A novel pure insulin spray-dried powder for DPI product (Ins_SD) was studied with respect to physico-chemical stability, in vitro respirability, bioavailability, activity and tolerability. Ins_SD powder exhibited a very high in vitro respirability, independently of the DPI product preparation (manual or semi-automatic). Physico-chemical characteristics of Ins_SD powder remained within the pharmacopoeia limits during 6 months of storage at room temperature. PK/PD profiles were measured in rats that received the pulmonary powders by intratracheal insufflation and compared with Afrezza inhalation insulin. Due to the low drug powder mass to deliver, both insulin powders were diluted with mannitol. Insulin from Ins_SD was promptly absorbed (tmax 15 min and Cmaxx4.9 ± 1.5 mU/ml). Afrezza had a slower absorption (tmax 30 min and Cmax of 1.8 ± 0.37 mU/ml). After glucose injection, Ins_SD determined a rapid reduction of glucose level, similar to Afrezza. As reference, insulin subcutaneous injection showed a long-lasting hypoglycemic effect due to the slow absorption that prolonged insulin plasma level. In summary, Ins_SD product is suitable for post-prandial glucose control, providing a convenient and compliant product, in particular in the event of using a disposable device. Albeit the product has to be stored in fridge, its stability at room temperature allows the diabetic individual to carry the daily dose in normal conditions.

Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats / Quarta, Eride; Chierici, Veronica; Flammini, Lisa; Tognolini, Massimiliano; Barocelli, Elisabetta; Cantoni, Anna Maria; Dujovny, Gabriela; Ecenarro Probst, Susana; Sonvico, Fabio; Colombo, Gaia; Rossi, Alessandra; Bettini, Ruggero; Colombo, Paolo; Buttini, Francesca. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - 323:(2020), pp. 412-420. [10.1016/j.jconrel.2020.04.015]

Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats

Quarta, Eride
Investigation
;
Chierici, Veronica
Investigation
;
Flammini, Lisa
Investigation
;
Tognolini, Massimiliano
Data Curation
;
Barocelli, Elisabetta;Cantoni, Anna Maria
Investigation
;
Sonvico, Fabio
Data Curation
;
Colombo, Gaia
Writing – Review & Editing
;
Rossi, Alessandra
Writing – Review & Editing
;
Bettini, Ruggero
Conceptualization
;
Colombo, Paolo
Conceptualization
;
Buttini, Francesca
Supervision
2020-01-01

Abstract

A novel pure insulin spray-dried powder for DPI product (Ins_SD) was studied with respect to physico-chemical stability, in vitro respirability, bioavailability, activity and tolerability. Ins_SD powder exhibited a very high in vitro respirability, independently of the DPI product preparation (manual or semi-automatic). Physico-chemical characteristics of Ins_SD powder remained within the pharmacopoeia limits during 6 months of storage at room temperature. PK/PD profiles were measured in rats that received the pulmonary powders by intratracheal insufflation and compared with Afrezza inhalation insulin. Due to the low drug powder mass to deliver, both insulin powders were diluted with mannitol. Insulin from Ins_SD was promptly absorbed (tmax 15 min and Cmaxx4.9 ± 1.5 mU/ml). Afrezza had a slower absorption (tmax 30 min and Cmax of 1.8 ± 0.37 mU/ml). After glucose injection, Ins_SD determined a rapid reduction of glucose level, similar to Afrezza. As reference, insulin subcutaneous injection showed a long-lasting hypoglycemic effect due to the slow absorption that prolonged insulin plasma level. In summary, Ins_SD product is suitable for post-prandial glucose control, providing a convenient and compliant product, in particular in the event of using a disposable device. Albeit the product has to be stored in fridge, its stability at room temperature allows the diabetic individual to carry the daily dose in normal conditions.
2020
Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats / Quarta, Eride; Chierici, Veronica; Flammini, Lisa; Tognolini, Massimiliano; Barocelli, Elisabetta; Cantoni, Anna Maria; Dujovny, Gabriela; Ecenarro Probst, Susana; Sonvico, Fabio; Colombo, Gaia; Rossi, Alessandra; Bettini, Ruggero; Colombo, Paolo; Buttini, Francesca. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - 323:(2020), pp. 412-420. [10.1016/j.jconrel.2020.04.015]
File in questo prodotto:
File Dimensione Formato  
JCR-S-20-00083.pdf

accesso aperto

Tipologia: Documento in Pre-print
Licenza: Creative commons
Dimensione 2.7 MB
Formato Adobe PDF
2.7 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2877738
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 21
social impact