Insulin microcrystal suspension as a long-acting formulation for pulmonary delivery

Jai Hyun Kwon, Byung Ha Lee, Jae Jeong Lee, Chan Wha Kim

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Pulmonary delivery provides the most promising non-parenteral route of insulin administration. Insulin was used as a model protein to demonstrate the feasibility of using protein crystals for the pulmonary delivery of a sustained-release protein drug formulation. Insulin microcrystals with a mean diameter of 3 μm were prepared using a seed zone method. The yield of crystallization was very high (95.8±0.97%), and the microcrystals were recovered with high efficiency (>98%) by centrifugation. Morphological examination using scanning electron microphotography showed the microcrystals to be of a homogeneous rhombohedral shape, with some rhombus forms, without aggregates. After the administration of 32 U/kg of the microcrystal suspension to STZ-induced diabetic SD rats by intratracheal instillation, the blood glucose levels were reduced and hypoglycemia was prolonged over 13 h, as compared to the insulin solution. The percent minimum reductions of the blood glucose concentration (% MRBG) produced by the microcrystal suspension and insulin solution reached 36.5 and 37.2%, respectively, of the initial level, and the percent total reductions in blood glucose (% TRBG13h) were 34.4 and 25.0%, respectively. In the case of inhalation using a sieve-type ultrasonic nebulizer, the % MRBG produced by the microcrystal suspension and insulin solution were 21.7 and 26.3%, respectively, of the initial level, and the % TRBG13h were 66.7 and 58.4%, respectively. However, the hypoglycemic effects of the microcrystal suspension were prolonged over 7 h, which compares favorably with the insulin solution (P<0.05 by unpaired t-test). These results could be attributed to the sustained-release of insulin from the microcrystals, which were deposited widely throughout the entire lung.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume22
Issue number2-3
DOIs
Publication statusPublished - 2004 Jun

Keywords

  • Diabetes
  • Inhalation
  • Insulin
  • Long-acting
  • Microcrystal

ASJC Scopus subject areas

  • Pharmaceutical Science

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