Needle-Shaped Active Ingredient Extrudates

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Solution Overview

Problem

The extrusion process for mixtures containing needle-shaped active ingredients is hindered by blockages in the nozzle plate and poor flowability, leading to inconsistent dosing rates and manufacturing challenges, even when the particle size is significantly smaller than the strand diameter.

Innovation Solution

The development of extrudates with a needle-shaped pharmaceutically active substance having a particle size ratio of at least 1:20 to the strand diameter, using a lipid base as an auxiliary, and extruding below the melting range of the lipid base, which improves process uniformity and reproducibility by ensuring the active ingredient is finely ground to facilitate smooth extrusion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If needle-shaped active ingredients are used in extrusion process, then high drug loading (up to 80%) is achieved, but nozzle plate blockages and poor flowability occur

Engineering Contradiction:
Improvedrug loadingVSAvoidextrusion processability
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The needle-shaped active ingredients are ground to a specific particle size range (d90 ≤ 10 μm, preferably d90 ≤ 5 μm) before extrusion. This preliminary size reduction prevents nozzle blockages and improves flowability during the extrusion process, enabling high drug loading formulations to be manufactured successfully.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If particle size of needle-shaped active ingredient is reduced to improve flowability, then extrusion process uniformity improves, but manufacturing complexity increases

Engineering Contradiction:
Improveprocess uniformityVSAvoidgrinding equipment requirements
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention specifies precise particle size parameters (d90 ≤ 10 μm, preferably d90 ≤ 5 μm) for the needle-shaped active ingredient. By controlling this critical parameter through grinding, the invention achieves uniform extrusion pressure and consistent dosing rates, while the relatively simple size specification makes the requirement manageable in practice.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If extrusion is performed below melting range of lipid base, then taste masking is maintained, but process temperature control becomes more difficult

Engineering Contradiction:
Improvetaste maskingVSAvoidprocess temperature control
Core Design Contradiction:
Object-affected harmful factorsVSTemperature

Solution Approach 1:

The invention requires monitoring and controlling the extrusion temperature to remain below the melting range of the lipid base throughout the process. This feedback control ensures that the lipid base remains solid, maintaining taste masking properties, while preventing temperature excursions that would compromise the solid structure and cause leakage or loss of taste masking.

Inventive Principle:
Principle #23Feedback

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 allows for the production of extrudates with high drug loading (up to 80%) and consistent pressure, preventing nozzle clogging and ensuring uniform extrusion, even at high process speeds, by reducing the particle size of needle-shaped active ingredients to improve flowability and prevent electrostatic charges.

Implementation Method 1

the extrudate being below the melting range of the substance contained therein

Methodology Applied
Scientific EffectMelting: Melting

Data Source

PatentEP2373287B1Extrudate of needle-like pharmaceutical actives
Publication Date: 2018.05.30 BAYER INTPROP GMBH
  • EP2373287B1 patent drawingFigure 1~2
  • EP2373287B1 patent drawingFigure 3~4
  • EP2373287B1 patent drawingFigure 5~6

AI summary

The invention relates to extrudates comprising at least one pharmaceutically active substance in the shape of pins, wherein the ratio of particle sizes of the spicular pharmaceutically active substance to the strand diameter is at least 1:15, and to the use of said extrudates for producing medications.