Cyclosporin A Colon-Targeted Formulation
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Solution Overview
Problem
Current orally administered cyclosporin A compositions result in high systemic absorption and side effects due to poor absorption in the colon, necessitating high doses for effective GI tract treatment, and they have undesirable side effects like hypertension and neurotoxicity.
Innovation Solution
A modified release composition comprising a solid colloid core with a hydrogel forming polymer, cyclosporin A, and an oil phase with surfactants, coated with water-soluble cellulose ethers and modified release polymers to control release, specifically designed for targeted delivery to the colon, reducing systemic exposure and increasing local absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of cyclosporin A are administered orally to ensure adequate concentration reaches the colon, then therapeutic efficacy for GI tract conditions is improved, but systemic toxicity and undesirable side effects increase
Solution Approach 1:
The patent applies local quality by designing a modified release composition with a core coating that provides localized drug release specifically in the colon. The coating is engineered to dissolve at colonic pH, ensuring high local concentrations of cyclosporin A reach the target site while minimizing systemic absorption and associated toxicities.
Solution Approach 2:
The patent uses an intermediary approach by introducing a specific coating material as a mediator between the cyclosporin A and the GI tract environment. This coating acts as a controlled release mechanism that facilitates local drug delivery to the colon while preventing premature release and reducing systemic exposure.
2Ease of operation
If oral cyclosporin A compositions are used to treat GI tract conditions, then ease of administration is improved, but absorption efficiency is poor resulting in high systemic exposure
Solution Approach 1:
The patent applies parameter changes by modifying the physical and chemical parameters of the cyclosporin A formulation. The modified release composition uses a coating with specific dissolution characteristics that change based on pH conditions, enabling controlled release in the colon while maintaining oral administration convenience.
3Ease of manufacture
If conventional oral cyclosporin A formulations are used, then manufacturing simplicity is maintained, but systemic blood exposure is high leading to side effects like hypertension and neurotoxicity
Solution Approach 1:
The patent applies segmentation by dividing the drug delivery system into distinct functional components: a core containing cyclosporin A and a separate coating layer with controlled release properties. This segmented structure enables independent optimization of each component while maintaining overall manufacturing feasibility and reducing systemic exposure.
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 lower systemic blood exposure and higher local concentrations of cyclosporin A in the colon, reducing side effects and enhancing therapeutic efficacy for GI tract conditions while maintaining effective drug levels.
Implementation Method 1
a continuous phase comprising a hydrogel forming polymer
Implementation Method 2
release of the cyclosporin A from the composition
Implementation Method 3
an oil phase comprising an oil and one or more surfactants
Implementation Method 4
the surfactant comprises a surfactant selected from: fatty acid glycerides, polyethylene glycol fatty acid esters
Implementation Method 5
the first coating comprises a water-soluble cellulose ether or a water-soluble derivative of a cellulose ether
Implementation Method 6
a polymer specifically susceptible to degradation by bacterial enzymes in the gastrointestinal tract
Implementation Method 7
a pH dependent polymer
Data Source
Figure 1A~1B
Figure 2~3
Figure 4~5
AI summary
A modified release composition comprising cyclosporin A for oral administration. The composition may comprise a core and a modified release coating, wherein the core comprises a hydrogel- forming polymer matrix and cyclosporin A. The composition may be in the form of a minibead. The compositions provide a pharmacokinetic profile and dissolution profile which provides release of cyclosporin A in the lower GI tract whilst minimising systemic exposure. Also disclosed are uses of the composition in the treatment of conditions affecting the lower GI tract, particularly the colon.