Enteric-Coated C21 Composition for Delayed Oral 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 form of N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide (C21) that can be effectively administered orally.
Innovation Solution
A pharmaceutical dosage form is developed 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, allowing for oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If C21 is administered orally without enteric coating, then the dosage form is simple and easy to manufacture, but C21 is released in the stomach causing instability and reduced efficacy
Solution Approach 1:
An enteric coating layer is introduced as an intermediary between the C21 core and the stomach environment. This coating acts as a mediator that prevents direct contact between C21 and gastric fluids, thereby protecting the unstable compound while maintaining a relatively simple overall dosage structure.
Solution Approach 2:
A thin enteric coating film is applied to the C21 core or carrier particles. This flexible film provides protection during gastric passage while allowing for simple manufacturing processes such as spray coating or dip coating, balancing stability requirements with manufacturing simplicity.
2Reliability
If C21 is released in the stomach, then the dosage form achieves rapid release, but C21 degrades due to stomach acid reducing therapeutic effect
Solution Approach 1:
The enteric coating is applied in advance to the C21 core or carrier particles before administration. This preliminary protective action ensures that C21 is protected from gastric acid before it encounters the harsh stomach environment, preventing degradation while maintaining timely release in the intestine.
Solution Approach 2:
The release characteristics of C21 are changed by modifying the coating properties rather than changing the core formulation. By adjusting enteric coating parameters such as thickness, composition, and permeability, the release timing is optimized to balance protection during gastric transit with timely release in the intestine for therapeutic efficacy.
3Stability of the object's composition
If carrier materials are used to maintain C21 stability, then C21 homogeneity and stability are improved, but the manufacturing process becomes more complex
Solution Approach 1:
The dosage form is segmented into distinct functional components: C21 core, carrier material, and enteric coating. This segmentation allows each component to be optimized independently for its specific function while using standard manufacturing techniques for assembly, such as granulation followed by coating, which balances complexity with manufacturing feasibility.
Solution Approach 2:
A composite structure is created combining C21 with compatible carrier materials that provide both physical support and chemical stability. The enteric coating is then applied to this composite, creating a multi-layered structure that maintains C21 homogeneity and stability while using well-established composite material processing techniques.
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.