A New Approach for Quantitative Determination of γ-Cyclodextrin in Aqueous Solutions: Application in Aggregate Determinations and Solubility in Hydrocortisone/γ-Cyclodextrin Inclusion Complex

doi:10.1002/jps.24608

Journal of Pharmaceutical Sciences

Volume 104, Issue 11, November 2015, Pages 3925-3933

https://doi.org/10.1002/jps.24608 Get rights and content

ABSTRACT

Fast and simple high-pressure liquid chromatographic (HPLC) method with charged aerosol detector (CAD) was developed for quantitation of γ-Cyclodextrin (γCD) in aqueous solutions. The chromatographic system consisted of a C18 column (i.e., the stationary phase) and an aqueous mobile phase containing 7% (v/v) methanol. Calibration curve was obtained over the γCD concentration range of 0.005%–1% (w/v). The limit of detection and quantitation of γCD were 0.0001% and 0.0002% (w/v), respectively. Formation of γCD aggregates in aqueous solution and their critical aggregation concentration (cac) were determined by both conventional dynamic light scattering method and permeation method using HPLC-CAD for quantitative determination of γCD. The cac of γCD was determined to be 0.95% (w/v) and the amount of γCD self-aggregates increased with increasing γCD concentrations. Also, the developed HPLC-CAD method was used to determine the γCD phase-solubility profile in an aqueous hydrocortisone (HQ/γCD complexation medium. The maximum concentration of dissolved γCD and HC was determined to be 1.47% and 0.31% (w/v), respectively. The membrane permeation method was shown to be a reliable method for determination of metastable γCD aggregates. The HPLC-CAD method was successfully applied for quantitative determination of γCD in aqueous solutions during permeation and phase-solubility studies.

Section snippets

INTRODUCTION

Cyclodextrins γCDs) are cyclic oligosaccharides consisting of α-D-glucopyranose units. The most common CDs are composed of six (αCD), seven (βCD), and eight (γCD) units that form a hollow, truncated cone with a hydrophobic cavity and a hydrophilic outer surface (Fig. 1). CD is able to form an inclusion complex by taking up hydrophobic moiety or a small molecule into the central cavity. The hydrophilic exterior is responsible for the aqueous solubility of CDs and their complexes.¹ Previous

Materials

γ-Cyclodextrin was purchased from Wacker Chemie (Burghausen, Germany). Hydrocortisone (HC) was purchased from Fagron (Nieuwerkerk aan den Ussel, The Netherlands). Methanol was HPLC grade obtained from Sigma-Aldrich (St. Louis, Missouri, USA). All solutions and the mobile phase were prepared using Milli-Q water (Millipore, Billerica, Massachusetts). Semipermeable cellophane membranes Spectra/Por® (Spectrum Europe, The Netherlands) with MWCOs of 3.5–5, 8–10, 20, and 50 kDa were used for permeation

Validation

Calibration curves were prepared by plotting the peak area against the individual concentration on a log-log scale. The linear regression showed good relationship over a concentration range of 0.005%–1% (w/v). The mean values of y-intercept, slope, and correlation coefficient were 0.085 ± 1.47, 0.722 ± 0.05, and 0.995 ± 0.01, respectively.

The intraday precision and accuracy were tested at 0.25%, 0.75%, and 1.00% (w/v) of γCD. The aqueous 0.25% (w/v) γCD solution was injected directly into the HPLC,

CONCLUSIONS

The reverse-phase liquid chromatography method provided a good linearity, precision, and accuracy for determination of γCD in aqueous solutions. This method can readily be applied in routine analysis of γCD and, because of its simplicity, for determination of cac in aqueous γCD solutions as well as during determination of aggregate formation by the permeation method and determination of γCD concentrations during the phase-solubility studies of drug/γCD inclusion complexes. Two methods for

ACKNOWLEDGMENT

This work was supported by an IWT grant No. 135040.

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RESEARCH ARTICLE – Pharmaceutical NanotechnologyA New Approach for Quantitative Determination of γ-Cyclodextrin in Aqueous Solutions: Application in Aggregate Determinations and Solubility in Hydrocortisone/γ-Cyclodextrin Inclusion Complex

ABSTRACT

Section snippets

INTRODUCTION

Materials

Validation

CONCLUSIONS

ACKNOWLEDGMENT

Adv Colloid Interface Sci

Int J Pharm

J Pharm Sci

J Colloid Interface Sci

Micron

J Pharm Biomed Anal

J Pharm Biomed Anal

J Chromatogr A

J Chro- matogr B

J Pharm Biomed Anal

Int J Pharm

J Chromatogr A

J Chromatogr B

J Colloid Interface Sci

J Chem Thermodyn

Int J Pharm

J Pharm Sci

J Pharm Sci

Int J Pharm

J Chromatogr A

J Control Release

Int J Pharm

Int J Pharm

RESEARCH ARTICLE – Pharmaceutical Nanotechnology
A New Approach for Quantitative Determination of γ-Cyclodextrin in Aqueous Solutions: Application in Aggregate Determinations and Solubility in Hydrocortisone/γ-Cyclodextrin Inclusion Complex