Ivabradine Solid Oral Composition for Polymorphic Stability

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Solution Overview

Problem

Existing pharmaceutical compositions of ivabradine hydrochloride face challenges with content uniformity, stability, and polymorphic transitions, leading to issues with dissolution profiles and bioavailability.

Innovation Solution

The formulation of solid oral pharmaceutical compositions using ivabradine hydrochloride with specific ratios of microcrystalline cellulose to lactose, combined with film-coating of a certain thickness, along with suitable excipients like sodium stearyl fumarate and colloidal silicon dioxide, to enhance stability and content uniformity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If high amount of excipients is used to improve content uniformity and flowability, then manufacturing precision is improved, but polymorphic transformation and degradation of ivabradine increase

Engineering Contradiction:

Improvecontent uniformityVSAvoidpolymorphic stability

Core Design Contradiction:

Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by precisely controlling the ratio of microcrystalline cellulose to lactose (more than 1.00 by weight) and optimizing the overall excipient content. This specific parameter adjustment resolves the contradiction by achieving adequate content uniformity and flowability while minimizing the excipient amount that could induce polymorphic transformation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite excipient system combining microcrystalline cellulose and lactose in a specific ratio, rather than using单一 excipient. This composite approach allows the formulation to achieve both good manufacturing precision (content uniformity) and polymorphic stability by leveraging the complementary properties of both excipients.

Inventive Principle:

Principle #40Composite materials

2Manufacturing precision

If mechanical stress is applied during processing to improve manufacturing precision, then content uniformity is improved, but polymorphic transformation increases

Engineering Contradiction:

Improvecontent uniformityVSAvoidpolymorphic stability

Core Design Contradiction:

Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent applies beforehand cushioning by pre-optimizing the excipient composition (microcrystalline cellulose to lactose ratio > 1.00) to create a formulation that is inherently resistant to polymorphic transformation. This pre-protection allows the application of necessary mechanical stress during processing to achieve content uniformity without triggering degradation.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

3Reliability

If excipients are used to improve dissolution profile, then bioavailability is improved, but polymorphic transformation is induced

Engineering Contradiction:

ImprovebioavailabilityVSAvoidpolymorphic stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent resolves this contradiction by changing the parameters of excipient selection and ratio. By using microcrystalline cellulose and lactose in a specific ratio (>1.00 by weight), the formulation achieves improved dissolution profile and bioavailability while the controlled excipient amount prevents polymorphic transformation.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP3366282B1Solid oral pharmaceutical compositions of ivabradine

Publication Date: 2025.10.01 SANOVEL ILAC SANAYI & TICARET ANONIM SIRKETI

AI summary

The present invention relates to solid oral pharmaceutical compositions, comprising ivabradine hydrochloride or pharmaceutically acceptable polymorphs thereof and at least one cellulose derivative excipient.