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

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Digoxin, a widely used cardiac glycoside, exhibits poor water solubility, limiting its oral bioavailability.
• Conventional oral dosage forms of digoxin may present challenges in dissolution rate and absorption.
• Developing improved solid dosage forms is crucial for enhancing therapeutic efficacy and patient compliance.

Purpose of the Study:

• To develop a novel, rapidly absorbed oral dosage form of digoxin using spray-drying technology.
• To evaluate the in vitro dissolution and in vivo absorption characteristics of the developed digoxin dry elixir.
• To compare the performance of the digoxin dry elixir with conventional digoxin elixir and digoxin powder.

Main Methods:

• Development of digoxin dry elixir via spray-drying technique using digoxin, dextrin, and sodium lauryl sulphate in an ethanol-water mixture.
• Characterization of digoxin dry elixir using scanning electron microscopy and laser particle size analysis.
• In vitro dissolution studies in distilled water at 37°C and in vivo pharmacokinetic studies in animals comparing dry elixir, elixir, and powder formulations.

Main Results:

• The digoxin dry elixir exhibited a spherical shape with a mean particle size of approximately 13 microns.
• In vitro dissolution studies showed complete dissolution of digoxin from the dry elixir within 2 minutes, over 100-fold faster than digoxin powder.
• In vivo studies demonstrated a 3.8-fold increase in maximal plasma concentration (Cmax) and a 5.5-fold increase in area under the curve (AUC0-6h) for the dry elixir compared to powder, with a reduced Cmax compared to digoxin elixir.

Conclusions:

• The spray-dried digoxin dry elixir is a promising solid dosage form that significantly improves the dissolution rate and bioavailability of poorly soluble digoxin compared to digoxin powder.
• The dry elixir formulation offers comparable bioavailability to liquid digoxin elixir but with a potentially reduced Cmax, suggesting a possible reduction in associated side effects.
• This novel dosage form holds potential for enhancing the therapeutic outcomes of oral digitalis glycoside therapy.