Fusidic Acid Cream In Situ Formation Under Nitrogen
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Solution Overview
Problem
Current Fusidic acid creams are unstable due to rapid oxidation of fine Fusidic acid particles during manufacture and storage, leading to reduced potency and short shelf life, while existing Sodium Fusidate-based dermaceuticals are limited to ointment form, which is less preferred for topical applications.
Innovation Solution
A process to create a Fusidic acid cream in situ from Sodium Fusidate under an oxygen-free environment using inert gas, resulting in a cream with enhanced stability and finer particle size, incorporating a cream base with preservatives, co-solvents, emulsifiers, and waxy materials, and optionally including buffering agents, antioxidants, chelating agents, and humectants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If fine powder form of Fusidic acid is used as source API, then dermal contact and penetration is enhanced, but chemical stability deteriorates due to rapid oxidation
Solution Approach 1:
The patent applies inert atmosphere by conducting the cream preparation process under nitrogen gas environment. The apparatus includes a nitrogen inlet connected to the reaction vessel, and the entire process of converting Sodium Fusidate to Fusidic acid and incorporating it into the cream base is performed under nitrogen atmosphere. This prevents oxidation of the fine Fusidic acid particles during manufacture, resolving the contradiction between achieving fine particle dispersion (for better dermal contact) and maintaining chemical stability (by preventing oxidation).
2Ease of manufacture
If Fusidic acid is exposed to Oxygen during manufacture and handling, then processing is simplified, but potency reduces due to degradation
Solution Approach 1:
The patent maintains nitrogen atmosphere throughout the entire manufacturing process, from dissolving Sodium Fusidate in the aqueous phase to acidification and cream formulation. This continuous inert environment protection ensures that while processing steps are performed, the Fusidic acid particles do not暴露 to oxygen, thus preventing degradation and maintaining potency throughout manufacture and handling.
Solution Approach 2:
The patent performs the conversion of Sodium Fusidate to Fusidic acid in situ within the cream formulation under nitrogen atmosphere, rather than pre-preparing Fusidic acid powder separately. This preliminary action of converting the salt to the acid form directly in the protected environment eliminates the need for separate handling and storage of fine Fusidic acid powder, thus maintaining potency while simplifying the manufacturing process.
3Stability of the object's composition
If Sodium Fusidate is used as starting material, then stability is improved, but particle size becomes coarse and uneven
Solution Approach 1:
The patent dissolves Sodium Fusidate completely in the aqueous phase under nitrogen atmosphere before acidification. This preliminary dissolution ensures uniform distribution of the salt molecules. When acid is added and Fusidic acid precipitates, it forms fine and uniform particles throughout the cream base, rather than coarse aggregates. This preliminary dissolution step maintains both stability (by using Sodium Fusidate as starting material) and particle size uniformity (by ensuring complete dissolution before conversion).
Solution Approach 2:
The patent controls the pH transition during acidification of the Sodium Fusidate solution. By carefully adjusting the acid addition rate and monitoring pH changes, the patent ensures controlled precipitation of Fusidic acid from the dissolved state, resulting in fine and uniform particle size distribution while maintaining the stability benefits of starting from Sodium Fusidate.
4Ease of manufacture
If Fusidic acid is retrieved from wet cake, then processing is simplified, but stability deteriorates due to drying and oxygen exposure
Solution Approach 1:
The patent performs the conversion of Sodium Fusidate to Fusidic acid and the cream formulation in a single continuous process under nitrogen atmosphere. The Fusidic acid is incorporated into the cream base in situ before any drying or wet cake formation occurs. This preliminary incorporation eliminates the need for separate retrieval and drying steps, thus maintaining both processing simplicity and stability by avoiding oxygen exposure during what would otherwise be necessary handling steps.
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 cream exhibits improved chemical stability, microbial sensitivity, and therapeutic efficacy with reduced particle size, extending shelf life and providing a superior cream formulation over conventional Fusidic acid creams.
Implementation Method 1
a serious shortcoming of the fine size of Fusidic acid particles is that it presents an enormous surface area for contact and reaction with molecular Oxygen during manufacture, handling, and processing of the cream. This has serious implications to its chemical stability and results in rapid reduction in potency of the API (Fusidic acid) in the final cream formulation. Degradation due to oxidation is a major cause of instability of currently available Fusidic acid creams.
Implementation Method 2
The invention discloses a process to make dermaceutical cream containing Fusidic acid which is formed in situ from Sodium Fusidate as the starting raw material, wherein Sodium Fusidate is converted into Fusidic acid under oxygen-free environment created using inert gas, preferably nitrogen.
Implementation Method 3
It can be obtained from Sodium Fusidate by dissolving the latter in an aqueous phase and adding acid to the solution, whereby Fusidic acid precipitates. However, the Fusidic acid precipitate is difficult to process into a cream form first due to its coarse and uneven particle size
Data Source
AI summary
The invention discloses a process to make dermaceutical cream containing Fusidic acid which is formed in situ from Sodium Fusidate as the starting raw material, wherein Sodium Fusidate is converted into Fusidic acid under oxygen-free environment created using inert gas, preferably nitrogen. The cream produced by the process of the present invention has greater shelf-life stability and the finer particle size of the API than the conventional creams containing Fusidic acid. The cream produced by the process of the present invention contains Fusidic acid as the API that has been formed in situ from Sodium Fusidate, in a cream base comprising a preservative, an acid, a co-solvent, an emulsifier and a waxy material along with water, preferably purified water. The cream produced by the process of the present invention further optionally contains an ingredient selected from a group comprising, a buffering agent, an anti oxidant, a chelating agent, and a humectant, or any combination thereof.