Deutetrabenazine Multiparticulate Dosage Forms for Once-Daily Dosing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current deutetrabenazine dosage forms require twice-daily administration to maintain therapeutic plasma concentrations, leading to inconvenient dosing regimens and potential side effects, while existing formulations fail to provide a controlled release that sustains effective drug levels over an extended period.

Innovation Solution

Development of controlled release multiparticulate dosage forms comprising sustained release beads coated with pH-independent and pH-dependent polymers, combined with immediate release beads, to achieve once-daily administration of deutetrabenazine, ensuring consistent drug release and minimizing side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If controlled release multiparticulate dosage forms are developed, then dosing frequency can be reduced to once-daily, but formulation complexity increases

Engineering Contradiction:

Improvedosing frequencyVSAvoidformulation complexity

Core Design Contradiction:

Loss of timeVSDevice complexity

Solution Approach 1:

The dosage form is segmented into multiple bead types (sustained release beads with pH-dependent polymer coatings and immediate release beads) that are combined in a single capsule. This segmentation allows different release profiles to be achieved simultaneously, enabling once-daily dosing while managing formulation complexity through modular design

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention uses composite materials by combining pH-dependent polymer coatings (such as Eudragit® L30D-55 or S100) with deutetrabenazine on bead surfaces. This composite approach creates controlled release properties that sustain therapeutic levels throughout the day, reducing dosing frequency to once daily

Inventive Principle:

Principle #40Composite materials

2Duration of action of moving object

If sustained release beads with pH-dependent polymer coatings are used, then drug release is controlled over extended period, but manufacturing complexity increases

Engineering Contradiction:

Improveduration of drug releaseVSAvoidmanufacturing complexity

Core Design Contradiction:

Duration of action of moving objectVSEase of manufacture

Solution Approach 1:

The invention utilizes parameter changes by selecting pH-dependent polymer coatings that dissolve at specific pH ranges (e.g., pH 6.8-7.0 in intestinal conditions). This parameter-based control allows the drug to be released over an extended period (12-24 hours) as the beads traverse the gastrointestinal tract, extending duration of action while using well-established coating technologies

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The pH-dependent polymer coating acts as an intermediary layer between the deutetrabenazine core and the gastrointestinal environment. This intermediary controls the release kinetics by dissolving at specific pH levels, extending the duration of drug release while simplifying manufacturing through a straightforward coating process

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If immediate release beads are combined with sustained release beads, then consistent drug release is achieved, but dosage form complexity increases

Engineering Contradiction:

Improveconsistency of drug releaseVSAvoiddosage form complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention merges immediate release beads and sustained release beads into a single multiparticulate dosage form (capsule). This combination ensures consistent drug release by providing both rapid initial release (from immediate release beads) and prolonged release (from sustained release beads), achieving reliable therapeutic levels while maintaining a unified dosage form

Inventive Principle:

Principle #5Merging (Combining)

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 controlled release dosage forms provide a pharmacokinetic profile comparable to twice-daily AUSTEDO® administration, allowing for once-daily deutetrabenazine administration while maintaining therapeutic effects and reducing side effects, with improved drug release profiles in varying gastrointestinal pH conditions.

Implementation Method 1

the sustained release beads comprise a core comprising an amount of deutetrabenazine and a pharmaceutically acceptable excipient, and further comprising a pH-independent polymer coat, a pH-dependent polymer coat or a pH-independent polymer coat further coated with a pH-dependent polymer coat

Methodology Applied

Scientific EffectpH-dependent dissolution:

Data Source

PatentUS20230364075A1Multiparticulate dosage forms comprising deutetrabenazine

Publication Date: 2023.11.16 AUSPEX PHARMA INC

AI summary

Provided herein are controlled release multiparticulate dosage forms containing deutetrabenazine for use in the treatment of, e.g., hyperkinetic movement disorders. When orally administered to a subject on a once-daily basis, the dosage forms provide a favorable pharmacokinetic profile.