Structural characterization and in vivo evaluation of retinyl palmitate in non-ionic lamellar liquid crystalline system

doi:10.1016/j.colsurfb.2011.02.027

Colloids and Surfaces B: Biointerfaces

Volume 85, Issue 2, 1 July 2011, Pages 182-188

https://doi.org/10.1016/j.colsurfb.2011.02.027 Get rights and content

Abstract

Carrier systems for lipophilic drugs, such as the liquid crystalline systems (LCS) have been extensively studied to improve effect and selectivity. Retinyl palmitate (RP) is widely used in pharmaceutical and cosmetics products to improve the skin elasticity. The aim of this study was the development, characterization and the in vivo effectiveness of RP in non-ionic LCS structures. LCS containing polyether functional siloxane as oil phase, silicon glycol copolymer as surfactant and water in the ratio 30:10:60, with and without RP were studied. The results of the polarized light microscopy, small-angle X-ray scattering and rheology analysis indicated the presence of typical LCS structures with lamellar arrangement. Regardless of the presence of RP, the rheological studies showed the pseudo plastic behavior of the systems. However, highest hysteresis area was verified when comparing the system in the presence and in the absence of RP. Stability study SAXS monitored, carried out up to 30 days in various storage temperature conditions (25 ± 2 °C, 37 ± 2 °C and 5 ± 2 °C) demonstrated the great structural stability of the LCS systems. The in vivo effectiveness analysis suggests that the RP-loaded LCS provided a significant reduction of the orbicular wrinkles in human volunteers (P = 0.048).

Graphical abstract

Highlights

► A non-ionic biocompatible liquid crystalline system as carrier of retinyl palmite (RP) for topical application was studied. ► Pseudo-ternary phase diagram was used for graphical characterization of the systems. ► Rheological analysis, polarized light microscopy and small-angle X-Ray scattering were used to characterize the structures of LCS according the phase diagrams. ► A significant in vivo reduction of the orbicular wrinkles in human volunteers was obtained with RP-loaded LCS structures.

Introduction

Carrier systems for lipophilic drugs, such as the liquid crystalline systems (LCS) have been extensively studied to improve effect and selectivity [1], [2], [3]. It is known that the LCS can provide appropriated response for prolonged time, improving drug efficacy and reducing side effects [4], [5], [6]. These systems can be administered by different routes including ocular, oral, intraperitoneal, intramuscular, subcutaneous and cutaneous [7], [8]. The development of new drug carrier systems based in the LCS structure has been a promising approach to increase and control the drug skin penetration [9], [10], [11], [12], [13]. Liquid crystalline phases are components mixtures that have mechanical properties of a liquid (fluidity) and optical characteristics of a crystal (optical anisotropy). Liquid crystalline systems are thermodynamically stable, thermotropic and lyotropic systems that can be stored for long periods without alterations [14], [15], [16], [17]. Lyotropic liquid crystalline phases can be used as topical drug delivery systems because the high ability of drug solubilization, thermodynamic stability, a wide range of rheological properties and the high similarity with the intercellular lipid membranes of the skin [18], [19], [20], [21]. Swarbrick and Siverly investigated the topical application of vehicles containing LCS and established that the percutaneous absorption of lipophilic drug model decreases significantly when the proportion of liquid crystalline phases increases above 5–10% [22]. LCS can control drug release because the low interfacial tension arising at oil–water interface [23], [24]. The mechanism involves the progressive diffusion into the skin and to systemic circulation [25], [26], [27]. They can bring a considerable increase in the solubility of poorly or water insoluble drugs [28], [29], [30], [31].

Appropriated methods of investigation and characterization of LCS are often used in drug development. Sophisticated techniques such as polarized light microscopy (PLM), ionic conductivity, rheology and small-angle X-ray scattering (SAXS) are available to achieve this goal [32].

The use of silicones in topical formulations is a world trend, due to their advantages like non-comedogenity, film formation, skin hydration, good skin feel and acceptance by the consumers. Thus, the association of LC and silicones allow for more stable and efficient formulations with adequate penetration, besides keeping the skin always moisturized [33], [34].

Retinol, the form of vitamin A absorbed from animal food sources, is a yellow, fat-soluble substance. Since the pure alcohol form is unstable, the vitamin is found in tissues in a form of retinyl ester. It is also commercially produced and administered as esters such as retinyl acetate or palmitate and is widely used as active substance in pharmaceutical topical formulations. RP improves the elasticity of the skin reducing up to 10% [35], [36], [37].

The aim of this study was the development, characterization, and in vivo effectiveness determination of the LCS containing RP. For this RP-unloaded and RP-loaded LCS, obtained from the combination of polyether functional siloxane as oil phase, silicon glycol copolymer as surfactant and water were used.

Section snippets

Material

Polyether functional siloxane (PFS), DC^® 5329 (S) and silicon glycol copolymer (SGC), DC^® 193 (O) were purchased from Dow Corning (Michigan, USA), retinyl palmitate (RP) 1,000,000 UI/g from Roche (Greenzach, Germany). The high purity water (W) from Millipore Milli-Q plus purification system was used throughout.

Formulations preparation

The samples were prepared by heating the mixture of O and S to 45 °C. The W was heated up to 40 °C was then carefully added under gentle and constant stirring until the mixture reaches at

Results and discussion

The data of the pseudo-ternary phase diagram shows that it is possible to add a great volume of oil phase and limited volume of water phase maintaining the thermodynamic stability of systems. Clear and translucent regions are obtained in a wide range region of the pseudo-ternary phase diagram (Fig. 1). The analysis of the phase diagram regions in Fig. 1 shows a distinct transition from LCS to VEM, TV and CL; and from LEM, LCS and CL to PS. Independently on the proportions of the S and O a

Conclusions

The studied systems containing Polyether functional siloxane, Polyether functional siloxane and water in its composition were able to form lamellar liquid crystalline phases. The systems were properly characterized by PLM and SAXS analysis. The rheological study showed that the formulations behave a non-Newtonian fluid, with characteristic of the pseudo-plastic material. The stability studies revealed that the presence of RP did not cause significant structural changes in the system. The

Acknowledgements

The authors wish to thank FAPESP, CNPq and CAPES for the financial support.

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Structural characterization and in vivo evaluation of retinyl palmitate in non-ionic lamellar liquid crystalline system

Abstract

Graphical abstract

Highlights

Introduction

Section snippets

Material

Formulations preparation

Results and discussion

Conclusions

Acknowledgements

Pharm. Sci. Technol. Today

Adv. Drug Deliv. Rev.

Adv. Drug Deliv. Rev.

Int. J. Pharm.

J. Control. Release

Adv. Drug Deliv. Rev.

J. Control. Release

Int. J. Pharm.

Colloids Surf. B

Colloids Surf. B

Colloids Surf. B

J. Control. Release

Curr. Opin. Colloid Interface Sci.

Colloids Surf. A: Physicochem. Eng. Aspects

J. Colloid Interface Sci.

Eur. J. Pharm. Sci.

Int. J. Pharm.

Eur. J. Pharm. Biopharm.

Adv. Colloid Interface Sci.

Phys. Rep.

Colloids Surf. A: Physicochem. Eng. Aspects

J. Colloid Interface Sci.

J. Pharm. Sci.

Int. J. Pharm.

J. Am. Acad. Dermatol.

Crit. Rev. Ther. Drug Carrier Syst.

Colloids Surf. B

Colloids Surf. B

Pharm. Res.

Colloids Surf. B