Paracetamol Suspension Particle Sizing for Browning Control
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Solution Overview
Problem
Existing paracetamol liquid suspensions face challenges with sedimentation and browning over time, particularly due to large particle sizes, which can lead to discoloration and the need for dyes to mask these changes, posing issues for patient acceptance and product stability.
Innovation Solution
Formulating paracetamol liquid suspensions with particles having a d50 of less than or equal to 10µm and a d90 of less than or equal to 35µm, ensuring the suspensions are substantially dye-free and optionally free of invert and reducing sugars, thereby reducing sedimentation and browning over prolonged periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If paracetamol particles with larger average size are used in liquid suspension, then manufacturing cost and ease of formulation are improved, but sedimentation rate increases and browning discoloration occurs during storage
Solution Approach 1:
The patent applies parameter changes by reducing the particle size of paracetamol from conventional larger sizes to a specific range (d50 ≤ 10μm, d90 ≤ 35μm). This parameter modification resolves the contradiction by preventing sedimentation and browning during storage while maintaining ease of formulation through controlled particle size distribution.
Solution Approach 2:
The patent applies segmentation by dividing paracetamol into fine particles with a controlled size distribution (d50 ≤ 10μm, d90 ≤ 35μm). This segmentation prevents the particles from settling and undergoing browning reactions, thereby improving storage stability while maintaining formulation simplicity.
2Device complexity
If paracetamol particles with larger average size are used in liquid suspension, then formulation simplicity is improved, but browning discoloration increases during prolonged storage
Solution Approach 1:
The patent modifies the particle size parameter of paracetamol to d50 ≤ 10μm and d90 ≤ 35μm. This parameter change eliminates browning discoloration during storage while keeping the formulation simple and free from additional masking agents.
Solution Approach 2:
The patent converts the potential harm of fine particle sedimentation into a benefit by carefully controlling the particle size distribution. The fine particles remain suspended without settling, and the formulation becomes dye-free while maintaining simplicity.
3Illumination intensity
If dyes are added to mask discoloration in paracetamol suspension, then appearance is improved, but product complexity and potential patient allergies increase
Solution Approach 1:
The patent extracts and eliminates dyes from the formulation by preventing discoloration at its source through fine particle size control (d50 ≤ 10μm, d90 ≤ 35μm). This removal of dyes simplifies the product and eliminates allergy concerns while maintaining acceptable appearance.
Solution Approach 2:
The patent converts the potential harm of discoloration into a benefit by using fine particle size to prevent the discoloration mechanism itself, making dye addition unnecessary and simplifying the overall product formulation.
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 formulation achieves a storage-stable, organoleptically pleasing suspension with reduced sedimentation and browning, maintaining a commercially acceptable appearance without the need for dyes, even after 12-36 months.
Implementation Method 1
One challenge associated with liquid suspensions is sedimentation, that is the tendency for particles in suspension to settle out of the fluid. Among all the ingredients of a suspension, the suspended phase (i.e., containing API particles, in this case, paracetamol particles) is one of the most critical components since it might tend to sediment over time and under specific conditions.
Implementation Method 2
Stokes' law is often used to express the sedimentation rate: Where dS/dt is the sedimentation rate, d is the diameter of the particles, ρP is the density of the particles, ρM is the density of the medium, g is the gravitational constant and η is the viscosity of the medium. According to Stokes' law, the sedimentation rate of a suspension decreases with decreasing the particle diameter
Data Source
Figure 1(a)~1(e)
Figure 2
Figure 3
AI summary
The present invention relates to pharmaceutical liquid suspensions suitable for oral administration. More specifically, the present invention relates to pharmaceutical liquid suspensions containing paracetamol wherein the suspensions are formulated with paracetamol particles having a d50 of less than or equal to 10µm and a d90 of less than or equal to 35µm such that browning discoloration is reduced during prolonged storage.