Tetrofosmin Radiopharmaceutical Composition Without Ascorbic Acid
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Solution Overview
Problem
Existing radiopharmaceutical compositions of tetrofosmin face challenges with stability, high radiochemical purity, and bio-distribution, particularly due to the instability of ascorbic acid as a radioprotectant, which requires the use of preservatives and limits shelf-life.
Innovation Solution
A stable radiopharmaceutical composition of tetrofosmin is developed without ascorbic acid, using gentisic acid, para-aminobenzoic acid, or maleic acid as radioprotectants, along with stannous chloride as a reductant and transchelators like gluconic acid, to maintain stability and high radiochemical purity, suitable for industrial production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ascorbic acid is used as radioprotectant, then radiochemical purity is improved, but stability deteriorates due to ascorbic acid instability in solution and UV exposure
Solution Approach 1:
The patent changes the chemical identity of the radioprotectant from ascorbic acid to gentisic acid, para-aminobenzoic acid, or maleic acid. This substitution maintains the radioprotectant function while eliminating the instability problems associated with ascorbic acid, particularly its susceptibility to oxidation and degradation in solution and under UV exposure.
Solution Approach 2:
The patent replaces the unstable ascorbic acid with more stable alternative radioprotectants that have longer shelf-life and maintain their protective function over extended periods, effectively replacing a short-lived unstable component with longer-lived stable alternatives.
2Reliability
If ascorbic acid is used as radioprotectant, then radiochemical purity is improved, but shelf-life deteriorates
Solution Approach 1:
The patent changes the chemical identity of the radioprotectant from ascorbic acid to gentisic acid, para-aminobenzoic acid, or maleic acid. This substitution maintains the radioprotectant function while eliminating the instability problems associated with ascorbic acid, particularly its susceptibility to oxidation and degradation in solution and under UV exposure.
3Stability of the object's composition
If preservatives are added to stabilize composition, then stability is improved, but device complexity deteriorates due to additional components
Solution Approach 1:
The patent removes the need for separate preservative components by selecting radioprotectants (gentisic acid, para-aminobenzoic acid, or maleic acid) that inherently provide both radioprotection and microbial suppression. This extraction of the preservative function simplifies the formulation by eliminating additional components while maintaining stability.
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 composition achieves stability at room temperature, high radiochemical purity, and desired bio-distribution, with a simple and reproducible manufacturing process, suitable for diagnostic use.
Implementation Method 1
stannous chloride as a reductant
Implementation Method 2
gentisic acid, para-aminobenzoic acid, or maleic acid as radioprotectants
Implementation Method 3
transchelators like gluconic acid
Data Source
AI summary
The present invention relates to a stable pharmaceutical composition of tetrofosmin or pharmaceutically acceptable salts thereof. It also relates to a lyophilized non-radioactive kit which upon reconstitution with 99mTc-pertechnetate solution gives a stable 99mTc-tetrofosmin radiopharmaceutical composition. It also provides process for the preparation of said radiopharmaceutical compositions and their use in diagnostic imaging procedures. The compositions provide desirable technical attributes such as stability, purity, high radiochemical purity (RCP) and desired bio-distribution. The composition comprises less than 1% w/w dioxo tetrofosmin (TFS-2) content and less than 1% w/w mono-oxo tetrofosmin content.