Dry Solid Vaccine Formulations with Excipients for Thermal Stability
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Solution Overview
Problem
Current influenza and measles vaccines face challenges in stability and distribution due to their liquid formulations, which are sensitive to temperature and handling, leading to significant wastage and difficulties in mass vaccination efforts.
Innovation Solution
Development of dry solid formulations of vaccines, specifically using subunit inactivated influenza or measles antigens combined with excipients like sucrose and arginine, which improve stability and can be administered through dissolvable microneedles or coated microneedles, allowing for improved storage and transportation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid formulations are used for influenza and measles vaccines, then the vaccines can be easily administered, but they require strict temperature control (2-8°C) and are sensitive to handling, leading to significant wastage
Solution Approach 1:
The patent transforms the vaccine formulation from liquid to dry solid state, fundamentally changing the physical parameter of the vaccine. This phase change eliminates the need for cold chain storage while preserving vaccine stability and efficacy, allowing storage at ambient temperatures without refrigeration
Solution Approach 2:
The patent uses composite materials by combining vaccine antigens with protective excipients such as sugars (sucrose, trehalose), amino acids (arginine, glycine), and polymers. These composite dry formulations maintain vaccine stability through the protective matrix, enabling both ease of administration and improved storage reliability
2Reliability
If freeze drying is used to produce dry vaccine formulations, then storage stability is improved, but the virus is exposed to low temperature, adsorption to ice crystal surface, and dehydration stress
Solution Approach 1:
The patent applies preliminary protective action by incorporating stabilizing excipients (sugars, amino acids, polymers) into the vaccine formulation before drying. These excipients form a protective matrix that shields the virus from thermal and mechanical stresses during the freeze drying process, preventing adsorption to ice crystals and reducing dehydration damage
Solution Approach 2:
The patent modifies the drying parameters by using controlled freeze drying conditions with optimized freezing rates and drying temperatures. This parameter optimization minimizes ice crystal formation and associated mechanical stress on viral particles while maintaining storage stability
3Productivity
If spray drying is used to stabilize thermally labile APIs, then high volume throughput is achieved, but excessive shear stress, surface tension, and pressure are applied during atomization
Solution Approach 1:
The patent optimizes spray drying parameters including atomization pressure, droplet size distribution, and drying temperature. By controlling these parameters, the process achieves high throughput while minimizing shear stress and pressure exposure to thermally labile vaccine antigens, preserving their bioactivity
Data Source
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AI summary
Formulations and methods are provided for stabilizing antigens in dry solid vaccines. One aspect relates to dry solid formulations of influenza vaccines including one or more excipients identified as imparting stability to influenza antigens. Another aspect relates to dry solid formulations of measles vaccines including one or more excipients identified as imparting stability to a measles antigen. The formulations may be in a form suitable for reconstitution in a physiologically acceptable liquid vehicle to form an injectable solution or suspension for administration to a patient or in the form of dissolvable microneedles or coated microneedles.