Quick Dissolving Amoxicillin Tablet Stability

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Solution Overview

Problem

Oral suspensions of amoxicillin and clavulanic acid face chemical instability, particularly at higher temperatures, leading to uneven dosing and the need for refrigeration, which complicates storage and patient compliance.

Innovation Solution

A quick-dissolving pharmaceutical formulation comprising 35-50% amoxicillin, 2-12% clavulanic acid, 30-40% mannitol, 2-7% crospovidone, 0.5-2% colloidal silicon dioxide, and 2-5% sodium stearyl fumarate, with optional silicified microcrystalline cellulose, providing improved stability and rapid solubility in minimal water.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If oral suspension is used for amoxicillin and clavulanic acid, then the medication can be administered to patients unable to swallow tablets, but the chemical stability of clavulanic acid decreases significantly, requiring refrigeration and resulting in uneven dosing

Engineering Contradiction:
Improveadministerability to patients unable to swallowVSAvoidchemical stability of clavulanic acid
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state parameter of the dosage form from liquid suspension to solid quick-dissolving tablet. This parameter change fundamentally alters the stability characteristics, allowing the medication to maintain clavulanic acid stability without refrigeration while still being easily administrable to patients who cannot swallow tablets, as the tablet rapidly dissolves in oral fluid

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite excipient system containing mannitol, crospovidone, colloidal silicon dioxide, and sodium stearyl fumarate. This composite material structure provides both the rapid dissolution properties needed for ease of administration and the structural integrity to maintain chemical stability of clavulanic acid at ambient temperatures

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If oral suspension is refrigerated for storage, then the chemical stability of active ingredients is improved, but portability and patient compliance decrease due to inconvenience

Engineering Contradiction:
Improvechemical stability of active ingredientsVSAvoidportability and patient compliance
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent changes the storage temperature parameter requirement from refrigerated (2-8°C) to ambient temperature stable. The quick-dissolving tablet formulation maintains clavulanic acid stability at ambient temperatures through the solid matrix structure and excipient system, eliminating the need for refrigeration and thereby improving portability and patient compliance without compromising stability

Inventive Principle:
Principle #35Parameter changes

3Reliability

If excess amounts of active ingredients are added to oral suspension, then adequate assay is maintained during use period, but manufacturing cost increases and dosing accuracy decreases

Engineering Contradiction:
Improveadequate assay maintenanceVSAvoiddosing accuracy
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the dosage form parameter from liquid suspension to solid tablet, which fundamentally improves dosing accuracy. Each tablet contains a precisely defined amount of active ingredients determined during manufacturing, eliminating the variable dosing that occurs in suspensions where ingredient concentration changes over time. This ensures accurate dosing without requiring excess ingredient addition

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 formulation maintains at least 85% clavulanic acid stability after 7 days at 60°C, 95% after 30 days at 40°C/75% humidity, and 98% after 90 days at 25°C/60% humidity, ensuring consistent dosing and convenient storage without refrigeration.

Implementation Method 1

The formulation maintains rapid solubility in minimal water... the pharmaceutical formulation is preferably a tablet capable of being solubilized in 5 milliliters of water

Methodology Applied
Scientific EffectSolvation: Solvation

Data Source

PatentEP3113758B1Stable quick dissolving dosage form comprising amoxicillin and clavulanic acid
Publication Date: 2019.07.03 SANDOZ LTD

AI summary

A quick dissolving pharmaceutical formulation is disclosed. In one embodiment, the formulation includes at least the following components: (1) from about 35 to about 50 weight percent amoxicillin or a pharmaceutically acceptable salt thereof; (2) from about 2.0 to about 12 weight percent clavulanic acid or a pharmaceutically acceptable salt thereof; (3) from about 30 to about 40 weight percent mannitol; (4) from about 2 to about 7 weight percent crospovidone; (5) from about 0.5 to about 2.0 weight percent colloidal silicon dioxide; and (6) from about 2.0 to about 5.0 weight percent sodium stearyl fumarate. A method for making a quick dissolving pharmaceutical tablet is also disclosed.