Azithromycin Premix Formulation Without Terminal Sterilization

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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, ensuring stability for up to 24 months at refrigerated temperatures and ready for direct parenteral administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If terminal sterilization is used to ensure sterility, then sterility is improved, but drug stability deteriorates due to degradation at high temperatures

Engineering Contradiction:

ImprovesterilityVSAvoiddrug stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The formulation is prepared aseptically before filling into containers, 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 high-temperature sterilization treatment.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The pH of the formulation is optimized to range from 5.5 to 7.5, which prevents drug degradation and maintains stability during storage. This pH parameter change eliminates the need for terminal sterilization while ensuring both sterility and stability.

Inventive Principle:

Principle #35Parameter changes

2Stability of the object's composition

If lyophilized powder is used to maintain stability, then stability is improved, but ease of operation deteriorates due to required reconstitution and dilution steps

Engineering Contradiction:

ImprovestabilityVSAvoidease of administration

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

The formulation combines stability features with ready-to-use convenience by creating a sterile, pH-adjusted aqueous solution that maintains stability without requiring reconstitution or dilution. The buffering agent and pH adjustment are integrated into the final product, merging the benefits of both stable storage and easy administration.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

All preparation steps including pH adjustment, buffering agent addition, and sterile filtration are performed in advance during manufacturing. The product is supplied as a ready-to-use sterile solution, eliminating the need for reconstitution and dilution at the point of administration.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If multiple preparation steps are used to ensure sterility and stability, then reliability is improved, but productivity deteriorates due to time-consuming reconstitution and dilution

Engineering Contradiction:

Improvesterility and stabilityVSAvoidadministration efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

All critical preparation steps including pH adjustment to 5.5-7.5, addition of buffering agents, sterile filtration, and aseptic filling are completed during manufacturing. The product is supplied as a ready-to-use sterile solution that requires no further preparation, significantly improving administration efficiency while maintaining reliability.

Inventive Principle:

Principle #10Preliminary action

4Ease of manufacture

If pH is not controlled to maintain stability, then ease of manufacture is improved, but drug stability deteriorates over shelf-life

Engineering Contradiction:

Improvemanufacturing simplicityVSAvoidshelf-life stability

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The pH is optimized and controlled within the range of 5.5 to 7.5, with buffering agents added to maintain this pH throughout shelf-life. This parameter control ensures drug stability without significantly complicating the manufacturing process, as the pH adjustment is integrated into the formulation preparation steps.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12521411B2Azithromycin premix formulation and product, methods of preparing same, and methods of using same

Publication Date: 2026.01.13 BAXTER INT INC

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.