Amorphous Solid Dispersion for HCV Protease and NS5A Inhibitors

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Solution Overview

Problem

Current treatments for hepatitis C virus (HCV) infection, such as those using peginterferon-alpha and ribavirin, suffer from substantial limitations in efficacy and tolerability, with incomplete viral elimination and significant side effects, necessitating the development of new drugs.

Innovation Solution

The development of solid pharmaceutical compositions comprising potent HCV protease inhibitors (Compound 1) and NS5A inhibitors (Compound 2) in amorphous solid dispersions, formulated with pharmaceutically acceptable salts and excipients, which can be combined in various forms like tablets or mini-tablets, and administered with food to enhance bioavailability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peginterferon-alpha and ribavirin are used to treat HCV infection, then viral elimination is achieved, but side effects increase and efficacy is limited

Engineering Contradiction:

Improveviral elimination efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters by introducing new compounds with different molecular structures (Compound 1 with protease inhibitor mechanism, Compound 2 with NS5A inhibitor mechanism) that have improved therapeutic indices, reducing side effects while maintaining or enhancing viral elimination efficacy

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses composite formulation by combining Compound 1 and Compound 2 in a single pharmaceutical composition, creating a synergistic effect that improves overall treatment efficacy while allowing for reduced individual dosages and minimized side effects

Inventive Principle:

Principle #40Composite materials

2Reliability

If new HCV treatment compounds are developed, then treatment effectiveness is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent merges Compound 1 and Compound 2 into a single combined pharmaceutical composition that can be administered as one dosage form, simplifying the manufacturing process compared to producing and coordinating multiple separate medications, while maintaining the dual-mechanism treatment effectiveness

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

These compositions provide improved bioavailability and effectiveness in treating HCV infection by ensuring complete release of the compounds, thereby addressing the limitations of existing treatments and enhancing treatment outcomes.

Implementation Method 1

comprising: Compound 1 or a pharmaceutically acceptable salt thereof, formulated in amorphous solid dispersion, and Compound 2 or a pharmaceutically acceptable salt thereof, formulated in amorphous solid dispersion

Methodology Applied

Scientific EffectAmorphous solid dispersion:

Data Source

PatentUS11246866B2Solid pharmaceutical compositions for treating HCV

Publication Date: 2022.02.15 ABBVIE INC

AI summary

The present invention features solid pharmaceutical compositions comprising Compound 1 and Compound 2. In one embodiment, the solid pharmaceutical composition includes (1) a first layer which comprises 100 mg Compound 1, as well as a pharmaceutically acceptable hydrophilic polymer and a pharmaceutically acceptable surfactant, all of which are formulated in amorphous solid dispersion; and (2) a second layer which comprises 40 mg Compound 2, as well as a pharmaceutically acceptable hydrophilic polymer and a pharmaceutically acceptable surfactant, all of which are formulated in amorphous solid dispersion.