Ready-to-Use Aqueous Ganciclovir Compositions at Lower Injection pH
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Solution Overview
Problem
Current lyophilized ganciclovir products are costly to manufacture, require aseptic reconstitution, and have a high pH that causes injection site reactions in some patients.
Innovation Solution
Development of stable, injectable, and ready-to-administer aqueous ganciclovir compositions with a ganciclovir base at 2.0 mg/ml, isotonic agents, and pH adjusters to achieve a pH of 5.5 to 8, which are terminally sterilized and free of particulate matter.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If lyophilized powder product is used, then ganciclovir can be provided as a stable formulation, but manufacturing cost increases and requires reconstitution
Solution Approach 1:
The patent changes the physical state parameter from lyophilized powder to liquid formulation, and adjusts pH from 11 to 5.5-8.0, transforming the product into a ready-to-administer liquid that eliminates reconstitution steps while reducing manufacturing complexity and cost
2Stability of the object's composition
If lyophilized powder product is used, then ganciclovir can be provided as a stable formulation, but reconstitution requires aseptic technique which could lead to sterility compromise
Solution Approach 1:
The patent performs sterility assurance during the final filling and sealing process rather than requiring aseptic technique at the point of use. The liquid formulation is filled into containers and sealed under controlled conditions, with terminal sterilization applied to the finished product, eliminating the need for healthcare providers to perform aseptic reconstitution
3Quantity of substance
If ganciclovir sodium salt is used, then solubility is improved, but pH becomes 11 which causes injection site reactions
Solution Approach 1:
The patent changes the pH parameter from 11 to 5.5-8.0 by using ganciclovir base instead of ganciclovir sodium salt and adding pH adjusters (hydrochloric acid or sulfuric acid), thereby maintaining adequate solubility while eliminating injection site reactions caused by high pH
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 compositions provide stability, ease of administration, and reduced pH, minimizing manufacturing costs and patient discomfort, while maintaining solubility and sterility.
Implementation Method 1
a pH adjuster to adjust the pH of the composition from about 5.5 to about 8
Implementation Method 2
either sodium chloride or dextrose as a tonicity agent at a concentration sufficient to make the composition isotonic
Implementation Method 3
the composition is terminally sterilized
Data Source
AI summary
Gancyclovir formulations that are ready-to-use, substantially particulate free, and stable upon storage are disclosed. Methods of manufacture and administration of such compositions are also provided.