Mirjana Gašperlin

Sodium ascorbyl phosphate in topical microemulsions

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.

Stability of ascorbyl palmitate in topical microemulsions

Ascorbyl palmitate and sodium ascorbyl phosphate are derivatives of ascorbic acid, which differ in stability and hydro-lipophilic properties. They are widely used in cosmetic and pharmaceutical preparations. In the present work the stability of both derivatives was studied in microemulsions for topical use as carrier systems. The microemulsions were of both o/w and w/o types and composed of the same ingredients. The stability of the less stable derivative ascorbyl palmitate was tested under different conditions to evaluate the influence of initial concentration, location in microemulsion, dissolved oxygen and storage conditions. High concentrations of ascorbyl palmitate reduced the extent of its degradation. The location of ascorbyl palmitate in the microemulsion and oxygen dissolved in the system together significantly influence the stability of the compound. Light accelerated the degradation of ascorbyl palmitate. In contrast, sodium ascorbyl phosphate was stable in both types of microemulsions. Sodium ascorbyl phosphate is shown to be convenient as an active ingredient in topical preparations. In the case of ascorbyl palmitate, long-term stability in selected microemulsions was not adequate. To formulate an optimal carrier system for this ingredient other factors influencing the stability have to be considered.

Effect of colloidal carriers on ascorbyl palmitate stability

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.

The structure elucidation of semisolid w/o emulsion systems

Abstract 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.

Skin protection against ultraviolet induced free radicals with ascorbyl palmitate in microemulsions

UV irradiation induces free radical formation in the skin. UV filters and antioxidants can be used for protection. In the present work, the amphiphilic antioxidant ascorbyl palmitate has been investigated and its effectiveness against free radical formation in porcine skin determined with electron paramagnetic resonance (EPR) spectroscopy with a spin trapping technique. 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) was used as spin trap. In this study, three different radicals were identified in UV irradiated porcine ear skin: two originated from sulphur centred radicals (SO(3)*), while the third was the carbon-centred acyl (C=O*) radical. Ascorbyl palmitate applied on the skin decreased the level of formation of free radicals. Its effectiveness depended significantly on the carrier system - the type of microemulsion and its concentration, while the time of application had no influence on its effectiveness. Oil in water microemulsions delivered ascorbyl palmitate to the skin significantly better than water in oil microemulsions. In both types of microemulsions, the effectiveness increases at higher concentrations of ascorbyl palmitate.

Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs

Abstract Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemulsion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions.

Simultaneous absorption of vitamins C and E from topical microemulsions using reconstructed human epidermis as a skin model

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.

Temperature-Sensitive Microemulsion Gel: An Effective Topical Delivery System for Simultaneous Delivery of Vitamins C and E

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.

Stability of Vitamins C and E in Topical Microemulsions for Combined Antioxidant Therapy

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.

Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups

Introduction: Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system. Areas covered: Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling. Mini-tablet production is similar to the production of standard tablets but requires excellent powder flow due to the small dies, exact control of process parameters and special caution during tablet press assembly in order to avoid tool damage. Mini-tablets (coated or uncoated and single- or multiple-unit systems) are mainly developed as patient-friendly systems for pediatric and geriatric patients and also for personalized medicine because they offer improved swallowing and flexible dosing, combining various release kinetics, doses and active compounds in only one system. Mini-tablets may also be successfully used as multiple-unit modified release systems (extended release, delayed-colon release, pulsatile and bi-modal release and gastroretentive systems) providing improved drug bioavailability compared with single-unit systems. Expert opinion: Mini-tablets used as single- or multiple-unit oral dosage forms have enormous potential as a patient-friendly drug delivery system for targeted populations, providing improved swallowing, flexible dosing and a combination of different release patterns and/or different active compounds (decreasing dosing frequency and/or polypharmacy therapy problems). In terms of complete expression of the benefits of mini-tablets over other oral dosage forms on the market, further investigation in formulation possibilities and development of suitable dosing devices is of essential importance.