internal organization of ME resulting from the addition of thickener, confirmed by thermal analysis and changes in solubility of oxygen in the outer phase, were the most important factors that influenced the stability of vitamins in thickened systems.
Antioxidants provide the mainstay for skin protection against free radical damage. The structure of microemulsions (ME), colloidal thermodynamically stable dispersions of water, oil and surfactant, ...allows the incorporation of both lipophilic (vitamin E) and hydrophilic (vitamin C) antioxidants in the same system. The objective of this work was to investigate the potential of non-thickened (o/w, w/o and gel-like) and thickened (with colloidal silica) ME as carriers for the two vitamins using reconstructed human epidermis (RHE). The amounts of these vitamins accumulated in and permeated across the RHE were determined, together with factors affecting skin deposition and permeation. Notable differences were observed between formulations. The absorption of vitamins C and E in RHE layers was in general enhanced by ME compared to solutions. The incorporation of vitamins in the outer phase of ME resulted in greater absorption than that when vitamins were in the inner phase. The location of the antioxidants in the ME and affinity for the vehicle appear to be crucial in the case of non-thickened ME. Addition of thickener enhanced the deposition of vitamins E and C in the RHE. By varying the composition of ME, RHE absorption of the two vitamins can be significantly modulated.
One of the greatest challenges in the pharmaceutical science is the improvement of oral bioavailability of poorly soluble drugs. Lately, one of the most attractive approaches has been formulation of ...lipid based drug delivery systems. However, the emerging popularity of these systems in the last decade has brought to light the need for efficient methods for their in vitro evaluation that would serve as their in vivo behaviour prediction tool. Because lipids are subject to lipid digestion and multiple absorption pathways in vivo, simple dissolution tests are not predictive enough when testing lipid based delivery systems. To assert these needs, the in vitro lipolysis model has been developed, utilizing pancreatic enzymes, bile and phospholipids in a temperature controlled chamber to simulate in vivo digestion. However, with very variable physiological conditions in gastrointestinal tract, this model has not been yet standardised and experiments vary among different laboratories. This review discusses in vivo events following oral application of lipid based delivery, in vitro lipolysis models to emulate them and their future perspectives.
The drug delivery potential of liquid crystals (LCs) for ascorbyl palmitate (AP) was assessed, with the emphasis on the AP stability and release profile linked to microstructural rearrangement taking ...place along the dilution line being investigated by a set of complementary techniques. With high AP degradation observed after 56 days, two stabilization approaches, i.e., the addition of vitamin C or increasing AP concentration, were proposed. As a rule, LC samples with the lowest water content resulted in better AP stability (up to 52% of nondegraded AP in LC1 after 28 days) and faster API release (~18% in 8 h) as compared to the most diluted sample (29% of nondegraded AP in LC8 after 28 days, and up to 12% of AP released in 8 h). In addition, LCs exhibited a skin barrier-strengthening effect with up to 1.2-fold lower transepidermal water loss (TEWL) and 1.9-fold higher skin hydration observed in vitro on the porcine skin model. Although the latter cannot be linked to LCs’ composition or specific microstructure, the obtained insight into LCs’ microstructure contributed greatly to our understanding of AP positioning inside the system and its release profile, also influencing the overall LCs’ performance after dermal application.
Sodium ascorbyl phosphate in topical microemulsions Špiclin, Polona; Homar, Miha; Zupančič-Valant, Andreja ...
International journal of pharmaceutics,
04/2003, Volume:
256, Issue:
1
Journal Article, Conference Proceeding
Peer reviewed
Sodium ascorbyl phosphate is a hydrophilic derivative of ascorbic acid, which has improved stability arising from its chemical structure. It is used in cosmetic and pharmaceutical preparations since ...it has many favorable effects in the skin, the most important being antioxidant action. In order to achieve this, it has to be converted into free ascorbic acid by enzymatic degradation in the skin. In the present work, o/w and w/o microemulsions composed of the same ingredients, were selected as carrier systems for topical delivery of sodium ascorbyl phosphate. We showed that sodium ascorbyl phosphate was stable in both types of microemulsion with no significant influence of its location in the carrier system. To obtain liquid microemulsions appropriate for topical application, their viscosity was increased by adding thickening agents. On the basis of rheological characterization, 4.00% (m/m) colloidal silica was chosen as a suitable thickening agent for w/o microemulsions and 0.50% (m/m) xanthan gum for the o/w type. The presence of thickening agent and the location of sodium ascorbyl phosphate in the microemulsion influenced the in vitro drug release profiles. When incorporated in the internal aqueous phase, sustained release profiles were observed. This study confirmed microemulsions as suitable carrier systems for topical application of sodium ascorbyl phosphate.
We assessed the functionality of sucrose esters (sucrose laurate, myristate, palmitate, and stearate), relatively innocuous nonionic surfactants, in formulation of biocompatible microemulsions. The ...putative influence of surfactant structure on the extension of microemulsion region was explored through the construction of the pseudo-ternary phase diagrams for the isopropyl myristate/sucrose ester-isopropyl alcohol/water system, using the titration method and mixture experimental approach. Minor changes in surfactant tail length strongly affected the microemulsion area boundaries. D-optimal mixture design proved to be highly applicable in detecting the microemulsion regions. Examination of conductivity, rheology, and thermal behavior of the selected sucrose laurate and sucrose myristate-based microemulsions, upon dilution with water, indicated existence of percolation threshold and suggested the phase inversion from water-in-oil to oil-in-water via a bicontinuous structure. Atomic force micrographs confirmed the suggested type of microemulsions and were valuable in further exploring their inner structure. The solubilization capacity of aceclofenac as a model drug has decreased as the water volume fraction in microemulsion increased. High surfactant concentration and the measured solubility of aceclofenac in microemulsion components suggested that the interfacial film may mostly contribute to aceclofenac solubilization.
Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid ...dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.
The aim of this work was to test innovative approach for enhancing ascorbyl palmitate stability in microemulsions for topical application by addition of newly synthesized co-antioxidant ...4-(tridecyloxy)benzaldehyde oxime (TDBO) and to investigate its antioxidant activity and finally to evaluate cytotoxicity of TDBO-loaded microemulsions on keratinocyte cells. TDBO significantly increased ascorbyl palmitate stability in oil-dispersed-in-water (o/w) microemulsions, most presumably due to reduction of ascorbyl palmitate radical back to ascorbyl palmitate, since TDBO free-radical scavenging activity was confirmed. Cytotoxicity experiments demonstrated no significant change in cell viability or morphology in the presence of TDBO-loaded microemulsions regarding unloaded microemulsions, although greater cytotoxicity was observed with increased microemulsion concentrations. Therefore, the incorporation of TDBO as non-cytotoxic co-antioxidant in o/w microemulsions is a promising new strategy for enhancing ascorbyl palmitate stability that could be used to support antioxidant network in the skin.
Small-angle X-ray scattering technique has been used to study the structural properties of the quaternary microemulsion Tween 40
®/Imwitor 308
®/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., Bešter-Rogač, M., Gašperlin, 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.
Active compounds can be protected against degradation by incorporation into colloidal carrier systems. The stabilizing effect of carrier systems for ascorbyl palmitate (AP) was investigated using ...microemulsions (ME), liposomes and solid lipid nanoparticles (SLN). Analysis of chemical stability by HPLC showed that AP is most resistant against oxidation in non-hydrogenated soybean lecithin liposomes, followed by SLN, w/o and o/w ME, and hydrogenated soybean lecithin liposomes. The molecular environment of the AP-like nitroxide probe (C
16-Tempo) in colloidal carriers was characterized using electron paramagnetic resonance (EPR) spectroscopy. We have found that the nitroxide groups are located in environments with different polarity and mobility. The hydrophilic part of AP is the reactive moiety, and high stability is obtained in systems in which this part is exposed to a less polar environment. Additionally, the determined accessibility of nitroxide groups to reduction correlated well with the chemical stability of AP. It is more deeply immersed in the interface when entrapped in a liquid-state carrier than when applied in gel-state particles. Encapsulation of AP in SLN core leads to greater stability. We conclude that the location of the sensitive group of the drug-molecule in a carrier system is crucial for its stability.
PDF
