Pellets Formulation via High-Shear Granulation
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Solution Overview
Problem
Current pharmaceutical pellet production methods, such as layering and extrusion-spheronization, face challenges in achieving consistently smooth, non-porous, and high-strength pellets with controlled release profiles, especially for pH-dependent active ingredients with low water solubility, which affects bioavailability and dosage consistency.
Innovation Solution
A high-shear granulation process is employed to produce solid, spherical pellets with a controlled mean Feret diameter and crushing strength, using a mixing phase, granulation phase with calcium chloride solution, spheronization, and drying, resulting in pellets with improved mechanical stability and pH-independent release profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If the layering method is used to produce pellets, then spherical shape and smooth surface are achieved, but surface smoothness is unsatisfactory and pellets bind to each other causing high waste proportion
Solution Approach 1:
The invention changes the process parameters by using high-shear granulation instead of layering, controlling moisture content, and optimizing granulation time to produce pellets with smooth surfaces that do not bind together, thereby reducing waste while maintaining spherical shape
Solution Approach 2:
The invention replaces the mechanical layering process with a high-shear granulation system that uses controlled mechanical energy input to form pellets with desirable surface properties, avoiding the surface roughness and binding issues associated with layering
2Productivity
If extrusion-spheronization process is used, then production efficiency is improved, but pellets exhibit irregular shapes and surfaces resulting in irregular active ingredient release
Solution Approach 1:
The invention optimizes process parameters including shear rate, granulation time, and moisture content to produce pellets with regular shapes and smooth surfaces while maintaining high production efficiency through the high-shear granulation process
Solution Approach 2:
The invention uses dynamic high-shear mixing that creates controlled turbulence and particle interaction, allowing pellets to achieve regular shapes and smooth surfaces during the granulation process while maintaining efficient production
3Ease of manufacture
If pellets have irregular shapes, then production is easier, but release of active ingredient becomes irregular affecting bioavailability
Solution Approach 1:
The invention changes the shape parameter by using high-shear granulation to produce regular-shaped pellets with controlled size distribution, ensuring consistent active ingredient release while maintaining ease of manufacture through the efficient granulation process
4Ease of operation
If pellets have broad particle size distribution, then filling is easier, but coating uniformity deteriorates
Solution Approach 1:
The invention optimizes the particle size distribution parameters to achieve a narrow, controlled size range that allows for uniform coating application while maintaining good filling characteristics through the high-shear granulation process
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 yields pellets with enhanced mechanical stability, homogenous coating, and improved bioavailability of pH-dependent active ingredients by optimizing particle size, shape, and release kinetics, reducing waste and increasing the loading capacity of active ingredients.
Implementation Method 1
a granulation phase commenced with the addition to the powder mixture of a calcium chloride solution as granulation liquid, in which the granulation mass is obtained
Implementation Method 2
the appropriately homogenized powder mixture is mixed with a liquid and kneaded until a homogeneous wet mass is obtained
Implementation Method 3
Said mass is extruded and the extrudate resulting from the extrusion process is spheronized (brought into a spheroid shape)
Implementation Method 4
the extrudate resulting from the extrusion process is spheronized (brought into a spheroid shape)
Implementation Method 5
Finally the raw pellets obtained from the spheronization phase are dried
Data Source
AI summary
A process for preparing pellets by high shear granulation containing a pharmaceutical active ingredient with a pH dependent water solubility, the pellets obtained with said process and pharmaceutical oral dosage forms comprising said pellets.