DEVELOPMENT OF LIPID NANOPARTICLES COMPRITOL® BASED AS CARRIERS FOR AMIODARONE.

Amiodarone hydrochloride (AMD) is an antiarrhythmic administered for the treatment of ventricular arrhythmias, atrial fibrillation and severe rhythm disturbances (e.g.: supraventricular rhythm disturbances or tachycardia in Wolff-Parkinson-White syndrome). The oral bioavailability of AMD shows many interindividual variations in conventional formulations due to the rapid dealkylation of the molecule to desethylamiodarone (inactive metabolite) and to low water solubility. The oral bioavailability of substances with low solubility and high permeability in the class II biopharmaceutical classification system, such as AMD, can be improved by incorporating them into solid lipid nanoparticles (SLNs). The aim of this study was to investigate the requirements for AMD inclusion in SLNs based on Compritol® 888 ATO which was used as a lipid matrix. This lipid excipient was selected because it leads to the formation of stable small-sized SLNs and it has a high drug loading capacity due to the presence in its structure of variable length chains forming a disordered crystal lattice in whose nets the drug substance gets fixed. SLNs were prepared by homogenization and ultrasonication method using Transcutol as surfactant. To evaluate the effect of probe sonication on SLNs characteristics different trials were taken by varying amplitude and cycle sonication from 20 to 60 % amplitude and 0.5 - 1 cycle. The developed SLNs were characterized in terms of scanning electron microscopy (SEM), mean particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (% EE) and near infrared spectrometry (NIR). The results of the study showed that by increasing the amplitude of sonication, a decrease in the size of SLNs is achieved without significantly influencing the loading capacity of the particles. The resulting SLNs had an average size of 100 nm and an EE of about 63%. Thermal analysis showed compatibility between AMD and Compritol and it also confirmed the formation of SLNs with a uniform morphology and no changes in the crystalline structure of the lipid matrix. To conclude, the AMD-loaded SLNs based on Compritol obtained and characterized in this study are stable and show the morphological features required for studying the biopharmaceutical characteristics. [ABSTRACT FROM AUTHOR]