Nasal glucagon delivery using microcrystalline cellulose in healthy volunteers.
We developed an intranasal powder form of glucagon to improve metabolic status and fatty liver in patients with pancreatectomy. Microcrystalline cellulose, which is commonly used in commercial preparations for allergic rhinitis was used as an absorption enhancer. We compared the intranasal powder form with some spray solutions of glucagon with regard to glucagon absorption, concentration of blood glucose, stability and nasal irritation. The absorption of glucagon from the spray solution including 1.5% sodium glycocholate or 1% sodium caprate was 1.3- and 2.6-fold higher than that from the powder form mixed with microcrystalline cellulose at a ratio of 1:69, respectively. The C(max) values of plasma glucose were 2.18, 3.39 and 1.56 mmol l(-1) in the spray solutions including sodium glycocholate and sodium caprate and in the powder form, respectively. However, glucagon in spray solutions was unstable, but that in the powder form was stable at 5 and 25 degrees C for at least 84 days. The spray solution caused strong irritation, but the powder form did not. These results suggested usefulness of the powder form of glucagon for treatment of pancreatectomized patients.
Teshima
D
D
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, 3-1-1, Higashi-ku, Maidashi, Fukuoka 812-8582, Japan. dteshima@st.hosp.kyushu-u.ac.jp
Yamauchi
A
A
Makino
K
K
Kataoka
Y
Y
Arita
Y
Y
Nawata
H
H
Oishi
R
R
D000281:Administration, Intranasal; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D002482:Cellulose / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000008:administration & dosage; D005934:Glucagon / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D011208:Powders; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000097:blood
D001786:Blood Glucose; D005079:Excipients; D011208:Powders; D011500:Protein Synthesis Inhibitors; D002482:Cellulose; D005934:Glucagon; C109691:microcrystalline cellulose