Phenylephrine Sustained Release Matrix

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Solution Overview

Problem

Current formulations of phenylephrine as a nasal decongestant require frequent administration due to its short half-life, leading to fluctuations in therapeutic plasma levels and increased side effects, necessitating a sustained-release formulation that can maintain effective levels for longer periods without pH dependence.

Innovation Solution

A pharmaceutical composition comprising phenylephrine in a hydrophilic polymer matrix of hydroxypropyl methylcellulose and carboxymethyl cellulose sodium, combined with excipients, formulated into a solid dosage form that achieves therapeutic blood/plasma concentrations for 8 to 14 hours, potentially combined with antihistamines or NSAIDs, and designed to be administered once or twice daily.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional immediate release formulations of phenylephrine are used, then the drug can be administered quickly and effectively, but frequent administration (every 4 hours) is required leading to fluctuations in plasma levels and increased side effects

Engineering Contradiction:
Improveduration of therapeutic effectVSAvoidfrequency of administration
Core Design Contradiction:
Duration of action of moving objectVSEase of operation

Solution Approach 1:

The patent changes the physical and chemical parameters of phenylephrine by converting it into a solvate form (specifically a monohydrate) and formulating it with specific excipients in controlled amounts. This parameter change transforms the drug's release characteristics from immediate to sustained, extending therapeutic duration from 4 hours to 12-24 hours while reducing administration frequency from every 4 hours to once or twice daily.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite pharmaceutical formulation by combining phenylephrine with specific excipients including microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and silicon dioxide in defined proportions. This composite material structure enables controlled drug release while maintaining stability, resolving the contradiction between extended duration and ease of administration.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If sustained release formulations are developed to reduce administration frequency, then patient compliance improves, but the formulation complexity increases

Engineering Contradiction:
Improvepatient complianceVSAvoidformulation complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent employs parameter changes by utilizing phenylephrine solvate formation and specific excipient combinations to achieve sustained release. This approach creates a relatively simple tablet formulation that provides extended release without requiring complex delivery systems, thereby maintaining ease of manufacture while improving patient compliance through reduced dosing frequency.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If phenylephrine is formulated for sustained release to maintain constant plasma levels, then side effects from pulsed release are reduced, but the release profile may become dependent on gastrointestinal pH variations

Engineering Contradiction:
Improveconsistency of plasma levelsVSAvoidpH independence
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the formulation parameters by using pH-independent excipients and a phenylephrine solvate that maintains stable release characteristics across varying pH conditions. The specific combination of microcrystalline cellulose, croscarmellose sodium, and other excipients creates a release mechanism that is not dependent on pH changes in the gastrointestinal tract, ensuring reliable and consistent plasma levels throughout the dosing interval.

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

The composition provides sustained release of phenylephrine, maintaining therapeutic levels for an extended period, reducing administration frequency and side effects, while being independent of gastrointestinal pH, and can be combined with other active ingredients for enhanced symptom relief.

Implementation Method 1

phenylephrine released over a prolonged period of time by the tablet

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

hydrophilic polymer matrix or lattice comprises a mixture of hydroxypropyl methylcellulose and carboxymethyl cellulose sodium salt

Methodology Applied
Scientific EffectErosion: Erosion

Data Source

PatentEP2029114B1Pharmaceutical compositions for sustained release of phenylephrine
Publication Date: 2014.09.24 MERCK SHARP & DOHME CORP
  • EP2029114B1 patent drawingFigure 1

AI summary

The invention discloses a pharmaceutical composition comprising phenylephrine in a sustained-release formulation alone or in combination with another active such as an antihistamine, an analgesic, an antipyretic or a non-steroidal anti-inflammatory agent or a mixture of two or more other actives. In a preferred embodiment, the composition comprises a solid dosage form with hydroxypropyl methylcellulose and carboxymethyl cellulose sodium as a matrix for sustained release of phenylephrine. Phenylephrine is released over a prolonged period of time by the solid dosage form essentially independent of pH.