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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Amlodipine free base exhibits poor oral absorption due to slow dissolution and low permeability.
• Photosensitive nature of amlodipine poses formulation challenges.
• Enhancing amlodipine's bioavailability is crucial for effective therapeutic outcomes.

Purpose of the Study:

• To formulate and characterize an amorphous solid dispersion (Amlo-SD) of amlodipine free base.
• To improve the oral absorption, dissolution rate, and photostability of amlodipine.
• To evaluate the role of sodium lauryl sulfate (SLS) as an absorption enhancer.

Main Methods:

• Amorphous solid dispersion (Amlo-SD) prepared using spray-drying with dextrin and amlodipine free base (1:10 ratio).
• Sodium lauryl sulfate (SLS) (0.9% w/w) incorporated as an absorption enhancer.
• Characterization included particle size, morphology, amorphous state confirmation, content uniformity, stability, and dissolution studies.
• In vivo oral absorption study in rats was conducted.

Main Results:

• Amlo-SD particles were spherical (12.9 μm average size) with uniform amlodipine content in an amorphous state.
• Amlo-SD demonstrated improved physicochemical and photostability over 6 months at room temperature.
• Significantly faster dissolution of Amlo-SD observed at pH 1.2 and 6.8 compared to amlodipine alone.
• In vivo studies showed a 2.8-fold increase in AUC for Amlo-SD with SLS and a 2.0-fold increase without SLS, indicating enhanced absorption.

Conclusions:

• The developed Amlo-SD system effectively enhances amlodipine's dissolution and oral absorption.
• SLS further potentiates the absorption enhancement, likely via permeability effects.
• Amlo-SD with SLS presents a promising formulation strategy for improving amlodipine's oral bioavailability.