Lipid-Coated Agglomerated API Particles for Taste Masking

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Solution Overview

Problem

Current methods for taste-masking of orally disintegrating and direct-to-mouth drug formulations face challenges with mechanically unstable and heat-sensitive active pharmaceutical ingredients (APIs), particularly in achieving immediate release and stable dissolution profiles, as existing coatings can delay drug release and are unsuitable for temperature-sensitive compounds.

Innovation Solution

A coating composition comprising 70-90% of a solid triglyceride with a melting range above 20°C and 10-30% polysorbate is applied to agglomerated API particles, allowing for immediate release and effective taste-masking, using a fluid-bed coater at moderate temperatures to maintain stability and prevent polymorphic changes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If a conventional polymeric coating is applied to mask taste, then taste-masking is achieved, but the coating process requires heat and mechanical stress that cause disintegration of mechanically unstable API particles

Engineering Contradiction:
ImprovetasteVSAvoidmechanical stability of API particles
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state of the coating material from solid polymeric form to liquid lipid form, allowing coating at lower temperatures and without mechanical stress, thus preserving the mechanical stability of mechanically unstable API particles while achieving effective taste-masking

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces mechanical coating methods (spray coating, pan coating) that apply heat and mechanical stress with a fluid-bed coating method using liquid lipids that penetrate and coat particles without mechanical agitation, preventing disintegration of fragile API agglomerates

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Object-affected harmful factors

If a lipidic coating is applied to mask taste, then taste-masking is achieved, but the coating delays drug release and compromises immediate release requirements

Engineering Contradiction:
ImprovetasteVSAvoiddrug release rate
Core Design Contradiction:
Object-affected harmful factorsVSSpeed

Solution Approach 1:

The patent creates a heterogeneous coating structure where the lipid coating provides taste-masking on the particle surface while allowing localized drug release through controlled diffusion and dissolution pathways, achieving both taste-masking and immediate release requirements

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses composite lipid formulations combining multiple lipids with different melting points and viscosities to create a coating that provides both taste-masking properties and controlled drug release characteristics, achieving immediate release while masking taste

Inventive Principle:
Principle #40Composite materials

3Ease of manufacture

If thermal processing methods are used to apply lipid coating, then coating is achieved, but temperature-sensitive APIs undergo polymorphic changes and degradation

Engineering Contradiction:
Improvecoating applicationVSAvoidpolymorphic stability of API
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent changes the temperature parameter of the coating process by using liquid lipids at lower temperatures rather than hot-melt methods, enabling coating application without causing polymorphic changes or degradation of temperature-sensitive API compounds

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses liquid lipids as an intermediary coating medium that can be applied at lower temperatures without directly heating the API, thus preventing thermal-induced polymorphic changes while still achieving effective coating and taste-masking

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of operation

If high-dose drugs are formulated as orally disintegrating tablets or direct-to-mouth granules, then swallowability is improved, but taste contact with oral mucosa increases and becomes more challenging to mask

Engineering Contradiction:
ImproveswallowabilityVSAvoidtaste contact with oral mucosa
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent applies a thin lipid-based coating film to the surface of high-dose API particles, creating a flexible barrier that masks taste while allowing the particles to maintain their orally disintegrating or direct-to-mouth formulation characteristics for improved swallowability

Inventive Principle:
Principle #30Flexible shells and thin films

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 enables rapid and stable drug release, ensuring at least 75% of the API is dissolved within 45 minutes, while maintaining effective taste-masking and physical stability, even for temperature-sensitive compounds, without the drawbacks of polymorphic changes or equipment clogging.

Implementation Method 1

The coating serves as a physical barrier layer between the active ingredient and the patient's taste buds and olfactory receptors

Methodology Applied
Scientific EffectPhysical barrier:

Implementation Method 2

Lipidic coating systems, such as coatings based on waxes like carnauba wax, do not require a solvent to be applied to drug-containing cores: They may often be used as melts in hot-melt coating processes

Methodology Applied
Scientific EffectHot-melt coating:

Implementation Method 3

Aqueous coating systems also consume substantial energy, as the polymeric coating material must be heated above its film-forming temperature in order to coalesce

Methodology Applied
Scientific EffectFilm-forming temperature:

Implementation Method 4

the capsule shell itself provides a barrier which prevents contact between the active ingredient and the oral mucosa of the patient during administration

Methodology Applied
Scientific EffectPhysical barrier:

Data Source

PatentEP3157506B1Taste-masked oral pharmaceutical composition
Publication Date: 2020.08.26 HERMES ARZNEIMITTEL GMBH

AI summary

The invention provides coated particles with a taste-masked drug substance. The particles comprise a core with the agglomerated active ingredient and a coating comprising a triglyceride and a surfactant. The particles exhibit rapid drug release and a stable release profile. Moreover, the invention provides a hot-melt coating method for manufacturing such particles, and pharmaceutical compositions comprising the particles. The method allows the coating of core particles at moderate temperatures, thereby preventing the degradation of the thermolabile active ingredient.