Modified Release Pellets for Doxylamine Pyridoxine Homogeneity

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Solution Overview

Problem

Current multiple unit oral dosage forms of doxylamine succinate and pyridoxine hydrochloride lack inter-pellet homogeneity, affecting the dissolution profile and dosification uniformity, leading to compromised therapeutic efficacy and increased production costs.

Innovation Solution

The development of modified release multiple unit oral dosage forms using pharmaceutically acceptable inert nuclei with specific particle size ranges (300 µm to 1700 µm and variability not exceeding 200 µm) to ensure high inter-pellet homogeneity and uniform dosification, minimizing aggregate formation and reducing production costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If modified release oral dosage forms are used to provide prolonged therapeutic effect, then duration of action is improved, but inter-pellet homogeneity deteriorates affecting dissolution profile

Engineering Contradiction:

Improveduration of therapeutic effectVSAvoidinter-pellet homogeneity

Core Design Contradiction:

Duration of action of moving objectVSManufacturing precision

Solution Approach 1:

The patent divides the dosage form into multiple individual pellets (at least 10 pellets per capsule) instead of using a single compressed tablet. Each pellet is individually formed with controlled size (0.5mm to 2.0mm diameter) and coated with modified release composition, ensuring uniform drug distribution and maintaining inter-pellet homogeneity while providing prolonged release over 12-24 hours

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent controls the particle size parameter of the inert nucleus within specific ranges (0.5mm to 2.0mm diameter) and maintains size uniformity (standard deviation not exceeding 0.5mm). This parameter control ensures consistent coating thickness and drug distribution across all pellets, resolving the homogeneity issue while maintaining extended release duration

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If modified release composition is applied to provide sustained release, then duration of action is improved, but dosification uniformity deteriorates

Engineering Contradiction:

Improvesustained release durationVSAvoiddosification uniformity

Core Design Contradiction:

Duration of action of moving objectVSMeasurement precision

Solution Approach 1:

The patent applies coating to inert nuclei before final pellet formation, ensuring uniform drug distribution is established early in the process. The modified release coating is applied to each individual pellet surface, guaranteeing consistent dosing across all pellets while enabling sustained release kinetics

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses an inert nucleus (such as sugar spheres or gelatin beads) as an intermediary carrier for the active ingredient. This intermediary allows precise control of drug distribution within each pellet and facilitates uniform dosing while the coating composition provides the modified release mechanism for extended duration

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If multiple unit dosage form is used to improve dissolution profile, then therapeutic efficacy is improved, but production complexity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidproduction process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a self-service approach where the coating process automatically forms uniform pellets on inert nuclei without requiring complex post-processing steps. The pellets self-assemble with consistent morphology and drug distribution through the coating process itself, simplifying production while ensuring reliable therapeutic efficacy

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent uses a universal inert nucleus that serves multiple functions: as a carrier for the active ingredient, as a template for pellet formation, and as a core for coating application. This multi-functional approach simplifies the overall production process while maintaining high therapeutic efficacy through consistent pellet formation

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP4125825B1A modified release multiple unit oral dosage form of doxylamine succinate and pyridoxine hydrochloride and a process for its preparation

Publication Date: 2024.01.31 ITALFARMACO SPA

AI summary

A modified release multiple unit oral dosage form of doxylamine succinate and pyridoxine hydrochloride and a process for its preparation The present invention relates to modified release multiple unit oral dosage form comprising: a first plurality of modified release pellets of doxylamine comprising: a pharmaceutically acceptable inert nucleus; an inner active coating layer comprising a doxylamine; optionally an intermediate enteric release coating layer; and an external modified release coating layer; and a second plurality of modified release pellets of pyridoxine or a pharmaceutically acceptable salt thereof comprising: a pharmaceutically acceptable inert nucleus; an inner active coating layer comprising pyridoxine or a pharmaceutically acceptable salt thereof; and an external modified release coating layer; wherein the particle size of the pharmaceutically acceptable inert nucleus of the first and the second plurality of pellets is such that at least 90% of the inert nuclei have a particle size from 300 µm to 1700 µm and a particle size variability of not more than200 µm measured by analytical sieving. It also relates to a process for its preparation and its use in therapy.