Coated Particles for Segregation-Free Dual Active Pharmaceutical Formulations

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Solution Overview

Problem

Pharmaceutical formulations combining two active principles face challenges due to heterogeneity in size, shape, and content, leading to segregation issues and increased particle size, making administration difficult, especially when one active principle is at a higher dose than the other, and requiring additional diluents for dose ratio adjustment.

Innovation Solution

Development of coated particles where the core contains the active principle at the highest dose and the coating contains the active principle at the lowest dose, both made with a high percentage of active ingredients and binding agents, with an optional antistatic agent, to maintain a stable dose ratio and prevent segregation, and an additional functional layer for taste masking and controlled release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If two active principles are mixed in a pharmaceutical formulation, then the formulation can combine multiple therapeutic effects, but segregation occurs due to heterogeneity in size, mass and form

Engineering Contradiction:
Improvecombination of active principlesVSAvoidsegregation risk
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent divides the formulation into separate populations: a first population of particles containing a first active principle and a second population of particles containing a second active principle. This segmentation allows each population to be formulated and controlled independently, preventing segregation while maintaining the ability to combine both active principles in the final dosage form.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each particle population is given specific local characteristics - the first population has specific size, mass and form properties optimized for the first active principle, and the second population has properties optimized for the second active principle. This local quality approach allows each active principle to be delivered effectively without causing segregation.

Inventive Principle:
Principle #3Local quality

2Manufacturing precision

If a diluent is added to adjust dose ratio, then the dose ratio can be maintained close to 1, but the unit size and weight increase

Engineering Contradiction:
Improvedose ratio controlVSAvoidunit size and weight
Core Design Contradiction:
Manufacturing precisionVSWeight of moving object

Solution Approach 1:

The patent extracts the dose ratio control function from the bulk formulation and applies it at the particle level. By controlling the size, mass and form of each particle population independently, the dose ratio is maintained close to 1 without requiring additional diluents that would increase unit size and weight.

Inventive Principle:
Principle #2Taking out (Extraction)

3Object-affected harmful factors

If coating is applied to mask unpleasant taste, then taste masking is achieved, but particle size increases

Engineering Contradiction:
Improvetaste maskingVSAvoidparticle size
Core Design Contradiction:
Object-affected harmful factorsVSLength of moving object

Solution Approach 1:

The patent applies coating dynamically - the coating is applied only to the surface of the particles that require it, and the coating thickness and composition are optimized to provide taste masking with minimal impact on particle size. The coating is applied after the particles are formed, allowing precise control over when and where the coating is applied.

Inventive Principle:
Principle #15Dynamics

Data Source

PatentUS7846460B2Composition comprising a mixture of active principles, and method of preparation
Publication Date: 2010.12.07 ETHYPHARM SA

AI summary

Active principle-based coated particle, in which both the core and the coating contain active principle, includes a core which contains a first active principle while the coating contains a second active principle, which is different in nature.