Inclusion complex of amiodarone hydrochloride with cyclodextrins: preparation, characterization and dissolution rate evaluation

Alexandre Machado Rubim,Jaqueline Bandeira Rubenick,Clarice Madalena Bueno Rolim,Luciane Varini Laporta,Marcela Maurer

doi:10.1590/s2175-97902017000216083

Alexandre Machado Rubim, Jaqueline Bandeira Rubenick + Show 3 more

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https://doi.org/10.1590/s2175-97902017000216083

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Abstract

This study aimed to improve the water solubility of amiodarone hydrochloride (AMH) via inclusion complexes with β-cyclodextrin, methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Inclusion complexes were developed by physical mixture, coevaporation, spray-drying and freeze-drying. Solid state analysis was performed using X-ray powder diffraction, differential scanning calorimetry and scanning electronic microscopy. Thermodynamic studies demonstrate that the inclusion complexes of drug into different cyclodextrins were an exothermic process that occurred spontaneously. Water solubility and drug dissolution rates were significantly increased after the formation of inclusion complexes with the cyclodextrins evaluated in relation to the physical mixture and pure drug. The present study provides useful information for the potential application of complexation with amiodarone HCl. This may be a good strategy for the development of solid pharmaceutical dosage forms.

Highlights

Amiodarone hydrochloride (AMH), chemically known as (2-butylbenzofuran-3-yl)[4-[2-(diethylamino) ethoxy]-3,5-diiodophenyl]methanone hydrochloride, used for the treatment of both supraventricular and ventricular arrhythmias (Lafuente-Lafuente et al, 2009)
The complex formed between AMH and CDs presented an enhanced solubility and dissolution rate for all complexes formed other than either physical mixture or pure drug
AMH solubility linearly increases with increasing concentrations of CDs of both temperatures indicating an AL-type diagram over the entire concentration range evaluated

Summary

Introduction

Amiodarone hydrochloride (AMH), chemically known as (2-butylbenzofuran-3-yl)[4-[2-(diethylamino) ethoxy]-3,5-diiodophenyl]methanone hydrochloride, used for the treatment of both supraventricular and ventricular arrhythmias (Lafuente-Lafuente et al, 2009). According to the Biopharmaceutical Classification System (BCS), AMH is a class II. Class II drugs are those with low solubilities and high permeabilities (Amidon et al, 1995; Benet, 2005). For drugs with low gastrointestinal solubility and high permeability, dissolution in physiological fluids is the limiting step for oral bioavailability. These properties are a challenge for the pharmaceutical industry, since more than 70% of the new drugs have low solubility showing

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