Amiodarone hydrochloride: enhancement of solubility and dissolution rate by solid dispersion technique

Abstract

Amiodarone HCl is an antiarrhythmic agent, which has low aqueous solubility and presents absorption problems. This study aimed to develop inclusion complexes containing hydrophilic carriers PEG 1500, 4000 and 6000 by fusion and kneading methods in order to evaluate the increase in solubility and dissolution rate of amiodarone HCl. The solid dispersion and physical mixtures were characterized by X-ray diffraction, FT-IR spectra, water solubility and dissolution profiles. Both methods and carriers increased the solubility of drug, however PEG 6000 enhanced the drug solubility in solid dispersion better than other carriers. Different media were evaluated for the solubility study, including distilled water, acid buffer pH 1.2, acetate buffer pH 4.5 and phosphate buffer pH 6.8 at 37 ºC. Based on the evaluation of the results obtained in the study phase solubility carriers PEG 4000 and PEG 6000 were selected for the preparation of the physical mixture and solid dispersion. All formulations were prepared at drug-carrier ratios of 1:1 to 1:10(w/w). The results of in vitro release studies indicated that the solid dispersion technique by fusion method in proportion of 1:10 (w/w) increased significantly the dissolution rate of the drug. X-ray diffraction studies showed reduced drug crystallinity in the solid dispersions. FT-IR demonstrated interactions between the drug and polymers.

Study on the interaction between erythrosine B and the cardiac drug amiodarone using fluorescence, scattering, and absorbance spectra and their analytical application

“…An exact weight (20 mg) of AMD powder was prepped by sonicating the weighed AMD powder with about 30 mL of methanol in a volumetric flask [36,37]. Then, the volume was completed with water to 100 mL.…”

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

“…The samples were covered to avoid solvent loss and then shaken at 140 rpm in an orbital shaking incubator (Novatecnica ® , NT712) for 24 hours. After equilibrium, samples were centrifuged at 4000 rpm for 10 minutes, and then the concentration of AMH in supernatant liquid was determined by HPLC (Rubim et al, 2015).…”

Nanocrytals-Mediated Oral Drug Delivery: Enhanced Bioavailability of Amiodarone

“…The term “low solubility” is applied when the maximum concentration of a drug dissolved in water is <10 mg/mL [ 2 ]. Pharmaceutical scientists are considering various techniques, such as, micronization, self-emulsification, salt formation, co-crystallization, cyclodextrin inclusions, solid dispersions, solid lipid nanoparticles and nanocrystallization, to enhance the dissolution and bioavailability of the poorly soluble drugs [ 3 ]. Most of these approaches use an excessive number of excipients with a resultant low drug loading capacity, making them suitable only for drugs with a low dose requirement [ 4 , 5 ].…”