Entacapone Granule Size Reduction for Swallowability and Uniformity
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Solution Overview
Problem
Current oral dosage forms of entacapone, particularly for late-stage Parkinson's disease patients with swallowing difficulties, face challenges due to poor solubility and absorption issues, leading to manufacturing complexities and variability in content uniformity.
Innovation Solution
Development of an oral dosage form with entacapone particles of reduced size, specifically less than 55 µm, and formulations that include binders, disintegrants, and solubility enhancers to improve absorption and manufacturing efficiency, while maintaining high content uniformity and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If entacapone is formulated in traditional oral dosage forms, then the drug can be administered to patients, but patients with swallowing difficulties experience difficulty swallowing and absorption is poor
Solution Approach 1:
The patent divides the traditional tablet into smaller granules with specific size ranges (0.1-1.0 mm, preferably 0.2-0.5 mm). This segmentation makes the dosage form easier to swallow while maintaining adequate surface area for absorption. The granules can be further divided into multiple smaller units that are less burdensome for patients with dysphagia.
Solution Approach 2:
The patent changes the physical parameter of particle size from traditional tablet dimensions to granules in the 0.1-1.0 mm range. This parameter change improves swallowability while the patent maintains content uniformity through controlled granulation processes, ensuring reliable absorption despite the size reduction.
2Ease of operation
If entacapone particles are reduced in size to improve swallowing, then swallowability improves, but manufacturing complexity increases and content uniformity becomes harder to control
Solution Approach 1:
The patent specifies precise granule size parameters (0.1-1.0 mm, preferably 0.2-0.5 mm) that balance swallowability with manufacturability. These defined parameters enable standard pharmaceutical manufacturing equipment to produce consistent granules while maintaining content uniformity, avoiding excessive manufacturing complexity.
Solution Approach 2:
The patent employs fluidized bed granulation technology that uses air flow (pneumatics) to suspend and coat particles uniformly. This method achieves consistent granule formation and content uniformity through controlled fluid dynamics, simplifying the manufacturing process compared to traditional methods while producing swallowable granule sizes.
3Productivity
If entacapone is formulated with high drug content to reduce dosage frequency, then treatment efficiency improves, but content uniformity becomes more difficult to maintain
Solution Approach 1:
The patent segments the total drug content into multiple granules, each containing a manageable amount of entacapone. This segmentation allows each granule to maintain good content uniformity while the patient receives the full therapeutic dose through multiple granules, thereby preserving treatment efficiency without compromising manufacturing precision.
Solution Approach 2:
Fluidized bed granulation uses controlled air flow to ensure uniform distribution of the active ingredient throughout the granule mass. This pneumatic process achieves excellent content uniformity (CV < 6%) even in high-dose formulations, enabling both high treatment efficiency and manufacturing precision.
Data Source
Figure 1
AI summary
The present invention relates to an oral dosage form of entacapone and to methods for the preparation thereof.