Dual-HPMCAS Enteric Coating for Granule Water Resistance
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Solution Overview
Problem
Existing enteric coated granules face challenges in achieving controlled dissolution in water with a small amount of coating, while maintaining water resistance and meeting the requirements of various pH-based dissolution tests as per the Japanese Pharmacopoeia.
Innovation Solution
The development of an enteric coated granule with two layers of hydroxypropylmethyl cellulose acetate succinate (HPMCAS) coatings, where the first layer has a higher solubility pH and the second layer has a lower solubility pH, applied using an aqueous dispersion type coating method to achieve controlled dissolution in water with reduced coating amount.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a large amount of enteric coating is applied to achieve water resistance, then water resistance is improved, but coating amount and production time increase
Solution Approach 1:
The enteric coating is divided into multiple layers with different solubility pH characteristics. The first enteric coating layer has a solubility pH of 6.0 or higher, while the second enteric coating layer has a solubility pH of 5.0 or lower. This segmentation allows each layer to perform specific functions: the first layer provides water resistance and protects against water penetration, while the second layer ensures dissolution at appropriate pH levels, thereby achieving water resistance with reduced total coating amount
Solution Approach 2:
Different regions of the coating structure have different properties. The first enteric coating layer (outer layer) is designed with higher solubility pH characteristics for water resistance, while the second enteric coating layer (inner layer) is designed with lower solubility pH characteristics for controlled dissolution. This local differentiation of coating properties optimizes both water resistance and dissolution characteristics without requiring excessive coating material
2Manufacturing precision
If multiple pH-based dissolution tests are conducted to meet Japanese Pharmacopoeia requirements, then dissolution control is improved, but test complexity and time increase
Solution Approach 1:
The coating structure is designed in advance with two distinct enteric coating layers having different solubility pH characteristics during the manufacturing process. This preliminary structuring ensures that the granule will automatically pass multiple pH-based dissolution tests (including pH 1.2, pH 6.8, and water dissolution tests) without requiring additional testing or adjustment, as the layered structure inherently provides the required dissolution control across different pH environments
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 provides water resistance and sufficient coating properties with a smaller coating amount, protecting the granule from water penetration and reducing production time and costs, while maintaining effective dissolution across different pH levels.
Implementation Method 1
an aqueous type enteric coating method comprising a step of spraying an aqueous dispersion of enteric base material powders to form an enteric film
Implementation Method 2
The dispersion thus sprayed adhere uniformly to the surfaces of the coating objects
Implementation Method 3
at least two enteric coating layers different in the solubility pH... a first enteric coating layer having a solubility pH of 6.0 or higher... and a second enteric coating layer having a solubility pH of 5.0 or lower
Implementation Method 4
a plasticizer sprayed simultaneously during coating penetrates into the particles of the enteric base material and plasticizes the enteric base material, leading to the formation of a film
Data Source
AI summary
The present invention is an enteric coated granule having controlled dissolution in water even at a small coating amount; and a preparation method thereof. More specifically, provided are an enteric coated granule comprising a raw granule or a granule comprising a raw granule and at least one layer covering the raw granule, a first enteric layer covering the raw granule or the granule, and a second enteric layer formed over the first enteric layer, wherein the first and the second enteric layers comprise a first and a second hydroxypropylmethyl cellulose acetate succinates (HPMCASs) different in solubility pH, respectively, and the solubility pH value of the second HPMCAS of the second enteric layer is lower than that of the first enteric layer; and a preparation method comprising steps of covering a raw granule or a granule comprising a raw granule and at least one layer covering the raw granule with an enteric coating agent comprising a first HPMCAS to form a first enteric layer; and forming, over the first enteric layer, a second coating layer by using a second enteric coating agent comprising a second HPMCAS having a lower solubility pH value than that of the first HPMCAS.