PVA Amorphous Solid Dispersions Using Three-Fluid Spray Drying

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Solution Overview

Problem

The challenge of formulating amorphous solid dispersions of poorly soluble active pharmaceutical ingredients (APIs) using polyvinyl alcohol (PVA) is hindered by the limited solubility of PVA in organic solvents, making it difficult to achieve a stable, fully amorphous state, which is crucial for enhancing solubility and bioavailability.

Innovation Solution

The use of PVA with a hydrolysis degree of 90% or lower, combined with a three-fluid nozzle spray-drying technique, allows for the preparation of amorphous solid dispersions by dissolving the API and PVA in different solvents, ensuring complete dissolution and stability of the amorphous form.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PVA is used as a carrier polymer for spray-drying to form amorphous solid dispersions, then the API can be stabilized in an amorphous state with improved solubility, but PVA has limited solubility in organic solvents which hinders complete dissolution and amorphization

Engineering Contradiction:

Improvestability of amorphous stateVSAvoiddissolution of PVA in organic solvents

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the chemical parameter of PVA by selecting specific grades with hydrolysis degrees between 70-90% and molecular weights of 10,000-100,000. These parameter modifications optimize the balance between water solubility and organic solvent compatibility, enabling complete dissolution in the organic-aqueous solvent mixture while maintaining the ability to stabilize the amorphous API state during spray-drying.

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If a common solvent system is used to dissolve both API and PVA, then the formulation process is simplified, but the limited solubility of PVA in organic solvents prevents complete dissolution

Engineering Contradiction:

Improveformulation process complexityVSAvoidcomplete dissolution of PVA

Core Design Contradiction:

Device complexityVSManufacturing precision

Solution Approach 1:

The patent employs a composite solvent system combining organic solvent (e.g., ethanol, isopropanol) and aqueous phase in specific ratios. This composite approach leverages the organic solvent's ability to dissolve the lipophilic API and the aqueous phase's ability to dissolve PVA, achieving complete dissolution of both components while maintaining process simplicity.

Inventive Principle:

Principle #40Composite materials

3Reliability

If PVA with high hydrolysis degree is used to improve water solubility, then the polymer is more water soluble, but the solubility in organic solvents remains limited

Engineering Contradiction:

Improvewater solubility of PVAVSAvoidsolubility in organic solvents

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent optimizes the hydrolysis degree parameter of PVA to a specific range (70-90%) rather than using fully hydrolyzed PVA. This parameter adjustment maintains sufficient water solubility for the aqueous phase while retaining enough vinyl acetate groups to provide compatibility with organic solvents, thereby achieving versatility in the mixed solvent system.

Inventive Principle:

Principle #35Parameter changes

4Productivity

If spray-drying is used to rapidly evaporate solvent and form amorphous particles, then the amorphous state is achieved with improved dissolution, but the process requires complete dissolution of API and polymer in the feed solution

Engineering Contradiction:

Improvedrying speed and amorphization efficiencyVSAvoidcomplete dissolution of components

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent uses a composite solvent system with optimized organic-to-aqueous ratio to ensure complete dissolution of both the lipophilic API and the PVA carrier before spray-drying. This complete dissolution in the feed solution is critical for the rapid evaporation process to produce fully amorphous particles without crystallization during the high-speed drying.

Inventive Principle:

Principle #40Composite materials

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

This approach results in improved amorphization, dissolution, and stability of APIs, leading to enhanced solubility and bioavailability, particularly for poorly water-soluble drugs, and prevents crystallization during storage.

Implementation Method 1

Spray Drying (SD) can be described as a solvent evaporation method as the liquid feedstock in which API and polymer are dissolved, is forwarded and sprayed into a drying chamber to produce dried particulates

Methodology Applied

Scientific EffectEvaporation: Evaporation

Implementation Method 2

The liquid is atomized by a stream of gas that can be either air or an inert gas of choice

Methodology Applied

Scientific EffectAtomization: Aerosol

Implementation Method 3

The polymer reduces the molecular mobility of the API, increases the glass transition temperature, protects the API from re-crystallization

Methodology Applied

Scientific EffectGlass transition:

Data Source

PatentUS20260083676A1Spray-dried amorphous solid dispersions and method for preparation

Publication Date: 2026.03.26 MERCK PATENT GMBH

AI summary

The present invention relates to the use of polyvinyl alcohol for spray-drying to form an amorphous solid dispersion of an active pharmaceutical ingredient in a polyvinyl alcohol matrix. Furthermore, the invention relates to a process for producing an amorphous solid dispersion of an active pharmaceutical ingredient in a polyvinyl alcohol matrix by spray-drying.