Nasal Suspension Stabilization Using Hydrocolloids

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Solution Overview

Problem

Current treatments for rhinitis lack stability and effectiveness in maintaining a fixed dose combination of mometasone and olopatadine for nasal administration, often experiencing phase separation and instability during storage, which affects dosing consistency and patient relief.

Innovation Solution

A stable fixed dose, aqueous pharmaceutical composition comprising mometasone or its salt and olopatadine or its salt, combined with a hydrocolloid such as carboxymethylcellulose sodium or xanthan gum, which maintains a single phase suspension even after storage at varying temperatures and humidity levels, ensuring consistent delivery and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a fixed dose combination of mometasone and olopatadine is formulated for nasal administration, then effective treatment of rhinitis is achieved, but phase separation and instability occur during storage

Engineering Contradiction:
Improvestability of fixed dose combinationVSAvoidphase separation during storage
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

A hydrocolloid is introduced as an intermediary substance to stabilize the suspension and prevent phase separation between mometasone and olopatadine components during storage, maintaining the integrity of the fixed dose combination

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The formulation utilizes specific pH ranges and concentration parameters to optimize the stability of the aqueous suspension, preventing crystallization of olopatadine and maintaining uniform distribution of both active ingredients

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If the composition is stored at varying temperatures and humidity levels, then real-world storage conditions are accommodated, but dosing consistency deteriorates

Engineering Contradiction:
Improvestorage condition toleranceVSAvoiddosing consistency
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The hydrocolloid and buffer system are formulated in advance to cushion against the effects of temperature and humidity variations during storage, preventing changes in viscosity and phase separation that would compromise dosing consistency

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Ease of operation

If olopatadine is formulated in aqueous solution, then ease of administration is improved, but crystallization occurs during storage

Engineering Contradiction:
Improveease of nasal administrationVSAvoidcrystallization of olopatadine
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The pH of the aqueous formulation is carefully adjusted to a specific range that prevents crystallization of olopatadine while maintaining its solubility and stability, allowing the formulation to remain in a stable liquid state during storage

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The formulation combines olopatadine with hydrocolloid and other excipients to create a composite aqueous suspension that prevents crystallization while maintaining ease of nasal administration

Inventive Principle:
Principle #40Composite materials

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 remains stable and effective, providing consistent dosing of mometasone and olopatadine, maintaining therapeutic benefits for rhinitis treatment with improved stability and reduced crystallization of olopatadine, ensuring effective symptom relief.

Implementation Method 1

the composition is in the form of a suspension (more preferably, a single phase suspension), wherein mometasone or its salt is present in particle form and olopatadine or its salt is present in dissolved form

Methodology Applied
Scientific EffectSuspension: Suspension

Implementation Method 2

combined with a hydrocolloid such as carboxymethylcellulose sodium or xanthan gum, which maintains a single phase suspension even after storage

Methodology Applied
Scientific EffectHydrocolloid: Hydrogel

Data Source

PatentUS10765686B2Stable fixed dose pharmaceutical composition comprising mometasone and olopatadine
Publication Date: 2020.09.08 GLENMARK SPECIALTY

AI summary

The present invention relates to a stable fixed dose aqueous pharmaceutical composition (e.g., contained in a container) for nasal administration to a human, comprising mometasone or its salt, olopatadine or its salt. The composition may further include a hydrocolloid. The invention also relates to a process for preparing the pharmaceutical composition, and the use of the pharmaceutical composition in the treatment of rhinitis in a subject.