pH-Sensitive Enteric Coating for Targeted Enterokine Release
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Solution Overview
Problem
Current pharmaceutical oral dosage forms are ineffective in providing improved preventive and therapeutic measures against metabolic and cardiovascular disorders, as they fail to efficiently stimulate enteroendocrine cells in the jejunum and ileum to release enterokines, such as GLP-1 and PYY, which are crucial for regulating blood sugar levels and improving metabolic functions.
Innovation Solution
A pharmaceutical oral dosage form comprising a core with a pH-sensitive enteric coating that bursts to release active compounds like glucose and other nutrients in the jejunum, specifically targeting enteroendocrine cells to trigger the release of enterokines, utilizing a combination of carbohydrates, fatty acids, and ethanolamides, and incorporating disintegrants for rapid release, ensuring more than 70% of the core is released within two minutes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional oral dosage forms are used to deliver nutritional substances to the ileum, then satiety and metabolic effects are achieved, but the stimulation of enteroendocrine cells in the jejunum and ileum is insufficient to maximize enterokine release
Solution Approach 1:
The dosage form is segmented into distinct functional components: an enteric coating layer that protects and controls release location, a core containing the nutritional substance, and disintegrant agents that enable rapid release at the target site. This segmentation allows the formulation to reliably stimulate enteroendocrine cells in the jejunum and ileum by ensuring the nutritional substance is released at the correct location, thereby maximizing enterokine release efficacy without requiring overly complex manufacturing processes
Solution Approach 2:
The enteric coating acts as an intermediary that mediates between the nutritional substance and the gastrointestinal environment. It protects the nutritional substance from premature release in the stomach and upper intestine, then facilitates controlled release at the target site (jejunum and ileum) where enteroendocrine cells are present. This intermediary function ensures reliable stimulation of enterokine release while maintaining a relatively simple dosage form structure
2Manufacturing precision
If the enteric coating is designed to dissolve in the jejunum, then targeted release and enterokine stimulation are improved, but the coating must withstand varying pH conditions until reaching the target site
Solution Approach 1:
The enteric coating is designed to respond to parameter changes in the gastrointestinal environment, specifically pH changes. The coating remains stable at the lower pH of the stomach and upper intestine, then dissolves when it encounters the higher pH conditions in the jejunum and ileum. This parameter-based control mechanism achieves precise release location targeting while maintaining coating stability during transit, as the coating's dissolution is triggered by the natural pH gradient along the gastrointestinal tract
Solution Approach 2:
The enteric coating utilizes phase transition principles, transitioning from a stable, intact state in the acidic environment to a dissolved state in the higher pH environment of the jejunum and ileum. This phase transition approach allows the coating to maintain its structural integrity and protective function during gastric transit, then rapidly dissolve at the target site to release the nutritional substance and stimulate enteroendocrine cells, achieving both stability and precision requirements
3Productivity
If disintegrants are incorporated for burst release, then enterokine production increases with lower doses, but the disintegration mechanism must be precisely controlled to ensure release within two minutes
Solution Approach 1:
The disintegrant mechanism is designed to trigger periodic action at a specific moment in the gastrointestinal tract. The enteric coating remains intact during transit, then undergoes rapid disintegration when it encounters the appropriate pH conditions in the jejunum and ileum. This timed, periodic disintegration event ensures that the nutritional substance is released in a burst manner within two minutes of reaching the target site, maximizing enterokine production rate while maintaining precise control over the disintegration timing through the pH-sensitive enteric coating design
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 formulation achieves a significant increase in enterokine production, particularly GLP-1 and PYY, with lower doses of active ingredients, enhancing insulin secretion, glucose regulation, and improving metabolic and gastrointestinal functions, compared to previous technologies.
Implementation Method 1
the coating comprises a pH sensitive polymer being selected such that the coating substantially dissolves and/or is substantially degraded in the jejunum of a subject
Implementation Method 2
at least one disintegrant providing a burst release of the ingredients of the core when the coating is substantially degraded and/or dissolved
Data Source
AI summary
The present invention relates to pharmaceutical oral dosage forms releasing compounds in specific parts of the small intestine of a subject, wherein said compounds stimulate enteroendocrine cells in the subject's jejunum and lower small intestine to release one or more enterokines. The present invention also relates to a method of producing such pharmaceutical oral dosage forms. The pharmaceutical oral dosage forms of the invention are particularly for use in the treatment and prevention of metabolic conditions or diseases, osteoporosis, malabsorption conditions, neurodegenerative diseases, conditions of impaired gastro-intestinal function and cardiovascular diseases.