Vitamin E Particulate Formulation Dust-Free Spray Drying

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Solution Overview

Problem

Existing pharmaceutical formulations using water-soluble vitamin E derivatives and hydrophilic polymers face issues with storage stability, dust formation, tackiness, and phase separation, leading to manufacturing challenges and safety concerns due to the use of organic solvents.

Innovation Solution

A storage-stable, dust-free homogeneous particulate formulation comprising a water-soluble Vitamin E derivative, a hydrophilic polymer, and optional surface-active substances, with a fines fraction less than 10% by weight of particles below 100 μm, produced through a spray drying agglomeration process that ensures the components are miscible and free-flowing, avoiding organic solvents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If water-soluble vitamin E derivatives and hydrophilic polymers are used to enhance solubility and bioavailability, then the solubility and bioavailability of hydrophobic active ingredients are improved, but the formulation exhibits tackiness, forms dust, and suffers from poor storage stability

Engineering Contradiction:
Improvestorage stabilityVSAvoiddust formation and tackiness
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the physical and chemical parameters of the formulation by controlling particle size (Dv10: 10-50 μm, Dv50: 50-100 μm, Dv90: 100-200 μm) and adjusting the composition ratios of vitamin E derivative (5-20%) and hydrophilic polymer (80-95%), thereby eliminating dust formation and tackiness while maintaining storage stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite particulate formulation combining water-soluble vitamin E derivative and hydrophilic polymer in specific ratios with controlled particle size distribution, achieving a material that is both soluble and free from dust and tackiness issues

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If the formulation is made free-flowing and homogeneous to improve processability, then manufacturing reliability is improved, but phase separation may occur during manufacture or storage

Engineering Contradiction:
ImproveprocessabilityVSAvoidphase separation
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent adjusts composition parameters (vitamin E derivative 5-20%, hydrophilic polymer 80-95%) and physical parameters (particle size distribution, moisture content 1-5%) to achieve a formulation that remains homogeneous and free-flowing during manufacturing while preventing phase separation during storage

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent ensures uniform distribution of vitamin E derivative throughout the hydrophilic polymer matrix at the local level, creating a homogeneous structure that prevents phase separation while maintaining good flow properties for manufacturing

Inventive Principle:
Principle #3Local quality

3Ease of manufacture

If organic solvents are used in the manufacture process, then the solubilizing composition can be produced, but safety risks and residual solvent content problems arise

Engineering Contradiction:
ImprovemanufacturabilityVSAvoidsafety risks from organic solvents
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent replaces organic solvent-based manufacturing processes with aqueous spray drying technology, substituting the chemical mechanism of organic solvation with a physical aerosolization and drying process that eliminates organic solvent safety risks while maintaining product manufacturability

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

Solution Approach 2:

The patent uses water as an intermediary medium in the spray drying process instead of organic solvents, allowing for safe and efficient manufacturing of the solubilizing composition without the harmful effects of organic solvent residue

Inventive Principle:
Principle #24Intermediary (Mediator)

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 provides improved processability, stability, and safety by eliminating dust, tackiness, and phase separation, ensuring reliable manufacturing and storage, while maintaining high bioavailability and solubility of the active ingredients.

Implementation Method 1

The process comprises (i) forming an aqueous solution of components (a), (b), and optionally (c) and (d), (ii) atomizing said solution with the help of one or more spray nozzles

Methodology Applied
Scientific EffectAtomization:

Implementation Method 2

It is known that surfactants can be used for enhancing the solubility of hydrophobic active ingredients in an aqueous medium and thus improve bioavailability of the active ingredient

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Implementation Method 3

the components are miscible and free-flowing, avoiding organic solvents

Methodology Applied
Scientific EffectMiscibility:

Data Source

PatentUS9789063B2Storage-stable dust-free homogeneous particulate formulation
Publication Date: 2017.10.17 BASF SE

AI summary

Described is a storage-stable dust-free homogeneous particulate formulation. The formulation consists of (a) at least one water-soluble Vitamin E-derivative, (b) at least one hydrophilic polymer, (c) optionally additional surface-active substances, and (d) optionally additional pharmaceutical additives. The sum of (a), (b), (c) and (d) equals 100% by weight of the formulation. The fines fraction with particle diameters of less than 100 μm is less than 10% by weight. Describe also is a process for manufacturing the formulation, and use of the formulation as a solubilizing composition in pharmaceutical formulations.