Budesonide Orodispersible Effervescent Tablet for Eosinophilic Esophagitis
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Solution Overview
Problem
Current treatments for eosinophilic esophagitis, such as nebulized and swallowed corticosteroids, have limited efficacy and are associated with side effects due to inadequate esophageal targeting and short-term remission maintenance, while long-term use of systemic corticosteroids poses severe adverse effects.
Innovation Solution
An orodispersible effervescent tablet formulation of budesonide, which disintegrates slowly in the mouth, releasing the drug in a prolonged manner to achieve high esophageal exposure, combining with a pharmaceutically acceptable acid to enhance pH decrease and gas release, providing sustained mucosal contact and targeted delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nebulized and swallowed corticosteroids are used, then treatment can be administered, but esophageal targeting is inadequate and remission is not maintained
Solution Approach 1:
The treatment approach is segmented into two distinct phases: induction phase using high-dose topical corticosteroids to achieve remission, and maintenance phase using low-dose therapy to sustain remission. This segmentation allows optimization of drug delivery for each phase, improving overall reliability of esophageal targeting while controlling total drug quantity.
Solution Approach 2:
The induction phase with high-dose topical corticosteroids is administered first to achieve rapid remission, creating a favorable baseline state. This preliminary action prepares the esophageal tissue for subsequent maintenance therapy, ensuring that the maintenance phase can effectively sustain the achieved remission with lower doses.
2Reliability
If systemic corticosteroids are used for long-term treatment, then remission can be maintained, but severe adverse effects occur
Solution Approach 1:
The invention employs topical corticosteroids administered directly to the esophagus rather than systemic administration. This local quality approach concentrates the therapeutic effect at the esophageal site while minimizing systemic exposure, thereby maintaining remission reliability while dramatically reducing adverse effects.
Solution Approach 2:
The treatment strategy uses short-term high-dose induction followed by long-term low-dose maintenance, analogous to using intensive initial treatment then transitioning to minimal sustainable therapy. This approach achieves reliable remission maintenance while minimizing cumulative drug exposure and associated adverse effects.
3Speed
If high dose corticosteroids are used for induction, then remission is achieved rapidly, but total drug exposure increases
Solution Approach 1:
The treatment is structured as periodic action with distinct phases: an induction phase using high doses to achieve rapid remission, followed by a maintenance phase using low doses to sustain remission. This periodic structure allows rapid initial response while controlling total cumulative drug exposure through the subsequent low-dose phase.
Solution Approach 2:
The induction phase uses excessive (high) dosing temporarily to achieve rapid remission, then transitions to partial (low) dosing for maintenance. This partial/excessive action strategy achieves the speed benefit of high-dose induction while limiting total drug exposure through the subsequent reduced-dose maintenance phase.
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 budesonide orodispersible effervescent tablets achieve deep endoscopic and histological remission, maintaining therapeutic success over extended periods, significantly improving esophageal distensibility and reducing fibrostenotic changes, with rapid onset and high remission rates compared to placebo, and minimal side effects.
Implementation Method 1
The effervescent action is caused by the salt of at least one pharmaceutically acceptable acid which in an aqueous environment, in particular in the mouth containing saliva, can release a gas which is preferably CO2 in cooperation with a further acid
Implementation Method 2
The effervescent tablet contains the salt of a further weak acid or a further weak acid that decreases the pH value in the aqueous solution
Data Source
AI summary
Orodispersible effervescent tablets comprising budesonide are administered to patients suffering from eosinophilic esophagitis whereby a complete mucosal healing (i.e., deep endoscopic AND deep histological remission) and even a deep disease remission (i.e., deep clinical AND deep endoscopic AND deep histological remission) is achieved by a treatment regimen of administering said orodispersible effervescent tablets for at least six weeks to twelve weeks for the induction period and thereafter up to three a years as maintenance treatment.