Budesonide Modified-Release Composition for Ileal Delivery
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Solution Overview
Problem
Current treatments for IgA nephropathy, a progressive autoimmune kidney disease, are inadequate and often associated with significant side effects, and there is a need for a targeted, local treatment that can reduce the formation of pathogenic IgA antibodies without systemic exposure to immunosuppressive agents.
Innovation Solution
A budesonide formulation with a specific in vitro release profile is administered to the gastrointestinal tract, particularly the distal ileum, to reduce serum levels of BAFF and pathogenic IgA antibodies, while minimizing systemic side effects through targeted local delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic immunosuppressive agents are used to treat IgA nephropathy, then the formation of pathogenic IgA antibodies is reduced, but significant systemic side effects occur
Solution Approach 1:
The treatment is segmented into local (ileal) and systemic components. Budesonide is delivered locally to the ileum where Peyer's patches are concentrated, segmenting the therapeutic action from systemic circulation. This allows the drug to act where needed (reducing pathogenic IgA production at the source) while minimizing systemic exposure and associated side effects.
Solution Approach 2:
The invention applies local quality by concentrating the immunosuppressive action specifically in the ileum rather than distributing it systemically. The enteric-coated budesonide formulation ensures drug release occurs locally at the target site (distal ileum), creating high local concentration where Peyer's patches produce secretory IgA, while maintaining low systemic concentrations to reduce harmful side effects.
2Ease of operation
If conventional dissolution profiles are used for budesonide, then the drug is released throughout the gastrointestinal tract, but targeted delivery to the distal ileum is not achieved
Solution Approach 1:
The invention changes the dissolution parameters of budesonide by using enteric coating materials that are resistant to acid dissolution but dissolve at higher pH values characteristic of the distal ileum. This parameter change (pH-dependent dissolution) enables targeted delivery to the specific anatomical location where therapeutic action is needed, transforming the drug's release behavior from non-selective to location-specific.
Solution Approach 2:
The enteric coating acts as an intermediary between the budesonide drug and the gastrointestinal environment. This coating layer protects the drug from premature release in the stomach and proximal intestine, and mediates controlled release at the target site (distal ileum) where the coating dissolves, enabling precise spatial control of drug delivery.
Data Source
AI summary
The present invention provides for a method of treatment of IgA nephropathy, which method comprises:(i) identifying a pharmaceutically acceptable composition intended to treat IgA nephropathy comprising budesonide and one or more pharmaceutically-acceptable excipients that provide for a modified release of said budesonide after administration to the gastrointestinal tract, which composition fulfils the following requirements in a standard in vitro USP<711>/Ph.Eur. 2.9.3 dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) of said test;(a) the composition fulfils the requirement that no more than about 10% of the budesonide is released into the dissolution medium within about 120 minutes, when the dissolution medium is aqueous and has a pH of about 1.2;(b) the composition fulfils the requirement that no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes; and(c) the composition fulfils the requirement that at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes;(ii) wherein the method comprises the step of administering said composition to a patient with IgA nephropathy in need of said treatment.