Helical Fluidized Bed Spray Drying for Exenatide Stabilization

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing methods for stabilizing biological proteins and cells, such as freeze-drying, spray-drying, and microencapsulation, often result in denaturation and instability due to environmental factors, limiting their shelf life and effectiveness in pharmaceutical and biotechnological applications.

Innovation Solution

A process involving spray-drying using a helical fluidized bed technology with a coating liquid containing exenatide, a saccharide, and a water-miscible solvent, where particles move in a helical path within a processing chamber, allowing for efficient microencapsulation and stabilization of exenatide at temperatures between 30°C to 40°C, minimizing denaturation and extending shelf life.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If freeze-drying is used to prepare proteins, then shelf life is extended, but the native structure of the protein is damaged

Engineering Contradiction:
Improveshelf lifeVSAvoidnative structure
Core Design Contradiction:
Duration of action of stationary objectVSStability of the object's composition

Solution Approach 1:

The invention changes the temperature parameter from traditional freeze-drying (below -20°C) to a controlled temperature range of 30-40°C, which prevents protein denaturation while still achieving stabilization through the coating process

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

A coating liquid containing stabilizing agents (saccharides, amino acids, proteins) is applied as an intermediary layer around the protein particles, protecting the native structure during drying and storage

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If spray-drying using heat is used to prepare proteins, then drying efficiency is improved, but the protein denatures due to high temperature

Engineering Contradiction:
Improvedrying efficiencyVSAvoidprotein structure
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The invention fundamentally changes the temperature parameter from conventional spray-drying (>190°C inlet air) to a low temperature range of 30-40°C, maintaining high drying efficiency through the fluidized bed design while preventing protein denaturation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses a fluidized bed system with upward gas flow to enhance heat and mass transfer efficiency, achieving effective drying at low temperatures through improved convective transport rather than relying on high temperature

Inventive Principle:
Principle #29Pneumatics and hydraulics

3Stability of the object's composition

If additives are used during freeze-drying to protect biological protein, then stability is improved, but the additives solidify at different freezing points causing physical separation

Engineering Contradiction:
Improveprotective stabilityVSAvoidhomogeneous structure
Core Design Contradiction:
Stability of the object's compositionVSShape

Solution Approach 1:

The invention changes the processing temperature from the freezing range to 30-40°C, eliminating the freezing point separation issue while maintaining the protective function of additives through the coating process

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The coating liquid containing stabilizing additives is applied to the protein particles before the drying process, ensuring uniform distribution and protection is established in advance, preventing separation during processing

Inventive Principle:
Principle #10Preliminary action

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 method effectively stabilizes exenatide for extended periods without refrigeration, enabling sustained release delivery forms and maintaining biological activity, suitable for various administration routes, including sublingual and mucosal delivery, with improved product quality and reduced solvent residues.

Implementation Method 1

spray-drying-using-heat This process involves spraying a fine mist of solution downwards from the top of a spray tower against an upward current of hot air. The hot air removes water from the droplets before they reach the bottom of the tower.

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 2

fluidising the particles within a processing chamber of an apparatus in such a manner that the particles move in an upward direction within the chamber in a helical path

Methodology Applied
Scientific EffectFluidisation: Fluidisation

Data Source

PatentEP3381299B1Process for preparing products comprising stabilised actives and compositions comprising same
Publication Date: 2020.08.19 BIOLINGUS IP LLC
  • EP3381299B1 patent drawingFigure 1
  • EP3381299B1 patent drawingFigure 2

AI summary

The present invention broadly relates to a process for preparing products comprising active components, particularly exenatide, wherein the active components are stabilised. The invention further relates to compositions comprising the products, and in particular compositions comprising therapeutic biological materials, particularly exenatide.