Brimonidine Pamoate Polymorphs Sustained Release Glaucoma

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current brimonidine formulations for treating glaucoma and providing neuroprotection to the optic nerve system have limitations, including rapid clearance from the eye and instability in ocular environments, which affects their sustained release and effectiveness.

Innovation Solution

Development of stable polymorphs of brimonidine pamoate, specifically Forms A, B, C, D, E, and F, characterized by distinct XRPD and Raman spectroscopy spectra, which provide a sustained release and enhanced stability in ocular environments, allowing for effective neuroprotection and reduced intraocular pressure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If brimonidine tartrate is used to increase solubility, then solubility is improved, but the drug is rapidly cleared from the eye and cannot provide sustained release

Engineering Contradiction:

ImprovesolubilityVSAvoidduration of action

Core Design Contradiction:

Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The invention changes the chemical parameter by converting brimonidine tartrate to brimonidine pamoate, which has different solubility and release characteristics. The pamoate salt provides both adequate solubility and sustained release capability, resolving the contradiction between solubility and duration of action.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If intravitreal injection is performed frequently to maintain therapeutic effect, then therapeutic effectiveness is improved, but unnecessary disturbance of the eye increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoiddisturbance to the eye

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention uses a sustained-release formulation that provides prolonged therapeutic effect from a single injection, eliminating the need for frequent administrations. The brimonidine pamoate polymorphs release the drug slowly over time, maintaining therapeutic effectiveness while minimizing disturbance to the eye.

Inventive Principle:

Principle #16Partial or excessive action

3Reliability

If brimonidine is used for neuroprotection, then neuroprotective effect is achieved, but instability in ocular environments reduces effectiveness

Engineering Contradiction:

Improveneuroprotective effectVSAvoidstability in ocular environment

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention creates composite crystalline structures by forming brimonidine pamoate salts with specific polymorphic forms. These composite materials combine the neuroprotective properties of brimonidine with enhanced stability in ocular environments, ensuring both neuroprotective effect and stability.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS8637515B2Polymorphs of brimonidine pamoate

Publication Date: 2014.01.28 BAUSCH & LOMB INC

AI summary

A polymorph of brimonidine pamoate having the formulaexhibits characteristics disclosed herein. The polymorph is included in a composition, device, or implant for use in the treatment or control of elevated intraocular pressure or in the neuroprotection of components of a neurological tissue to prevent progressive degeneration of such components. In particular, such a composition, device, or implant can be used to provide neuroprotection to cells and components of the optic nerve system.