Granule Production Using Non-Aqueous Plasticizer for Thermal Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing processes for manufacturing granules with aromatic active ingredients face challenges in maintaining stability and optimal use-by date, as they often undergo heat treatments that can deteriorate the active principles and require intermediate drying or cooling steps, leading to potential vapor pocket formation and reduced glass transition temperatures.
Innovation Solution
A process involving a non-aqueous plasticizer like monopropylene glycol (MPG) is used to create a matrix with a glass transition temperature above ambient temperature, allowing for extrusion and cutting of granules without water addition, minimizing heat exposure and vapor formation, and incorporating an emulsifier for optimal dispersion of the active principle.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If water is added to the mixture to facilitate extrusion, then the matrix becomes more plastic and easier to shape, but the glass transition temperature of the granules decreases, compromising stability
Solution Approach 1:
The patent replaces water with a non-aqueous plasticizer (monopropylene glycol), fundamentally changing the chemical parameter of the liquid additive. This substitution maintains the plasticizing effect needed for extrusion while preventing the depression of glass transition temperature, as non-aqueous plasticizers do not have the same Tg-lowering effect as water in carbohydrate matrices
Solution Approach 2:
The non-aqueous plasticizer acts as an intermediary substance that mediates between the opposing requirements of matrix plasticity and high glass transition temperature. It provides the necessary plasticization for extrusion processing while simultaneously maintaining the thermal stability and glassy state of the final granule product
2Productivity
If the granules are cut directly at the extruder outlet without intermediate drying or cooling, then the process is simplified and productivity increases, but the matrix must be maintained at precise temperature to remain plastic
Solution Approach 1:
The process maintains continuous operation from extrusion through direct cutting without interrupting the thermal state of the matrix. The matrix remains in a plastic state throughout the extrusion and cutting operations, eliminating the need for intermediate cooling or drying steps and enabling continuous production
Solution Approach 2:
The use of non-aqueous plasticizer alters the thermal parameters of the matrix, allowing it to remain plastic at higher temperatures for longer durations. This parameter change enables the matrix to withstand the extrusion and cutting process without premature solidification, facilitating direct cutting operations
3Shape
If heat treatment is applied to the matrix during extrusion, then the matrix becomes plastic and can be shaped, but the active ingredient may deteriorate due to thermal stress
Solution Approach 1:
The non-aqueous plasticizer serves as a thermal mediator that enables plasticization at lower temperatures compared to aqueous systems. By reducing the required extrusion temperature through chemical modification of the matrix properties, it protects heat-sensitive active ingredients from thermal degradation while still achieving the necessary plastic state for shaping
4Temperature
If a smaller quantity of water is used to maintain high glass transition temperature, then the stability improves, but the matrix becomes less plastic and harder to extrude
Solution Approach 1:
The non-aqueous plasticizer acts as a superior intermediary compared to water, providing plasticizing effects without the detrimental Tg-lowering properties. It chemically interacts with the carbohydrate matrix to maintain flexibility and processability while preserving the high glass transition temperature necessary for product stability
Solution Approach 2:
The patent changes the chemical parameter of the plasticizing agent from aqueous to non-aqueous, which fundamentally alters the relationship between plasticity and glass transition temperature. This parameter change decouples the two properties, allowing simultaneous optimization of both matrix processability and product stability
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 process results in granules with a glass transition temperature greater than 40°C, maintaining stability for at least 24 months, optimal dosage in solution, and clear water-dispersibility, while avoiding cloudiness and thermal stress on the active ingredients.
Implementation Method 1
these granules have a glass transition temperature, the temperature at which a glassy state passes into an amorphous, rubbery state
Implementation Method 2
the use of an extrusion pressure such that extrusion, which necessarily takes place at a temperature above the glass transition temperature, can take place while the mass in the molten state is still plastic
Implementation Method 3
transformation of the matrix in an extruder at an extrusion temperature to obtain an amorphous melt matrix
Implementation Method 4
the active ingredient is associated with an emulsifier facilitating the dispersion of the active ingredient in the melt, and the dispersion of the active ingredient in the form of a fine emulsion in the aqueous solution
Data Source
AI summary
The invention concerns a method for producing granules containing at least one active ingredient and stable at ambient temperature, comprising the successive steps of: (1) preparing a matrix free of active ingredient by mixing, without the addition of water, an encapsulation vehicle for the active ingredient and a non-aqueous plasticiser compatible with said vehicle and with the chosen active ingredient, the encapsulation vehicle and the plasticiser being present in amounts that give the matrix a vitreous transition temperature higher than ambient temperature, (2) heating the matrix in an extruder to an extrusion temperature in order to obtain an amorphous melt matrix, (3) injecting the active ingredient into the melt matrix, in order to provide the melt mass with a given active agent, (4) extruding the melt mass provided with the active ingredient through a die and cutting same into granules at an exit point of this mass from the die. The invention is applicable in the food industry, cosmetics and pharmaceutical fields.