Development of a Carvedilol Oral Liquid Formulation for Paediatric Use

Area of Science:

• Pharmaceutical Sciences
• Pediatric Pharmacology
• Drug Formulation

Background:

• Carvedilol (CARV) is an essential beta-blocker for pediatric cardiovascular diseases, but its poor aqueous solubility limits administration.
• Current practice involves extemporaneous preparation of liquid CARV formulations from solid tablets, posing challenges for accurate dosing in children.

Purpose of the Study:

• To enhance the aqueous solubility of carvedilol (CARV) and develop a stable, pediatric-suitable oral solution.
• To assess the chemical, physical, and microbiological stability of the developed CARV solution.
• To optimize CARV solution preparation using Design of Experiments (DoE).

Main Methods:

• Solubility and preliminary stability of CARV were evaluated in various pH media.
• Malic acid was investigated as a solubility enhancer for CARV.
• Chemical, physical, and microbiological stability of a 1 mg/mL CARV-malic acid solution were assessed.
• Design of Experiments (DoE) was employed to optimize preparation parameters.

Main Results:

• Malic acid significantly improved CARV aqueous solubility, yielding satisfactory results.
• A 1 mg/mL CARV-malic acid solution demonstrated stability for 12 months at 25°C and 30°C, and 6 months at 40°C.
• DoE provided an equation to associate malic acid and CARV concentrations, and methylparaben was found unnecessary for short-term stability.

Conclusions:

• A stable aqueous oral solution of carvedilol (CARV) suitable for pediatric use was successfully developed.
• The CARV-malic acid solution offers a reliable and stable formulation for up to 12 months, addressing a critical need in pediatric cardiovascular care.