Zonisamide ODT Formulation Strength Disintegration

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Solution Overview

Problem

Current methods for producing orally disintegrating tablets (ODTs) of zonisamide face challenges in achieving high mechanical resistance while maintaining quick disintegration times, often requiring complex and energy-intensive processes, and using non-standard excipients that increase costs and complexity.

Innovation Solution

The development of ODTs using direct compression with a formulation comprising zonisamide, mannitol, microcrystalline cellulose, carmellose, crospovidone, and a lubricant, which provides high hardness and rapid disintegration, and can be manufactured using simple machinery with lower economic and energetic costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional compaction technologies with superdisintegrants are used, then disintegration is accelerated, but tablet mechanical resistance decreases

Engineering Contradiction:
Improvedisintegration rateVSAvoidtablet mechanical resistance
Core Design Contradiction:
SpeedVSStrength

Solution Approach 1:

The patent uses a composite granule formulation containing multiple excipients (microcrystalline cellulose, crospovidone, mannitol, povidone) that work synergistically to provide both mechanical strength and rapid disintegration. The granules are compressed into tablets that maintain high mechanical resistance while achieving disintegration times under 30 seconds, resolving the contradiction between strength and disintegration rate.

Inventive Principle:
Principle #40Composite materials

2Speed

If freeze drying technology is used, then quick disintegration is achieved, but manufacturing complexity and cost increase

Engineering Contradiction:
Improvedisintegration timeVSAvoidmanufacturing process complexity
Core Design Contradiction:
SpeedVSDevice complexity

Solution Approach 1:

The patent extracts the disintegration function from the manufacturing process itself and incorporates it into the tablet formulation through the granule composition. Instead of using freeze drying to create porous structures, the patent uses chemically bonded granules with inherent disintegration properties that achieve rapid disintegration through conventional compression, eliminating complex freeze drying equipment.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces expensive freeze drying technology with conventional compression technology using specially formulated granules. The granules are designed to be compressed directly into tablets that disintegrate rapidly, using simple, widely available equipment rather than specialized freeze drying machinery, thereby reducing manufacturing complexity and cost.

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

3Strength

If RACTAB technology with multiple excipients is used, then tablet hardness is improved, but manufacturing time and energy consumption increase

Engineering Contradiction:
Improvetablet hardnessVSAvoidmanufacturing cycle time
Core Design Contradiction:
StrengthVSLoss of time

Solution Approach 1:

The patent merges multiple functions into a single granulation step. The granules contain microcrystalline cellulose for structural integrity, crospovidone for disintegration, and mannitol for hardness enhancement, all incorporated together rather than through sequential processing steps. This unified approach achieves high tablet hardness and rapid disintegration in one manufacturing pass, reducing time and energy consumption.

Inventive Principle:
Principle #5Merging (Combining)

4Speed

If molding technology is used, then rapid dissolution is achieved, but tablet mechanical resistance decreases

Engineering Contradiction:
Improvedissolution rateVSAvoidtablet mechanical resistance
Core Design Contradiction:
SpeedVSStrength

Solution Approach 1:

The patent changes the physical parameters of the granules, specifically their size distribution (D10: 30-50 μm, D50: 70-90 μm, D90: 100-150 μm) and composition, to achieve both rapid dissolution and high mechanical resistance. The controlled particle size and chemical bonding in the granules enable fast dissolution while the compression process creates tablets with adequate hardness, resolving the contradiction between dissolution rate and mechanical strength.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP4061328B1Zonisamide orodispersible tablets
Publication Date: 2024.01.03 NOUCOR HEALTH SA

AI summary

The present invention relates to solid pharmaceutical formulations comprising zonisamide as an active ingredient, in particular it relates to a tablet for oral administration of zonisamide which disintegrates rapidly in the oral cavity, has good mechanical strength properties and is obtainable by conventional manufacturing methods.