Deutetrabenazine Solid Dosage Formulation with Optimized Particle Size

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Formulating deutetrabenazine into solid oral dosage forms like tablets is challenging due to dissolution issues, compressibility problems, manufacturing process selection, and product degradation, necessitating a simple, reproducible, and cost-effective manufacturing process that ensures stability and bioequivalence at an industrial scale.

Innovation Solution

A solid pharmaceutical composition comprising deutetrabenazine with specific ratios of rate-controlling polymers like hypromellose and xanthan gum, binders such as povidone, and excipients like mannitol and magnesium stearate, optimized for particle size distribution and bulk density, which results in improved stability and dissolution profiles, and is bioequivalent to commercially available tablets.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional formulations of deutetrabenazine are used, then the drug can be manufactured, but dissolution issues and product degradation occur

Engineering Contradiction:

Improvedissolution profileVSAvoidproduct degradation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the particle size parameter of deutetrabenazine to a specific range (D10: 148-158 μm, D50: 188-198 μm, D90: 238-248 μm) and modifies the formulation composition parameters (rate-controlling polymer 2-10%, binder 1-10%, lubricant 0.1-2%) to achieve both improved dissolution profile and enhanced stability, resolving the contradiction between dissolution and degradation

Inventive Principle:

Principle #35Parameter changes

2Reliability

If complex formulation strategies are employed to improve dissolution, then dissolution profile improves, but manufacturing complexity increases

Engineering Contradiction:

Improvedissolution profileVSAvoidmanufacturing process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary particle size reduction and classification of deutetrabenazine to the specified D10-D50-D90 range before formulation, and pre-determines the optimal excipient ratios. This preliminary preparation simplifies the subsequent manufacturing process while ensuring consistent dissolution profile and bioequivalence

Inventive Principle:

Principle #10Preliminary action

3Reliability

If particle size is reduced to improve dissolution, then dissolution rate improves, but compressibility and manufacturing issues arise

Engineering Contradiction:

Improvedissolution rateVSAvoidcompressibility

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent optimizes the particle size parameters to a specific range (D10: 148-158 μm, D50: 188-198 μm, D90: 238-248 μm) that balances dissolution rate improvement with adequate compressibility for tablet manufacturing, and adjusts excipient ratios to facilitate proper compression and manufacturing

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11969413B2Pharmaceutical compositions of deutetrabenazine and process for preparation thereof

Publication Date: 2024.04.30 AUROBINDO PHARMA LTD

AI summary

This present invention relates to pharmaceutical composition comprising Deutetrabenazine. The invention also relates to the methods of preparation of the composition having improved stability and dissolution profile and used for the treatment of chorea associated with Huntington disease and tardive dyskinesia.