Annealing Amorphous Atorvastatin for Stability

Solution Overview

Problem

Amorphous atorvastatin exhibits lower physical and chemical stability compared to crystalline forms, leading to reduced shelf life and susceptibility to degradation, which affects its medical usability.

Innovation Solution

Annealing amorphous atorvastatin through heating at elevated temperatures, applying high pressure, or using microwave or ultrasound irradiation to enhance its stability, thereby reducing chemical degradation and extending its storage duration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If amorphous atorvastatin is used to achieve rapid dissolution and high bioavailability, then dissolution rate and bioavailability are improved, but physical and chemical stability deteriorates

Engineering Contradiction:

Improvedissolution rateVSAvoidphysical and chemical stability

Core Design Contradiction:

SpeedVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary annealing treatment to amorphous atorvastatin before formulation to stabilize its molecular structure. By heating the amorphous material to specific temperatures (e.g., 50-150°C) and holding it for defined periods, the molecular arrangement is pre-optimized to reduce subsequent degradation during storage, thus preventing future stability problems while maintaining the amorphous state's dissolution advantages

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent changes physical parameters (temperature, time, pressure) during annealing treatment to transform the amorphous atorvastatin's internal structure. By controlling annealing temperature ranges and durations, the molecular mobility and free volume are adjusted, resulting in improved stability without converting to crystalline form, thereby resolving the contradiction between amorphous state benefits and stability

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If amorphous atorvastatin is used to achieve rapid onset of activity, then therapeutic efficacy is improved, but shelf life deteriorates

Engineering Contradiction:

Improveonset of activityVSAvoidshelf life

Core Design Contradiction:

Duration of action of moving objectVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary annealing treatment to amorphous atorvastatin before formulation to stabilize its molecular structure. By heating the amorphous material to specific temperatures (e.g., 50-150°C) and holding it for defined periods, the molecular arrangement is pre-optimized to reduce subsequent degradation during storage, thus preventing future stability problems while maintaining the amorphous state's dissolution advantages

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent changes physical parameters (temperature, time, pressure) during annealing treatment to transform the amorphous atorvastatin's internal structure. By controlling annealing temperature ranges and durations, the molecular mobility and free volume are adjusted, resulting in improved stability without converting to crystalline form, thereby resolving the contradiction between amorphous state benefits and stability

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

Annealed amorphous atorvastatin demonstrates improved stability, allowing for longer storage and the creation of pharmaceutical dosage forms with enhanced stability profiles compared to non-annealed samples.

Implementation Method 1

Annealing amorphous atorvastatin through heating at elevated temperatures

Methodology Applied

Scientific EffectAnnealing: Annealing

Implementation Method 2

heating at ambient pressure amorphous atorvastatin in an essentially solvent-free system to a temperature of between approximately 50° C. to approximately 140° C.

Methodology Applied

Scientific EffectHeating: Heating

Implementation Method 3

applying high pressure

Methodology Applied

Scientific EffectHigh pressure: Pressurisation

Implementation Method 4

using microwave or ultrasound irradiation

Methodology Applied

Scientific EffectMicrowave irradiation: Microwave Radiation

Implementation Method 5

using microwave or ultrasound irradiation

Methodology Applied

Scientific EffectUltrasound: Ultrasound

Data Source

PatentUS9932307B2Process for annealing amorphous atorvastatin

Publication Date: 2018.04.03 UPJOHN US 1 LLC

AI summary

Processes for annealing amorphous atorvastatin is described. Pharmaceutical compositions and formulations containing annealed amorphous atorvastatin are also described.