Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption

Abstract

Objective: To enhance the oral absorption of photosensitive amlodipine free base, which exhibits a slow dissolution rate and low permeability characteristics, an amorphous solid dispersion system was formulated and characterized.

Material and methods: The solid dispersion was prepared by dispersing the amlodipine free base in excess dextrin (1:10 by weight) using a spray-drying technique in the presence of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin-based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of formulation, characterization and in vivo absorption study, as well as the spray-drying process was also optimized.

Results and discussion: The Amlo-SD particles were spherical with a smooth surface and an average particle size of 12.9 μm. Amlodipine was dispersed in an amorphous state and its content remained uniform in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at room temperature for 6 months and the photostability was considerably improved. The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2 and 6.8. Amlo-SD produced significantly higher plasma concentrations of amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided 2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be attributed to a permeability enhancement effect by SLS.

Conclusion: The Amlo-SD with SLS system is a potential formulation option for amlodipine.

Keywords::

• Amlodipine
• dextrin
• dissolution rate
• oral absorption
• permeability
• solid dispersion