Ciclesonide Suspension Stability via Filtration Sterilization
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Solution Overview
Problem
Existing methods for producing sterile aqueous suspensions for mucous membrane administration, such as nasal and ophthalmic formulations, face challenges in maintaining long-term dispersion stability and safety due to the destruction of dispersants during sterilization processes like autoclave or filtration, leading to reduced drug absorption and irritability.
Innovation Solution
A sterile aqueous suspension of ciclesonide is achieved by using a microgel formed from crosslinked water-soluble polymers like gellan gum or carrageenan, combined with a water-soluble ionic polymer like carmellose sodium, which maintains homogenous dispersion over time and prevents adhesion, using methods like filtration and crosslinking via electrostatic or hydrogen bonds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If autoclave sterilization or radiation sterilization is used to obtain sterile aqueous suspension, then sterility is achieved, but the structure of water soluble polymers (dispersants) is destroyed leading to poor long-term dispersion stability
Solution Approach 1:
The patent applies preliminary action by performing sterilization by filtration on the aqueous suspension containing water soluble polymers and ciclesonide before the polymers are exposed to destructive sterilization methods. This preliminary filtration sterilization preserves the polymer structure while achieving sterility, and the polymers then serve their dispersant function effectively during long-term storage
Solution Approach 2:
The patent uses sterilization by filtration as an intermediary method that achieves sterility without directly exposing the water soluble polymers to autoclave heat or radiation. The filtration process acts as a mediator that separates the sterilization function from the polymer structure, allowing both sterility and polymer integrity to be maintained
2Reliability
If sterilization by filtration is used to obtain sterile aqueous suspension, then sterility is achieved, but the viscosity must be reduced which deteriorates homogeneous dispersion of drug during storage
Solution Approach 1:
The patent applies parameter changes by selecting water soluble polymers with specific molecular weights and concentrations that allow the suspension to pass through 0.22 μm sterile filters while maintaining sufficient viscosity for homogeneous drug dispersion. The polymer concentration and molecular weight parameters are optimized to balance filterability with dispersion stability during long-term storage
3Reliability
If additives like salt at saturation concentration or polyhydric alcohol are added to enable autoclave sterilization, then sterile aqueous suspension is obtained, but drug absorption through mucous membrane decreases and irritability is induced
Solution Approach 1:
The patent extracts and eliminates harmful additive ingredients like salt at saturation concentration and polyhydric alcohol from the formulation. Instead, it uses water soluble polymers that can withstand sterilization by filtration without requiring these harmful additives, thereby achieving sterility while avoiding mucous membrane irritability and maintaining drug absorption
Solution Approach 2:
The patent replaces complex multi-component systems requiring harmful additives with a simpler formulation using water soluble polymers and sterilization by filtration. This simpler approach achieves the same sterility goal without the harmful side effects of salt and polyhydric alcohol additives
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 solution ensures stable, long-term dispersion of ciclesonide with improved absorption and reduced irritability, maintaining viscosity suitable for mucous membrane administration and preventing phase separation during storage and use.
Implementation Method 1
crosslinking via electrostatic or hydrogen bonds
Implementation Method 2
crosslinking via electrostatic or hydrogen bonds
Implementation Method 3
a microgel obtained by microgelation of a water soluble polymer by crosslinking
Implementation Method 4
a water soluble ionic polymer like carmellose sodium
Data Source
AI summary
The present invention relates to a sterile aqueous suspension containing ciclesonide, a microgel and a water soluble ionic polymer. The present invention provides a sterile aqueous suspension in which ciclesonide is dispersed homogeneously over a long period of time.