Spironolactone Aqueous Formulation Stability and Resuspendability
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Solution Overview
Problem
Current spironolactone formulations lack long-term stability and uniformity, leading to potential microbial contamination, dosing errors, and reduced patient compliance due to sedimentation issues, as they require vigorous shaking for uniform dispersion.
Innovation Solution
A pharmaceutical composition comprising spironolactone, xanthan gum, an anti-foaming agent, preservative, dispersing agent, sweetening agent, flavoring agent, and a buffer, formulated to maintain pH between 4.5 and 5.5, which ensures stability and easy resuspendability, reducing sedimentation and dosing errors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If compounded spironolactone formulations are prepared from tablets or powder, then the drug can be administered in liquid form, but the formulations suffer from microbial contamination risk and poor long-term stability
Solution Approach 1:
The patent optimizes the pH parameter of the aqueous formulation to maintain spironolactone stability. By controlling the pH within a specific range, the formulation achieves long-term stability while remaining in liquid form, resolving the contradiction between adaptability and reliability.
Solution Approach 2:
The patent introduces a preservative system as an intermediary component to prevent microbial contamination. This mediator substance protects the liquid formulation from degradation while maintaining the desired liquid administration form, thus improving reliability without sacrificing adaptability.
2Ease of manufacture
If simple syrup vehicle with alcohol and sodium benzoate is used as preservative, then the formulation can be prepared extemporaneously, but the stability is limited and only acceptable for short-term use
Solution Approach 1:
The patent modifies the preservative system parameters by optimizing the concentration and type of preservatives used. This allows the formulation to maintain ease of manufacture while achieving extended shelf life, resolving the contradiction between ease of manufacture and duration of action.
3Stability of the object's composition
If spironolactone is suspended in aqueous formulation, then the drug becomes more stable, but sedimentation occurs requiring vigorous shaking for uniform dispersion
Solution Approach 1:
The patent introduces suspending agents and surfactants as intermediary substances to prevent sedimentation. These mediators maintain uniform dispersion of spironolactone in the aqueous formulation, improving ease of operation while preserving stability.
Solution Approach 2:
The patent optimizes physical parameters such as particle size reduction and viscosity control to improve resuspendability. By changing these parameters, the formulation maintains stability while requiring minimal shaking, resolving the contradiction between stability and ease of operation.
4Adaptability or versatility
If compounded formulations are prepared in pharmacy, then tablet administration can be avoided for patients, but dosing errors and stability issues arise
Solution Approach 1:
The patent provides specific formulation recipes with precise ingredient concentrations and preparation instructions. This segmentation of the compounding process into controlled steps ensures dosing accuracy while maintaining the adaptability of liquid dosage forms for patients who cannot take tablets.
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 long-term stability and rapid resuspendability within 5-10 seconds, maintaining 100% spironolactone content for extended periods, enhancing patient compliance and reducing the risk of dosing errors.
Implementation Method 1
xanthan gum, in the amount of from 0.18% w/v to 0.36% w/v
Implementation Method 2
an anti-foaming agent; (d) a preservative; (f) a dispersing agent; (g) a sweetening agent; (h) a flavoring agent; (i) optionally a buffer to maintain the pH of the pharmaceutical composition within a range described herein
Implementation Method 3
a dispersing agent
Implementation Method 4
a preservative
Data Source
AI summary
Disclosed herein is a pharmaceutical composition, comprising: (a) spironolactone; (b) a xanthan gum; (c) an anti-foaming agent; (d) a preservative; (f) a dispersing agent; (g) a sweetening agent; (h) a flavoring agent; (i) optionally a buffer to maintain the pH of the pharmaceutical composition within a range described herein; and (j) a sufficient amount of a water vehicle.