Mesalamine Composition with pH-Varied Enteric Coatings
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Solution Overview
Problem
Mesalamine pharmaceutical compositions face delivery variability due to failure to disintegrate in the gastrointestinal tract, primarily because the target pH is not consistently reached, leading to incomplete release of the active ingredient.
Innovation Solution
A mesalamine pharmaceutical composition comprising multiple dosage elements with different enteric coatings, each soluble at specific pH ranges in an aqueous phosphate buffer, ensuring at least 70-85% of mesalamine release within 60 minutes, thereby minimizing delivery variability by adjusting the pH sensitivity of the coatings.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If a single enteric coating is used on mesalamine tablets, then the formulation is simple, but delivery variability occurs due to failure to disintegrate when target pH is not consistently reached
Solution Approach 1:
The patent divides the single enteric coating into multiple coatings with different pH solubility characteristics. Each coating layer is designed to dissolve at different pH ranges, ensuring that at least one coating will dissolve in the colon regardless of the specific pH conditions encountered in the gastrointestinal tract. This segmentation approach eliminates delivery variability while maintaining formulation simplicity.
Solution Approach 2:
The patent utilizes different pH solubility parameters for the enteric coatings. By selecting coatings with different pH dissolution characteristics (e.g., one coating soluble at pH ≥ 6.0 and another at pH ≥ 7.0), the formulation ensures reliable disintegration across varying gastrointestinal pH conditions, directly addressing the delivery consistency problem.
2Manufacturing precision
If the enteric coating is designed to dissolve at a specific pH, then mesalamine release is controlled, but delivery variability increases when the target pH is not reached in some subjects
Solution Approach 1:
The patent segments the pH-dependent release control into multiple coating layers, each responsive to different pH ranges. This ensures that even if the gastrointestinal tract pH does not reach the target value for a single coating, at least one coating layer will dissolve, maintaining reliable mesalamine release while preserving controlled release characteristics.
Solution Approach 2:
The patent incorporates multiple pH-responsive coatings as a preventive measure against pH variability in the gastrointestinal tract. By having multiple coatings with different pH dissolution thresholds, the formulation is cushioned against the risk of complete disintegration failure, ensuring reliable drug delivery under varying physiological conditions.
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 composition achieves reduced delivery variability by ensuring consistent release of mesalamine across different pH conditions in the gastrointestinal tract, enhancing the effectiveness of mesalamine delivery to the colon for treating colonic disorders.
Implementation Method 1
the first enteric coating is soluble at a pH of 6.4 to 6.8 in an aqueous phosphate buffer and the second enteric coating is soluble in an aqueous phosphate buffer at a pH of 0.2 to 1 units higher than the first enteric coating
Data Source
AI summary
A mesalamine pharmaceutical composition with reduced delivery variability for delivery of mesalamine to the colon that includes multiple dosage elements, and each dosage element includes mesalamine and an enteric coating. The enteric coating of each different dosage element differs so the release point of the mesalamine in the GI tract is varied. In one embodiment, a first dosage element releases about 30% to about 60% by weight of the total mesalamine in the composition after 60 minutes at a pH of about 6.6 in an aqueous phosphate buffer using a paddle apparatus 2 with a paddle speed of 100 rpm and a second dosage element releases about 40% to about 70% by weight of the total mesalamine after 60 minutes at a pH of about 7.2 in an aqueous phosphate buffer using a paddle apparatus 2 with a paddle speed of 100 rpm.