Formulation and in vitro evaluation of highly dispersive insulin dry powder formulations for lung administration

• Published in: European journal of pharmaceutics and biopharmaceutics 2010-11, Vol.76 (3), p.454-463
• Main Authors: Depreter, Flore, Amighi, Karim
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Biological and medical sciences; Cholesterol - chemistry; Drug Stability; Dry powder inhaler (DPI); Dry Powder Inhalers; Excipients; General pharmacology; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacokinetics; Insulin; Insulin - administration & dosage; Insulin - chemistry; Insulin - pharmacokinetics; Lipids; Lung - metabolism; Medical sciences; Microparticles; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phospholipids - chemistry; Pulmonary delivery; Spray-drying
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.08.005

The aim of this work was to develop highly dispersible and dry formulations of insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation (HPH) and spray-drying. Several formulations were evaluated, including formulations spray-dried without excipients and formulations coated with lipids. The resulting powders exhibited a size and shape suitable for the deep lung deposition of drugs. Good aerodynamic features were obtained, with fine particle fractions between 46% and 63% vs. 11% for raw insulin powder. The aim of this work was to develop highly dispersible and dry formulations of insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation (HPH) and spray-drying. Several formulations were evaluated, including formulations spray-dried without excipients and formulations coated with lipids. A physiological lipid composition based on a mixture of cholesterol and phospholipids was used to form the coating film around micronised drug particles. The production technique and excipients were chosen in order to limit the degradation of the active ingredient. The resulting powders exhibited a size and shape suitable for the deep lung deposition of drugs, and good aerodynamic features were obtained for the different formulations tested, with fine particle fractions between 46% and 63% vs. 11% for raw insulin powder. The presence of a lipid coating of up to 30% (w/w) did not significantly affect the aerodynamic behaviour, and the coated formulations also exhibited a decreased residual moisture content of between 2.3% and 3.7% vs. 4.8% for raw insulin, which should improve the long-term stability of the protein formulations. No degradation of the insulin molecule occurred during the HPH/spray-drying process, as it was shown using an HPLC method (insulin content between 98.4% and 100.5%), and the content in high molecular weight proteins, assessed using a gel filtration method, stayed below 0.4%.