Vapor-Deposited Oxide Coatings for Stable High-Concentration Polypeptides
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Solution Overview
Problem
Conventional subcutaneous polypeptide formulations face challenges with high solution viscosity, polypeptide aggregation, and instability, necessitating the development of high concentration formulations with improved stability and controlled release profiles.
Innovation Solution
The development of high concentration polypeptide formulations using coated particles with an inorganic oxide coating applied by vapor phase deposition, which includes a silicon oxide and mixed oxide layers, reduces surface charge, increases hydrophilicity, and provides a controlled release profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If high concentration polypeptide formulations are developed to improve patient convenience and compliance, then the injection volume can be reduced, but the solution viscosity increases and polypeptide aggregation and instability occur
Solution Approach 1:
An inorganic oxide coating layer is introduced as an intermediary between the polypeptide particles and the aqueous environment. This coating layer mediates the interaction by providing a protective barrier that prevents direct exposure of polypeptides to conditions causing aggregation and degradation, thereby maintaining stability at high concentrations
Solution Approach 2:
The surface properties of polypeptide particles are modified by changing their chemical composition through the addition of an inorganic oxide coating layer. This parameter change in surface chemistry reduces surface charge and increases hydrophilicity, which prevents aggregation and maintains colloidal stability at high polypeptide concentrations
2Volume of moving object
If high concentration polypeptide formulations are developed, then the injection volume can be reduced, but the solution viscosity increases
Solution Approach 1:
The inorganic oxide coating layer acts as a mediator between polypeptide particles, preventing direct particle-particle interactions that would increase viscosity. The coating provides steric and electrostatic stabilization that maintains fluidity even at high polypeptide concentrations
Solution Approach 2:
The surface charge density of polypeptide particles is reduced through the inorganic oxide coating, which decreases interparticle electrostatic repulsion and attraction. This parameter change in surface charge properties reduces the effective interaction between particles, thereby reducing viscosity at high concentrations
3Quantity of substance
If conventional subcutaneous injection methods are used with high dose polypeptide drugs, then the required dose can be administered, but the injection volume exceeds the acceptable limit of 2 ml
Solution Approach 1:
The formulation achieves ultra-high polypeptide concentrations (≥100 mg/ml) by modifying particle surface properties with an inorganic oxide coating. This parameter change in concentration capability allows the full therapeutic dose to be delivered in a small volume suitable for subcutaneous injection
4Stability of the object's composition
If the coating layer is applied by vapor phase deposition to reduce surface charge and increase hydrophilicity, then polypeptide stability is improved, but the manufacturing process complexity increases
Solution Approach 1:
The coating application process replaces traditional wet chemical methods with vapor phase deposition. This substitution eliminates the need for liquid solvents, multiple washing steps, and extensive drying processes, thereby simplifying the overall manufacturing process despite the advanced deposition technique
Solution Approach 2:
The coating is applied through phase transition of the inorganic oxide precursor from vapor to solid deposit on the polypeptide particles. This phase transition mechanism enables direct formation of the coating layer without intermediate liquid phases, reducing process complexity and eliminating solvent removal steps
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The coated particles result in formulations with reduced viscosity, enhanced stability, and controlled polypeptide release, simplifying the manufacturing process and reducing waste, while maintaining stability and extending the duration of action.
Implementation Method 1
The coating inorganic oxide layer can be applied by vapor phase deposition
Data Source
AI summary
The disclosure is directed at improved polypeptide formulations comprising a coated particle comprising a polypeptide-containing core and a coating layer enclosing the polypeptide-containing core. Methods for manufacturing such a polypeptide formulations are also provided.