Bead Formulations for Overactive Bladder Dry Mouth Management

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Solution Overview

Problem

Current treatments for overactive bladder using muscarinic receptor antagonists, such as tolterodine, often cause severe dry mouth as a side effect, reducing patient compliance, and require inconvenient timing of medication administration to manage this side effect effectively.

Innovation Solution

Pharmaceutical formulations comprising beads with a muscarinic antagonist in immediate release and a muscarinic agonist like pilocarpine or cevimeline in delayed release, where the muscarinic antagonist is released immediately and the agonist is released after a delay, allowing for a single dose that synchronizes the timing of dry mouth relief with the antagonist's effect.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a muscarinic antagonist is administered to treat overactive bladder, then the therapeutic efficacy is improved, but severe dry mouth side effect occurs

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoiddry mouth side effect
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by incorporating a muscarinic agonist (pilocarpine or cevimeline) into the formulation that will be released before or concurrent with the muscarinic antagonist to preemptively stimulate saliva production and counteract the anticipated dry mouth effect, thereby maintaining therapeutic efficacy while preventing the harmful side effect

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses a muscarinic agonist as an intermediary substance that mediates between the therapeutic need for anticholinergic activity and the adverse effect of dry mouth. The agonist acts as a counterbalancing agent that stimulates salivation to offset the antagonist-induced dry mouth, allowing the antagonist to maintain its therapeutic effect on overactive bladder

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If pilocarpine and muscarinic antagonist are administered at different times to optimize dry mouth relief, then the side effect is reduced, but patient compliance decreases due to inconvenient timing

Engineering Contradiction:
Improvedry mouth side effectVSAvoidpatient compliance
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The patent merges the muscarinic agonist and muscarinic antagonist into a single combined pharmaceutical formulation, allowing both agents to be administered simultaneously in one dose. This eliminates the need for separate timing of administrations while maintaining the therapeutic benefit of counteracting dry mouth effects, thereby significantly improving patient compliance

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent segments the combined formulation into multiple beads or particles, where each bead contains either the muscarinic agonist or the muscarinic antagonist. This segmentation allows for controlled release patterns where the agonist and antagonist are released at different rates or times within the same formulation, optimizing the timing of drug delivery while maintaining a single-administration regimen

Inventive Principle:
Principle #1Segmentation

3Ease of operation

If a single formulation contains both muscarinic agonist and antagonist, then administration is simplified, but the timing of drug release must be precisely controlled

Engineering Contradiction:
Improveadministration simplicityVSAvoiddrug release timing control
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent segments the formulation into distinct beads containing either the muscarinic agonist or antagonist, with each bead type having specific release characteristics. This segmentation enables precise control over the release timing and rate of each drug component, ensuring the agonist is released to counteract dry mouth effects while the antagonist provides sustained therapeutic action

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by giving different beads different properties - some beads are designed for immediate release of the agonist, others for delayed or sustained release of the antagonist. This localized differentiation in release characteristics within the same formulation allows precise temporal control of drug delivery to optimize both efficacy and side effect management

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS10786457B2Pharmaceutical formulations
Publication Date: 2020.09.29 THERAVIDA INC

AI summary

Disclosed herein are pharmaceutical compositions comprising a plurality of first beads each comprising: a core; a first layer comprising pilocarpine or a pharmaceutically acceptable salt thereof; and a second layer comprising a first polymer. Also disclosed are pharmaceutical compositions comprising a plurality of second beads each comprising: a core; and a first layer comprising tolterodine or a pharmaceutically acceptable salt thereof. Further disclosed are pharmaceutical formulations comprising: a) a plurality of the first beads; b) a plurality of the second beads; or c) a plurality of the first beads and a plurality of the second beads.