Autoinjector optimization through cavitation response and severity minimization
[Display omitted] •Multi-objective auto-injector optimization undertaken to find configurations with minimal cavitation response.•Constraint meeting configurations must also needle displacement and injection time for wide range of viscosity.•Deep Neural Network Surrogate model built to quickly find...
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Veröffentlicht in: | International journal of pharmaceutics 2024-12, Vol.667 (Pt A), p.124888, Article 124888 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | [Display omitted]
•Multi-objective auto-injector optimization undertaken to find configurations with minimal cavitation response.•Constraint meeting configurations must also needle displacement and injection time for wide range of viscosity.•Deep Neural Network Surrogate model built to quickly find constraint-meeting autoinjectors configurations.•Constraint-meeting autoinjectors built for high-viscosity solutions also met constraints at low-viscosities.
Abrupt acceleration of the syringe of an autoinjector (AI) upon rod-plunger impact may induce undesired severe cavitation events and impose extraneous stresses upon the device, leading to device failure. Cavitation results from a rapid and significant pressure drop in a liquid, leading to the formation and growth of small vapor-filled cavities. Upon collapse, these cavities generate an intense shock wave that may lead to protein aggregation and device container damage and shatter. Since the maximum acceleration of the syringe depends upon the operating conditions of the AI, the severity of cavitation will likewise depend on the operating conditions of the AI. Likewise, injection time and ensuring proper needle displacement before drug release also depend on operating conditions, making optimization of the autoinjector a multiobjective optimization problem.
Therefore, in this study, optimization of an autoinjector to limit cavitation severity is pursued via an experimentally validated computational model for cavitation in spring-driven autoinjectors. Our goal is to locate AI design configurations that balance maximizing device performance and patient comfort and minimizing the risks of device damage and severe cavitation upon actuation.
Relevant parameters of interest are the drive spring force, air gap height, solution viscosity, friction between the rod and spring, frictional force on the plunger, rates of change of frictional force on the plunger, elasticity of plunger, viscosity of the plunger, and initial displacement between the plunger and the driving rod. The kinematics of the syringe barrel, needle displacement (travel distance) at the start of drug delivery, and injection time are gathered using an experimentally validated autoinjector kinematics model. At the same time, cavitation bubble dynamics are resolved using an experimentally validated cavitation model that takes the temporal displacement of the syringe and temporal air gap pressure as inputs.
We use our experimentally validated models to e |
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ISSN: | 0378-5173 1873-3476 1873-3476 |
DOI: | 10.1016/j.ijpharm.2024.124888 |