Prediction of protein degradation during vibrating mesh nebulization via a high throughput screening method.
Maintaining the integrity of biopharmaceuticals is a major requirement for successful pulmonary delivery by nebulization. Sparing laborious nebulization tests, this study aimed to demonstrate the feasibility of a high throughput, material saving surrogate method to predict protein stability after nebulization. Detrimental conditions during nebulization with a PARI eFlow® vibrating mesh nebulizer were mimicked by vigorous agitation at elevated temperatures. Comparing the effect of several different excipients on the stability of the protein SM101 after nebulization and after the surrogate method revealed an excellent correlation regarding SM101 aggregation (R(2)=0.97). Design of experiment was used to develop an inhalable formulation of SM101 based entirely on the new surrogate method. Two lead formulation candidates were selected based on their predicted stability profile. The conservation of full SM101 stability and activity after nebulization was confirmed for an AKITA(2) vibrating mesh nebulizer. This study demonstrated that biopharmaceutical formulation development for nebulization is feasible by means of imitating nebulizer related detrimental factors, allowing an accelerated and more economic formulation development.
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University Munich, Munich, Germany. Electronic address: sebastian.hertel@cup.uni-muenchen.de.
Sebastian
S
Hertel
SuppreMol GmbH, Martinsried, Germany.
Thomas
T
Pohl
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University Munich, Munich, Germany.
Wolfgang
W
Friess
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University Munich, Munich, Germany.
Gerhard
G
Winter
D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D005240:Feasibility Studies; D058851:GPI-Linked Proteins / Q000008:administration & dosage / Q000737:chemistry; D057166:High-Throughput Screening Assays; D006358:Hot Temperature; D006801:Humans; D009330:Nebulizers and Vaporizers; D055550:Protein Stability; D059748:Proteolysis; D017452:Receptors, IgG / Q000008:administration & dosage* / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014732:Vibration
D005079:Excipients; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG
AKITA(2); Agitation; Biopharmaceuticals; Design of experiment; FcγRIIB receptor; Formulation development; PARI eFlow®; Protein stability; Screening method; Vibrating mesh nebulization