Erythritol-based dry powder of glucagon for pulmonary administration.
Glucagon, a key regulatory element of glycogen metabolism, is known to be effective in the clinical treatment of hypoglycemia and the maintenance of normal circulating glucose levels in patients with total pancreatectomy, however the clinical use of this gut hormone has been restricted to parenteral administration. In this investigation, we prepared dry powder dosage forms of glucagon, which were formulated by mixing micronized glucagon particles and excipients with larger carrier particles. To achieve alveolar deposition for subsequent systemic absorption, a dry powder inhalant (DPI) of glucagon was size-reduced to a mass median diameter between 1 and 6 microm, as measured by laser diffraction analysis. The use of erythritol as both excipient and carrier in DPI of glucagon resulted in high and reproducible flowability and dispersibility of the powder mixtures, and therefore it provided a low dosing of the active substances. Distinct transpulmonary absorption of glucagon was confirmed after intratracheal administration of the glucagon dry powder to anesthetized rats, as evidenced by the increase in the blood glucagon and blood sugar levels. These results suggested the usefulness of an erythritol-based powder form of glucagon for systemic administration.
Endo
Kosuke
K
Pharmaceutical Division, Ito Life Sciences Inc., 1-2-1 Kubogaoka, Moriya, Ibaraki 302-0104, Japan.
Amikawa
Satoko
S
Matsumoto
Asami
A
Sahashi
Norio
N
Onoue
Satomi
S
D000280:Administration, Inhalation; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004896:Erythritol / Q000008:administration & dosage* / Q000737:chemistry; D005934:Glucagon / Q000008:administration & dosage* / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D011208:Powders; D005934:Glucagon; D004896:Erythritol