Orlistat Powder Manufacturing Process Stability

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Solution Overview

Problem

The existing methods for manufacturing pharmaceutical compositions of Orlistat are complex, expensive, and require atypical additives, which pose technological difficulties due to its waxy character and low chemical stability, leading to challenges in achieving stable and cost-effective production.

Innovation Solution

A simplified process involving blending Orlistat with pharmaceutically acceptable additives like glidants, disintegrants, and fillers, followed by encapsulation, eliminates the need for expensive and difficult-to-handle additives, enhancing chemical stability and reducing manufacturing complexity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If extrusion and spheronisation method is used to manufacture Orlistat compositions, then the product meets quality requirements, but the manufacturing process becomes complicated, time-consuming and expensive

Engineering Contradiction:
Improveproduct qualityVSAvoidmanufacturing process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the complex extrusion and spheronisation steps from the manufacturing process. Instead of using these complicated technologies, the patent employs simple blending of Orlistat with excipients followed by direct encapsulation, thereby removing the problematic stages while maintaining product quality.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention inverts the conventional approach by not micronizing Orlistat before formulation. Instead of using micronized Orlistat as in the prior art, the patent uses unmicronized Orlistat directly in the blending step, which simplifies the process and reduces complexity while still achieving the desired product quality.

Inventive Principle:
Principle #13The other way round (Inversion)

2Reliability

If atypical pharmaceutical additives are used in Orlistat formulations, then quality requirements are met, but manufacturing costs increase and technological difficulties arise

Engineering Contradiction:
Improveproduct qualityVSAvoidmanufacturing ease
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention replaces expensive, atypical pharmaceutical additives with common, inexpensive excipients such as microcrystalline cellulose, lactose, and magnesium stearate. These standard materials are widely available, easy to handle, and significantly reduce manufacturing costs while still producing quality-compliant Orlistat compositions.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention changes the formulation parameters by using conventional excipients at optimized proportions rather than atypical additives. This parameter change simplifies manufacturing operations and reduces technological difficulties associated with handling unstable or specialized materials.

Inventive Principle:
Principle #35Parameter changes

3Area of moving object

If micronized Orlistat is used in formulations, then surface area increases, but chemical stability decreases and hydrolysis risk increases

Engineering Contradiction:
Improvesurface areaVSAvoidchemical stability
Core Design Contradiction:
Area of moving objectVSStability of the object's composition

Solution Approach 1:

The invention inverts the conventional approach by deliberately not micronizing the Orlistat. Instead of increasing surface area through micronization, the patent uses unmicronized Orlistat with larger particle size, which inherently reduces the surface area exposed to moisture and thereby improves chemical stability and reduces hydrolysis risk.

Inventive Principle:
Principle #13The other way round (Inversion)

4Shape

If wet granulation stage is performed, then granulation is achieved, but hydrolysis of Orlistat occurs due to moisture exposure

Engineering Contradiction:
ImprovegranulationVSAvoidchemical purity
Core Design Contradiction:
ShapeVSStability of the object's composition

Solution Approach 1:

The invention extracts and eliminates the wet granulation stage from the manufacturing process. Instead of performing wet granulation that exposes Orlistat to moisture and causes hydrolysis, the patent uses dry blending of ingredients followed by direct encapsulation, thereby removing the harmful moisture exposure step while still achieving proper granulation and capsule formation.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP2268266B1Process for obtaining powder compositions of orlistat to be filled into a capsule
Publication Date: 2020.10.21 ZAKLADY FARMACEUTYCZNE POLPHARMA SA
  • EP2268266B1 patent drawingFigure 1
  • EP2268266B1 patent drawingFigure 2

AI summary

The invention relates to a novel process for the manufacture of stable, meeting relevant quality requirements pharmaceutical compositions in the form of encapsulated powder comprising Orlistat and pharmaceutically acceptable additives. The invention further relates to pharmaceutical compositions of Orlistat in the form of encapsulated powder obtained in accordance with the process of the present invention.