Latanoprost Formulation with Sulfoalkyl Ether Cyclodextrin

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Solution Overview

Problem

Latanoprost formulations face issues with photolytic and thermal/hydrolytic degradation, and the preservative benzalkonium chloride can cause corneal damage, limiting their stability and safety.

Innovation Solution

Incorporating sulfoalkyl ether cyclodextrin (SAE-CD) into aqueous compositions with latanoprost to enhance stability and solubility, while excluding benzalkonium chloride, thereby improving formulation stability and safety.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If benzalkonium chloride is used as a preservative in latanoprost formulation, then microbial growth is inhibited, but corneal damage occurs

Engineering Contradiction:

Improvemicrobial growth inhibitionVSAvoidcorneal damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes benzalkonium chloride from the formulation entirely and replaces it with sulfur-containing compounds (such as sodium sulfite, sodium bisulfite, or sulfuric acid) that provide microbial preservation without corneal damage. This extraction of the harmful substance while maintaining the protective function resolves the contradiction between microbial inhibition and corneal safety.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical composition parameter by substituting the preservative mechanism from quaternary ammonium compounds (benzalkonium chloride) to sulfur-based compounds. This parameter change maintains the preservative effect while eliminating the harmful corneal damage effect, as sulfur-containing compounds do not exhibit the same cytotoxic properties.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If latanoprost is stored in aqueous solution, then therapeutic activity is maintained, but photolytic and thermal degradation occurs

Engineering Contradiction:

Improvetherapeutic activityVSAvoidphotolytic and thermal degradation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces sulfur-containing compounds as intermediary substances that act as antioxidants and stabilizers. These compounds mediate between the latanoprost and degrading factors (light and heat) by scavenging free radicals and preventing oxidative degradation pathways, thereby maintaining therapeutic activity while improving stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical environment parameters by adjusting pH (using sulfuric acid or sulfurites to achieve pH 4-6) and adding sulfur-containing stabilizing agents. These parameter changes create a protective chemical environment that reduces photolytic and thermal degradation rates while preserving latanoprost's therapeutic activity.

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 use of SAE-CD significantly reduces photolytic and hydrolytic degradation of latanoprost, extending shelf-life and ensuring the composition's stability and safety for ophthalmic use, without the risks associated with benzalkonium chloride.

Implementation Method 1

Reversible, non-covalent, complexation of drugs with CAPTISOL® generally allows for increased solubility and, in some cases, increased stability of drugs in aqueous solutions.

Methodology Applied

Scientific EffectComplexation:

Implementation Method 2

Latanoprost has been demonstrated to undergo substantial UV-B (320 nm to 290 nm) catalyzed photolytic degradation even under short exposure time

Methodology Applied

Scientific EffectPhotolytic degradation: Photodissociation

Implementation Method 3

it has been demonstrated to undergo substantial thermal and/or hydrolytic degradation at elevated temperatures in a pH dependent manner

Methodology Applied

Scientific EffectHydrolytic degradation: Hydrolysis

Data Source

PatentUS11433082B2Composition containing sulfoalkyl ether cyclodextrin and latanoprost

Publication Date: 2022.09.06 CYDEX PHARMACEUTICALS INC

AI summary

An aqueous composition of latanoprost and SAE-CD is provided. The composition possesses improved stability over otherwise similar compositions excluding SAE-CD. Methods of and systems for treating disease, disorders, conditions or symptoms of the eye that are therapeutically responsive to latanoprost are also provided.