Non-Micronized High-Load Pharmaceutical Formulation for Rapid Dissolution

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Solution Overview

Problem

Current pharmaceutical formulations of (4-chlorophenyl)[4-(4-pyridylmethyl)-phthalazin-1-yl] face challenges with solubility issues due to pH dependence, requiring immediate-release formulations for effective absorption, and traditional micronization methods are costly and problematic, leading to low patient compliance due to high dosing frequency.

Innovation Solution

Development of a non-micronized, high-load solid pharmaceutical formulation with a particle size distribution that ensures at least 70% of the drug is dissolved within 30 minutes at pH 3.0, using a formulation with a high percentage of the active ingredient and minimal excipients, allowing for efficient production and rapid release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If micronization is used to improve drug release, then dissolution rate is improved, but manufacturing complexity and cost increase

Engineering Contradiction:
Improvedissolution rateVSAvoidmanufacturing complexity
Core Design Contradiction:
SpeedVSDevice complexity

Solution Approach 1:

The patent changes the particle size parameter by defining specific ranges (d90: 50-300 μm, d50: 15-100 μm) that optimize dissolution without requiring full micronization. This parameter optimization resolves the contradiction by achieving adequate dissolution rates while avoiding the manufacturing complexity of traditional micronization processes.

Inventive Principle:
Principle #35Parameter changes

2Speed

If micronization is used to improve drug release, then dissolution rate is improved, but manufacturing cost increases

Engineering Contradiction:
Improvedissolution rateVSAvoidmanufacturing cost
Core Design Contradiction:
SpeedVSEase of manufacture

Solution Approach 1:

The patent optimizes particle size parameters to achieve effective dissolution without the high costs associated with complete micronization. The specified ranges (d90: 50-300 μm, d50: 15-100 μm) represent a cost-effective compromise that maintains therapeutic efficacy while reducing manufacturing expenses.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If high dosing frequency is used to achieve therapeutic effect, then drug efficacy is maintained, but patient compliance decreases

Engineering Contradiction:
Improvedrug efficacyVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent enables sustained therapeutic action by optimizing particle size for immediate release, allowing the drug to maintain effective concentrations over extended periods. This continuity of therapeutic effect reduces dosing frequency while maintaining efficacy, thereby improving patient compliance.

Inventive Principle:
Principle #20Continuity of useful action

4Quantity of substance

If immediate-release formulation is used to improve absorption, then bioavailability is improved, but manufacturing precision requirements increase

Engineering Contradiction:
ImprovebioavailabilityVSAvoidparticle size control
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent defines specific particle size ranges (d90: 50-300 μm, d50: 15-100 μm) that balance immediate-release performance with manufacturing feasibility. These parameter specifications enable effective absorption while maintaining reasonable manufacturing precision requirements.

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 formulation achieves a reproducible immediate-release profile with high drug load, reducing dosing frequency and manufacturing complexities, enhancing patient compliance and stability while maintaining effective drug delivery.

Implementation Method 1

at least 70% of said (4-chlorophenyl)[4-(4-pyridylmethyl)-phthalazin-l- yl], or a pharmaceutical acceptable salt thereof, is dissolved from said solid pharmaceutical formulation within 30 minutes as determined by the USP 28 Paddle Method using 0.05 M KH2PCVHCI buffer adjusted to pH 3.0 at 37°C as the dissolution media

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentEP1888072A1Immediate-release and high-drug-load pharmaceutical formulations of non-micronised (4-chlorophenyl)[4-(4-pyridylmethyl)phthalazin-1-YL]and salts thereof
Publication Date: 2008.02.20 SCHERING AG

AI summary

The invention relates to immediate-release and high-drug-load solid pharmaceutical formulations comprising non- micronized (4-chlorophenyl)[4-(4-pyridylmethyl)-phthalazin-1-yl] as well as pharmaceutically acceptable salts thereof.