Validation of an HPLC Analytical Method for the Quantitative/Qualitative Determination of Fluticasone Propionate in Inhalation Particles on Several Matrices.

André R Sá Couto

doi:10.3797/scipharm.1404-11

Abstract

Fluticasone propionate is a highly potent corticosteroid used to treat asthma and allergic rhinitis. It is a very effective drug, but has the inconvenient factor of being insoluble in water. Cyclodextrins were used to improve this limitation because of their ability to form inclusion complexes with guest drug molecules as well as increase the stability and bioavailability of the drugs. A rapid and simple HPLC method was developed to detect and quantify fluticasone propionate in inhalation particles on several matrices. Liquid chromatography with a UV detector at a wavelength of 236 nm, using a C18 column, was employed in this study. Isocratic elution was employed using a mixture of acetonitrile and water (60:40, v/v). The analytical method validation was performed in accordance with ICH guidelines, which included selectivity, range, linearity, accuracy, detection limit, quantitation limit, precision, robustness, and stability of solutions. This method showed to be selective and specific. Acceptable assay precision and accuracy (100 ± 5.0%) were obtained at 50– 150% of the analytical concentration of fluticasone propionate at the target concentration of 0.060 mg/mL, and good linearity (0.9958) was achieved over a range of 0.03 to 0.09 mg/mL for fluticasone propionate. The proposed HPLC method proved to be reliable. The validation and application of this method can be adopted for determining the fluticasone propionate in: assays, impingers and impactors, diffusion cells, dissolutions, and other tests. In addition, this method can be adapted and used in the pharmaceutical industry for routine analysis.

Highlights

Chronic respiratory diseases, which include asthma and chronic obstructive pulmonary diseases, comprise a major cause of death and disability for all age groups and regions in the world [1]
In the last estimates of the World Health Organization, 235 million people had asthma, 64 million suffered from chronic obstructive pulmonary disease, and a few other million had allergic rhinitis or other often underdiagnosed respiratory diseases [2]. The treatment of these diseases consists of treatment with inhalation drugs formulated to be used as a nasal spray, dry powder inhaler, metered-dose inhaler, or as a nebulizer [1]
Fluticasone propionate (FP), a second-generation trifluorinated glucocorticosteroid based on the androstane nucleus, is a highly potent drug and one of the most used corticosteroids to treat asthma and allergic rhinitis [1]

Summary

Introduction

Chronic respiratory diseases, which include asthma and chronic obstructive pulmonary diseases, comprise a major cause of death and disability for all age groups and regions in the world [1]. In the last estimates of the World Health Organization, 235 million people had asthma, 64 million suffered from chronic obstructive pulmonary disease, and a few other million had allergic rhinitis or other often underdiagnosed respiratory diseases [2]. Even though some commercial formulations of inhaled microparticles can only deliver a low percentage (10–20%) of their labelled dose in the interest area of the lungs [3], these devices and their formulations are still effective, non-invasive, and convenient ways to provide a pulmonary administration of small molecule drugs and biopharmaceuticals [4]. Fluticasone propionate (FP), a second-generation trifluorinated glucocorticosteroid based on the androstane nucleus, is a highly potent drug and one of the most used corticosteroids to treat asthma (inhalation) and allergic rhinitis (intranasally) [1]. In order to be pharmacologically active, drugs should be lipophilic to permeate the biological membrane (through passive diffusion) and at the same time must have some aqueous solubility [7]

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Conclusion