Development of digoxin dry elixir as a novel dosage form using a spray-drying technique

Abstract

A rapidly absorbed new novel oral dosage form for digoxin termed ‘digoxin dry elixir’ was developed by the spray-drying technique. Digoxin, dextrin and sodium lauryl sulphate were dissolved in a ethanol-water mixture (20:25 w/w) and therefore spray-dried to form the digoxin dry elixir. According to scanning electron micrographs, digoxin dry elixir is spherical in shape with a smooth surface. The geometric mean diameter of dry elixir determined by laser particle size analysis was about 13 pm. The appearance and flow properties were almost unchanged and about 10% of ethanol contents in the dry elixir decreased during 180 days in a sealed bottle at room temperature. Comparative studies on the in vitro dissolution and in vivo absorption of digoxin in the form of digoxin dry elixir, digoxin elixir and digoxin powder were carried out. Digoxin in the dry elixirs was completely dissolved within 2 min. On the other hand, only about 87% of digoxin powder dissolved in 60min. The initial dissolution rates of digoxin in the dry elixirs markedly increased in distilled water at 37°C, which were over 100 fold higher than that of digoxin powder alone. The maximal plasma concentration of digoxin (C_max) and area under the digoxin concentration-time curve from zero to 6h (AUC_0–6h) after the oral administration of digoxin dry elixir were almost 3.8 and 5.5 fold increased compared to digoxin powder alone. No significant difference of AUC_0–6h between dry elixir and elixir was observed, but the C_max of digoxin in the form of dry elixir was significantly reduced compared to the digoxin elixir (0.57 versus 0.83). Digoxin dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble digoxin compared to digoxin powder alone. It also indicates that dry elixir might reduce the side effects in oral digitalis glycoside therapy compared to the digoxin elixir due to the reduction of C_max.

Key Words:

• Digoxin
• dry elixir
• ethanol
• dextrin
• spray-drying
• bioavailability