Azithromycin Premix Formulation for Sterile IV Stability
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Solution Overview
Problem
There is no single, sterile, stable, and ready-to-use IV infusion system available for azithromycin, requiring two aseptic preparation steps and potential degradation due to terminal sterilization.
Innovation Solution
An aseptically prepared pharmaceutically acceptable azithromycin premix formulation with a pH of 5.5 to 7.5, containing azithromycin, a buffering agent, and optionally a tonicity adjusting agent, is filled into a container without terminal sterilization, maintaining stability for up to 24 months at refrigerated temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If terminal sterilization is used to ensure sterility, then sterilization is achieved, but azithromycin degradation occurs and stability is compromised
Solution Approach 1:
The formulation is prepared aseptically before filling into the container, eliminating the need for terminal sterilization. The pH is adjusted to 5.5-7.5 and buffering agents are added in advance to maintain stability during storage without requiring post-preparation sterilization heat treatment that would degrade the azithromycin.
2Stability of the object's composition
If lyophilized powder requiring reconstitution is used, then storage stability is improved, but preparation complexity and potential for error increase
Solution Approach 1:
The invention combines the drug substance with buffering agents and tonicity adjusting agents in a single aseptically prepared formulation that is stable in liquid form. This merges multiple components into one ready-to-use product that maintains stability without requiring reconstitution, eliminating the two-step preparation process while preserving storage stability through pH control and aseptic manufacturing.
3Reliability
If multiple aseptic preparation steps are required, then sterility can be maintained, but preparation time and risk of contamination increase
Solution Approach 1:
The complete formulation including azithromycin, buffering agents, and tonicity adjusting agents is prepared aseptically in advance and filled into the final container in a single aseptic operation. This preliminary aseptic preparation eliminates the need for multiple subsequent aseptic steps (reconstitution and dilution), reducing both time and contamination risk while maintaining sterility.
4Device complexity
If pH is not controlled within optimal range, then formulation simplicity is maintained, but stability and impurity formation are compromised
Solution Approach 1:
The pH of the formulation is controlled within the optimal range of 5.5-7.5 through the addition of buffering agents. This parameter change ensures azithromycin stability, prevents degradation, and minimizes impurity formation during storage, while the buffering agents used are pharmaceutically acceptable and do not significantly complicate the formulation.
Data Source
AI summary
An aseptically prepared pharmaceutically acceptable azithromycin premix formulation has a pH value of 5.5 to 7.5, preferably 6.0 to 7.0, more preferably 6.3 to 7.0, even more preferably 6.3 to 6.7, for example about 6.5. Preferred embodiments of the aseptically prepared pharmaceutically acceptable azithromycin premix formulation contain azithromycin, a buffering agent, water and optionally a tonicity adjusting agent and are stable for one month, three months, six months, nine months, twelve months, fifteen months, eighteen months or even twenty-four months, during storage at refrigerated temperatures, such as about 5° C., even without any additional components beyond the azithromycin, the buffering agent, and the optional tonicity adjusting agent in the premix formulation. The pharmaceutically acceptable azithromycin premix formulation may be aseptically filled into a container, preferably a glass or flexible container, to form a sterile pharmaceutical azithromycin premix product which does not undergo terminal sterilization. The azithromycin premix product can be a single use premix which is a sterile, stable and ready-to-use aqueous solution for parenteral administration, for example intravenous (IV) administration such as IV infusion, and requires no dilution prior to parenteral administration.