Research Articles
Amphiphilic β-Cyclodextrins Modified on the Primary Face: Synthesis, Characterization, and Evaluation of Their Potential as Novel Excipients in the Preparation of Nanocapsules

https://doi.org/10.1002/jps.10105Get rights and content

Abstract

The purpose of this study was to synthesize and characterize amphiphilic β-cyclodextrins modified on the primary face with substituents of varying chain lengths (C6 and C14) and bond types (ester or amide). We also aimed to evaluate the potentiality of the new amphiphilic β-cyclodextrins as excipients for the preparation and optimization of nanocapsules without using surface-active agents. Amphiphilic β-cyclodextrin derivatives were characterized by 1H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, mass spectroscopy, differential scanning calorimetry, and elemental analysis. Nanocapsules prepared by nanoprecipitation were characterized by particle size and zeta potential determination and freeze fracture followed by transmission electron microscopy. The appropriate amphiphilic β-cyclodextrin and its optimum concentration to be used were determined. Formation and characteristics of the nanocapsules were highly dependent on the structural properties of the modified cyclodextrin, its behavior in the oil–water interface and the viscosity and miscibility of the organic solvent with water. Physical stability after 5-month storage was also evaluated. The results indicated that derivatives with 6C aliphatic chains on the primary face proved to be the most efficient among the amphiphilic β-CDs in this study. They avoid the use of surfactants in parenteral formulations of nanocapsules. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 1214–1224, 2002

Section snippets

INTRODUCTION

Cyclodextrins are enzymatic degradation products of starch, consisting of glucopyranose units linked by α(1–4) bonds. They have been used as pharmaceutical excipients to formulate poorly soluble or instable drugs, as well as to mask the undesired effects of certain active ingredients by formation of inclusion complexes attributed to their hydrophilic surface and hydrophobic cavity.1,2 However, the configuration of natural cyclodextrins that allows inclusion of drugs, results in poor interaction

Materials

β-cyclodextrin, 100% pure according to nuclear magnetic resonance (NMR) spectroscopy was extensively dried under vacuum over phosphorous pentoxide before use. Chemical reagents were used as received. Dimethylformamide (DMF) was distilled and kept on molecular sieves (4 Å). Thin layer chromatography was performed on aluminum sheets coated with silica gel (Merck 60F254, USA) using detection by charring with 10% alcoholic sulfuric acid after elution with chloroform/methanol/20% ammonia (60:20:1)

Characterization of Amphiphilic β-Cyclodextrins

The amphiphilic β-cyclodextrins modified on the primary face were characterized using spectroscopic (1H-NMR, Mass, FTIR) and thermal methods (DSC) along with elemental analysis, solubility in different solvents, and theoretical HLB calculation. Thermal and spectroscopic characterization data are given in the Analytical Methods and Characterization section. Table 1 summarizes physicochemical properties of the new amphiphilic β-cyclodextrins.

Physicochemical Properties of Amphiphilic β-Cyclodextrins

Table 2 presents some of the physicochemical properties

DISCUSSION

Structural properties and selective substitution of cyclodextrins were assured by the optimized synthesis conditions and the resulting H-NMR and MS. This confirmation was essential to clarify the fact that chemical modifications of cyclodextrins may sometimes result in products that are statistical mixtures of over- and under-acylated cyclodextrins which can easily form nanoparticulate systems but cannot fully be characterized because of their impure structure.3,22, 23, 24, 25, 26

It was

CONCLUSION

In the light of these data, it can be observed that it is possible to obtain amphiphilic β-cyclodextrins modified on the primary or secondary face using conventional synthetic methods. Because of their chemical structures, each amphiphilic β-CD shows a different solubility profile and interfacial behavior. Suitable organic solvents should be used in the preparation of nanocapsules with amphiphilic β-cyclodextrins.

According to their nanocapsule forming properties, it is more appropriate to use

Acknowledgements

The authors acknowledge the financial support of EGIDE French Ministry of Foreign Affaires and TUBITAK-CNRS Turkish-French Scientific and Technical Collaboration Program. They also acknowledge the collaboration of Dr. Françoise Gaill, Dr. Jean-Pierre Lechaire, and Ms. Ghislaine Frébourg from Service de Microscopie Electronique de l'IFR la Région Ile de France for freeze fracture process and TEM analysis.

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