Enteric C21 Oral Composition for Stomach-Safe Intestinal Release
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Solution Overview
Problem
Current treatments for interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), are limited in efficacy and safety, with existing drugs causing significant side effects and failing to halt disease progression, and there is a need for a stable pharmaceutical formulation of the AT2 receptor agonist C21 that can be administered orally without degradation.
Innovation Solution
A pharmaceutical dosage form is developed for peroral administration that includes C21 or its pharmaceutically-acceptable salt, coated with an enteric substance to prevent release in the stomach and ensure delivery to the small intestine, using specific carrier materials and excipients to maintain stability and homogeneity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If C21 is administered orally without coating, then the dosage form is simple and easy to manufacture, but C21 degrades in the stomach and loses therapeutic efficacy
Solution Approach 1:
The dosage form is segmented into multiple functional layers: an enteric coating layer that protects C21 from stomach acid, and a core layer containing the active ingredient. This segmentation allows the drug to survive gastric conditions and release at the appropriate location in the intestine, resolving the contradiction between simplicity and reliability.
Solution Approach 2:
An enteric coating acts as an intermediary barrier between the stomach environment and the C21 active ingredient. This coating layer mediates the interaction by preventing direct contact between the drug and gastric acid, thereby protecting therapeutic efficacy while maintaining a relatively simple dosage form structure.
2Stability of the object's composition
If C21 is coated with enteric substance, then stomach exposure is minimized and chemical integrity is maintained, but manufacturing process becomes more complex
Solution Approach 1:
The enteric coating is applied as a preliminary protective action during manufacturing, before the product reaches the patient. This preliminary coating ensures chemical integrity is maintained from the outset, and while it adds a manufacturing step, it uses well-established coating technologies that are relatively straightforward to implement.
Solution Approach 2:
The coating process utilizes parameter changes (such as pH-sensitive materials that remain intact in acidic stomach environment but dissolve in intestinal environment) to achieve stable composition. This approach maintains chemical integrity through controlled physical-chemical parameter changes rather than complex manufacturing procedures.
3Speed
If C21 is released in the stomach, then absorption might be faster, but the drug degrades and causes side effects
Solution Approach 1:
The enteric coating converts the harmful acidic stomach environment into a beneficial release mechanism. The coating is specifically designed to resist stomach acid but dissolve in the slightly alkaline intestinal environment, thereby converting the harmful gastric conditions into a controlled release system that protects the drug and enables absorption at the appropriate location.
Solution Approach 2:
The enteric coating serves as an intermediary that prevents direct interaction between C21 and the harmful stomach environment. This mediator layer allows the drug to avoid degradation while maintaining the potential for rapid absorption once released in the intestine, where the coating naturally dissolves.
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 formulation ensures stable delivery of C21 to the gastrointestinal tract, minimizing stomach exposure and maintaining chemical integrity, thereby enhancing treatment efficacy and safety for ILDs like IPF.
Implementation Method 1
coated with an enteric substance to prevent release in the stomach and ensure delivery to the small intestine
Data Source
AI summary
According to the invention there is provided a pharmaceutical composition comprising N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide (C21), or a pharmaceutically-acceptable salt thereof, in which composition the C21 or salt thereof is protected by the presence of a coating comprising an enteric substance. Preferred dosage forms comprise capsules in which C21 or salt thereof is presented in the form of a dry powder mixture or a suspension of particles of C21 in a solvent in which it is insoluble. Such dosage forms find utility in the treatment of lung diseases, such as idiopathic pulmonary fibrosis, sarcoidosis and respiratory virus-induced tissue damage.