Press-Coated Tablet Delayed Release via Swellable Polymer Layer

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Solution Overview

Problem

Existing drug release formulations for conditions like hypertension and cardiovascular diseases often rely on complex structures that are costly to manufacture and can malfunction, leading to inappropriate drug administration, and lack a simple method for delayed and prolonged release according to circadian rhythms.

Innovation Solution

A press-coated tablet formulation using a delayed release layer of wax and low-substituted hydroxypropyl cellulose (L-HPC) surrounding a core with a wax and active agent, which delays drug release for 3-6 hours before providing continuous release over 2-8 hours, tailored for administration before sleep to address morning cardiovascular needs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If complex release structures are used to achieve delayed and prolonged drug release, then the drug release profile can be controlled according to circadian rhythms, but the manufacturing cost increases and the risk of malfunction increases

Engineering Contradiction:
Improvedrug release controlVSAvoidformulation structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The formulation is segmented into distinct functional layers: an immediate release layer containing the active ingredient for rapid dissolution, and a delayed release layer containing swellable polymer granules that form a matrix for controlled release. This segmentation allows each layer to perform its specific function independently, achieving complex release profiles through simple layering rather than complex internal structures.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The delayed release layer is pressed onto the immediate release core, creating a nested structure where the core is embedded within the coating layer. This nested arrangement allows the formulation to achieve delayed and prolonged release functionality without requiring complex internal mechanisms, as the outer layer naturally controls the release timing while the inner core provides immediate availability.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Manufacturing precision

If precision drilled holes are formed in the outer membrane to achieve delayed release, then the drug release timing can be controlled, but the manufacturing complexity and cost increase

Engineering Contradiction:
Improverelease timing controlVSAvoidformulation fabrication
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The invention replaces mechanical drilling operations with a press-coating process where the delayed release layer is applied under pressure. The swellable polymer granules in the coating layer naturally create release channels through swelling in gastric fluids, eliminating the need for precision drilling while achieving comparable or superior release control through a simpler, more scalable manufacturing process.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Duration of action of moving object

If complex multi-layer structures are used to achieve delayed prolonged release, then the drug release profile can be optimized, but the manufacturing cost increases

Engineering Contradiction:
Improvedrug release durationVSAvoidformulation production
Core Design Contradiction:
Duration of action of moving objectVSEase of manufacture

Solution Approach 1:

The delayed release layer serves multiple functions simultaneously: it provides the delayed release mechanism through swellable polymer granules, creates a matrix for prolonged release, and acts as a protective coating for the immediate release core. This multi-functionality allows the formulation to achieve complex release profiles (delayed + prolonged release) using a single, simple press-coating operation rather than multiple sequential manufacturing steps.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 formulation ensures a therapeutic level of the active agent is maintained during critical morning hours when cardiovascular complications often occur, improving treatment efficacy while simplifying manufacturing and reducing complexity.

Implementation Method 1

a delayed release layer surrounding a core comprising the active agent, wherein the delayed release layer comprises a wax and the low-substituted hydroxypropyl cellulose (L-HPC): LH-32

Methodology Applied
Scientific EffectSwelling:

Implementation Method 2

the delayed release layer substantially delays release of the active agent within the core for between 3 - 6 hours after administration of the tablet by a subject

Methodology Applied
Scientific EffectControlled release:

Implementation Method 3

a core in which the active agent is admixed with a wax such as beeswax, carnuba wax, microcrystalline wax, hydrogenated castor oil

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 4

thereafter a prolonged release of the active agent from the core occurs, such that the active agent in the core is continuously released over a period of up to 2 - 8 hours

Methodology Applied
Scientific EffectDissolution:

Data Source

PatentEP2542226B1Delayed prolonged drug delivery
Publication Date: 2017.11.22 UNIV OF STRATHCLYDE
  • EP2542226B1 patent drawingFigure 1
  • EP2542226B1 patent drawingFigure 2
  • EP2542226B1 patent drawingFigure 3

AI summary

In one aspect, the present invention is concerned with a treatment where it is desired that an active agent is designed to be released in a prolonged manner at a time point some time after administration of the active agent. The present invention is particularly suited to administering an agent which may be released whilst a subject is sleeping, shortly before waking and continues to administer the drug during the early waking hours. As well as treating certain conditions by a particular regime, the invention also provides novel formulations for a delayed, followed by a prolonged release of drug.