Starch-Based Release Modifying Excipients for Consistent Drug Delivery

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Solution Overview

Problem

Conventional starch-based extended release pharmaceutical dosage forms face challenges such as batch-to-batch inconsistency, inability to optimize amylose to amylopectin ratio, and limited supply, leading to inconsistent gelling speeds and release profiles, which can affect the efficacy and reliability of drug delivery.

Innovation Solution

A pharmaceutical dosage form comprising a blend of high amylose starch, cross-linked hydroxypropylated amylopectin, and pre-gelatinized common starch, where the release modifying excipient is substantially free of crosslinks between amylose and amylopectin subunits, allowing for flexible formulation and optimized release properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If cross-linked high amylose starch is used as release modifying excipient, then extended release properties are achieved, but batch-to-batch inconsistency occurs due to natural variation in amylose to amylopectin ratio

Engineering Contradiction:

Improveextended release durationVSAvoidbatch-to-batch consistency

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent changes the chemical structure parameters of the starch by introducing cross-links between amylose and amylopectin subunits through chemical modification. This cross-linking process creates a more stable molecular structure that maintains consistent gelling properties across batches, thereby improving reliability while preserving extended release duration.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite starch structure by combining cross-linked amylose and amylopectin subunits within the same molecular network. This composite approach allows the material to exhibit both the extended release properties of high amylose starch and the consistency benefits of cross-linked structures, resolving the contradiction between duration and reliability.

Inventive Principle:

Principle #40Composite materials

2Speed

If chemical modification is applied to starch to improve release properties, then gelling speed is controlled, but manufacturing complexity increases

Engineering Contradiction:

Improvegelling speedVSAvoidmanufacturing process complexity

Core Design Contradiction:

SpeedVSDevice complexity

Solution Approach 1:

The patent performs chemical modification and cross-linking of the starch before it is used in the pharmaceutical formulation. By preparing the modified starch in advance with predetermined cross-linking, the complex manufacturing steps are consolidated into a pre-processing stage, simplifying the overall formulation process while maintaining controlled gelling speed.

Inventive Principle:

Principle #10Preliminary action

3Duration of action of moving object

If high amylose starch is used to achieve extended release, then dosing frequency is reduced, but supply limitations occur

Engineering Contradiction:

Improverelease durationVSAvoidsupply availability

Core Design Contradiction:

Duration of action of moving objectVSQuantity of substance

Solution Approach 1:

The patent modifies the starch structure through cross-linking and chemical modification to enhance its functional properties. This allows the use of starch from diverse plant sources (corn, potato, pea) rather than being limited to high amylose corn starch, thereby increasing supply availability while maintaining extended release duration through the modified molecular structure.

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 dosage form achieves consistent and controlled release of active pharmaceutical ingredients, matching or exceeding the performance of conventional cross-linked high amylose starch formulations, with improved stability and reduced risk of dose dumping, even when subdivided, and maintains effective release profiles across varying pH conditions and in the presence of ethanol.

Implementation Method 1

the gelling properties of the starch-based excipients are thought to create a barrier to immediate release of the API in the gastrointestinal environment

Methodology Applied

Scientific EffectGel: Gel

Implementation Method 2

This modification is intended to limit crystallinity and increase swelling

Methodology Applied

Scientific EffectSwelling:

Data Source

PatentUS11529419B2Starch-based release modifying excipients and pharmaceutical compositions derived therefrom

Publication Date: 2022.12.20 ALTUS FORMULATION INC

AI summary

There is provide an extended release dosage form comprising a release modifying excipient comprising high amylose starch, cross-linked hydroxypropylated amylopectin, and a pre-gelatinized common starch; wherein the release modifying excipient is substantially free of crosslinks between amylose and amylopectin and substantially free of crosslinks between amylose and amylose. It has been found that the extended release properties of conventional cross-linked high amylose starches (e.g., Contramid®) can be reproduced by intimately mixing i) cross-linked chemically modified amylopectin; ii) a high amylose, non-chemically modified starch and; iii) a pre-gelatinized common starch. Producing a release modifying excipient in this way means that no chemical cross linking between (a) amylose and amylopectin or (b) amylose and amylose has occurred—properties heretofore considered vital for Contramid® function. The release modifying excipient blends overcome problems associated with use of Contramid, and provide a flexible platform for formulation of active pharmaceutical ingredients for controlled release applications.