Microencapsulation of chlorthalidone by spray-drying of double emulsion and melt granulation coating

ABSTRACT

Chlorthalidone (CH) is indicated in the management of hypertension either alone or in combination with other antihypertensive drugs, but it displays poor solubility and stability limiting its use in the development of new pharmaceutical alternatives. Spray-drying of double emulsions (SDE) and melt granulation coating (MGC) technologies were used for enhancing the stability of CH by using Eudragit® L30D-55 (EUD), Opadry® II (OPA), or Kollicoat® IR (KIR) as wall materials. SDE and MGC microcapsules containing CH were evaluated for particle size, morphology, release profiles, accelerated storage, and thermo-oxidative stability. Both types of microcapsules showed higher solubility (>80% in 20 min), lower degradation (<2%) under accelerated storage condition, and lower thermo-oxidative degradation than pure CH. However, SDE microcapsules showed smaller particle sizes (<16 µm) than MGC microcapsules (>700 µm), which widens the opportunity of incorporating microcapsules to dosage forms requiring different particle sizes for achieving their functionality.

KEYWORDS:

• Chlorthalidone
• double emulsions
• melt granulation coating
• microcapsules
• spray-drying
• stability