Vaginal Suppository Dual-Phase Formulation

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Solution Overview

Problem

Existing vaginal suppositories with imidazole antifungal active ingredients face challenges in maintaining effective concentration and adhesion to vaginal mucosal surfaces, leading to high recurrence rates of fungal infections due to poor solubility and rapid dissolution of active ingredients, necessitating frequent administration and incomplete coverage of the vaginal area.

Innovation Solution

A vaginal suppository formulation containing a combination of dissolved and suspended antifungal active ingredients in a polyethylene-glycol and polysorbate base, where the ratio of both forms is reproducible and stable, allowing for deeper penetration and prolonged release of the active ingredient, ensuring effective coverage of the vaginal mucosal membrane.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the active ingredient is used in high doses to achieve sufficient blood concentration for treating fungal infections, then the therapeutic effect is improved, but the formulation difficulty increases and undesired side effects occur

Engineering Contradiction:
Improvetherapeutic effectVSAvoidundesired side effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses vaginal suppositories as an intermediary delivery system to provide local treatment of fungal infections. The suppository base (polyethylene-glycol with polysorbate) acts as a mediator that releases the active ingredient directly at the infection site, avoiding the need for high systemic doses and their associated side effects. This local delivery mechanism achieves therapeutic effect while minimizing harmful effects.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If the active ingredient is formulated in suspended form in oleaginous base to improve adhesion, then the adhesion to mucosal surface is improved, but the penetration into narrow folds of mucosal membrane is reduced

Engineering Contradiction:
ImproveadhesionVSAvoidcoverage area
Core Design Contradiction:
Stability of the object's compositionVSArea of stationary object

Solution Approach 1:

The patent changes the physical parameters of the suppository base by using polyethylene-glycol instead of traditional oleaginous bases. This parameter change provides both adequate adhesion and the ability to penetrate into narrow folds of the vaginal mucosa, achieving both requirements simultaneously through modification of the base material properties.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite suppository base combining polyethylene-glycol and polysorbate. This composite material integrates the adhesive properties needed for retention with the penetration capability required to reach into narrow mucosal folds, resolving the contradiction between adhesion and coverage area.

Inventive Principle:
Principle #40Composite materials

3Speed

If the active ingredient is dissolved in the suppository base for rapid effect, then the onset of action is improved, but the duration of action is reduced due to rapid dissolution

Engineering Contradiction:
Improveonset of actionVSAvoidduration of action
Core Design Contradiction:
SpeedVSDuration of action of moving object

Solution Approach 1:

The patent segments the active ingredient into two distinct forms within the suppository: dissolved and suspended portions. The dissolved fraction provides rapid onset of action by immediately available active ingredient, while the suspended fraction ensures prolonged duration by gradually releasing active ingredient over time. This segmentation resolves the contradiction between speed and duration of action.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent achieves continuous therapeutic action by combining dissolved and suspended forms of the active ingredient. The dissolved portion provides immediate effect while the suspended portion continuously releases active ingredient, ensuring uninterrupted therapeutic coverage throughout the treatment period.

Inventive Principle:
Principle #20Continuity of useful action

4Duration of action of moving object

If the suppository base is designed for sustained release to extend duration of action, then the duration is improved, but the penetration into narrow folds of mucosal membrane is reduced

Engineering Contradiction:
Improveduration of actionVSAvoidcoverage area
Core Design Contradiction:
Duration of action of moving objectVSArea of stationary object

Solution Approach 1:

The patent modifies the physical parameters of the sustained-release mechanism by using polyethylene-glycol base with specific viscosity and adhesion properties. This parameter change allows the sustained-release formulation to simultaneously penetrate into narrow vaginal folds while maintaining prolonged duration of action, overcoming the limitation of traditional sustained-release systems.

Inventive Principle:
Principle #35Parameter changes

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 dual-formulation suppository achieves enhanced therapeutic efficacy by rapid penetration and prolonged release of the active ingredient, reducing recurrence rates and improving patient convenience by maintaining effective concentrations for an extended period without the need for frequent administration.

Implementation Method 1

a vaginal suppository with improved efficacy containing an antifungal active ingredient, wherein said active ingredient is present simultaneously in dissolved and suspended form in a suppository base containing polyethylene-glycol and polysorbate

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 2

said active ingredient is present simultaneously in dissolved and suspended form

Methodology Applied
Scientific EffectSuspension: Suspension

Implementation Method 3

deeper penetration and prolonged release of the active ingredient, ensuring effective coverage of the vaginal mucosal membrane

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 4

prolonged release of the active ingredient, reducing recurrence rates and improving patient convenience by maintaining effective concentrations for an extended period

Methodology Applied
Scientific EffectProlonged release:

Data Source

PatentEP2385821B1Improved pharmaceutical formulation
Publication Date: 2016.08.31 EGIS GYOGYSZERGYAR NYILVANOSAN MUKODO RESZVENY TARSASAG
  • EP2385821B1 patent drawingFigure 1~2
  • EP2385821B1 patent drawingFigure 3~4
  • EP2385821B1 patent drawingFigure 5~6

AI summary

The subject of the invention is a vaginal suppository with improved efficacy containing an antifungal active ingredient, wherein the said active ingredient is present simultaneously in dissolved and suspended form in the suppository base containing polyethylene-glycol and polysorbate. The ratio of the suspended and dissolved active ingredient in the suppository is reproducible and said ratio does not change during the storage. A further subject of the present invention is a process for manufacturing said pharmaceutical formulations.