Nitrocatechol Derivative Formulations for Stability and Flow

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Solution Overview

Problem

Nitrocatechol derivatives used as COMT inhibitors are sensitive to excipients, leading to decomposition and stability issues, and exhibit low bulk density and poor flow characteristics, complicating the formulation and manufacturing of stable dosage forms.

Innovation Solution

Development of stable compositions and formulations comprising a nitrocatechol derivative in granular form, with a bulk density greater than 0.5 g/mL, using a filler that is not a phosphate derivative and a binder that is not a PVP derivative, which improves granule properties and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nitrocatechol derivatives are used as COMT inhibitors, then therapeutic efficacy is improved, but stability deteriorates due to sensitivity to excipients causing decomposition

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidstability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces specific excipients as intermediaries to protect the nitrocatechol derivative from decomposition. These excipients act as mediators between the API and the formulation environment, preventing direct harmful interactions while maintaining therapeutic efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies formulation parameters by selecting specific excipients and concentrations that change the chemical environment. This alters the stability parameters of the nitrocatechol derivative, preventing decomposition while preserving therapeutic activity.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If nitrocatechol derivatives are used as COMT inhibitors, then therapeutic efficacy is improved, but manufacturing difficulty increases due to low bulk density and poor flow characteristics

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidease of manufacture

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses granulation agents as intermediaries to improve the physical properties of the nitrocatechol derivative. These agents facilitate granulation, improving bulk density and flow characteristics without affecting therapeutic efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes physical parameters through granulation processes, transforming the API from a fine powder with poor flow to granulated form with improved bulk density and flow characteristics, making manufacturing easier while preserving therapeutic activity.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP2413913B1Pharmaceutical formulations comprising nitrocatechol derivatives and methods of making the same

Publication Date: 2022.05.18 BIAL PORTELA & CA SA

AI summary

The present disclosure relates to compositions and pharmaceutical formulations comprising at least one active pharmaceutical ingredient chosen from nitrocatechol derivatives of formula I as defined herein and salts, esters, hydrates, solvates and other derivatives thereof and methods of making the same.