pH-Controlled Pulsatile Drug Delivery via Swellable Coating

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current pH-controlled drug delivery systems for the gastrointestinal tract face challenges in achieving rapid and site-specific drug release due to slow dissolution of pH-sensitive coatings at intestinal pH values slightly above the setpoint, leading to lag times and reduced drug delivery effectiveness at the target site.

Innovation Solution

Incorporating a swellable agent into the matrix of a pH-sensitive coating layer, where the agent is embedded below the percolation threshold, allowing for rapid absorption of aqueous fluid and complete disintegration of the coating upon pH change, resulting in a pulsatile release of the drug.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a pH-sensitive coating layer is used to control drug release at intestinal pH, then site-specific delivery is achieved, but the dissolution rate is slow when pH is only slightly above the setpoint

Engineering Contradiction:

Improvesite-specific deliveryVSAvoiddissolution rate

Core Design Contradiction:

ReliabilityVSSpeed

Solution Approach 1:

The patent combines pH-sensitive polymer material with swellable particles to create a composite coating layer. The pH-sensitive polymer provides pH-responsive behavior for site-specific delivery, while the swellable particles embedded within the matrix provide rapid swelling and disintegration capability when exposed to intestinal fluid, thereby accelerating drug release without compromising targeting reliability

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The coating layer is designed with a porous structure formed by embedding swellable particles within the pH-sensitive polymer matrix. This porous architecture allows intestinal fluid to penetrate rapidly and reach the drug core, facilitating faster dissolution and release while maintaining the pH-triggered release mechanism

Inventive Principle:

Principle #31Porous materials

2Reliability

If conventional pH-sensitive coatings are used, then drug protection in stomach is achieved, but lag time occurs before drug release at target site

Engineering Contradiction:

Improvedrug protectionVSAvoidlag time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The swellable particles are pre-embedded within the pH-sensitive polymer matrix during coating formulation. When the coating encounters intestinal fluid, the pH-sensitive polymer rapidly dissolves and the pre-positioned swellable particles immediately absorb fluid and swell, creating a push effect that quickly propels the coating apart and releases the drug, thereby eliminating lag time while maintaining protective function

Inventive Principle:

Principle #10Preliminary action

3Speed

If the concentration of swellable agent is increased to accelerate coating disintegration, then drug release rate improves, but structural integrity is compromised

Engineering Contradiction:

Improvedrug release rateVSAvoidcoating structural integrity

Core Design Contradiction:

SpeedVSStability of the object's composition

Solution Approach 1:

The patent optimizes the concentration of swellable particles within the pH-sensitive polymer matrix, finding the critical threshold where sufficient swelling pressure is generated to disintegrate the coating rapidly, while the polymer matrix maintains enough structural integrity to provide protection during gastric transit. This parameter optimization balances release speed with protective function

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

This approach significantly enhances the rate of drug release, ensuring a high concentration of the drug is delivered rapidly and effectively at the desired intestinal site, overcoming limitations of slow release and lag times in conventional systems.

Implementation Method 1

the swellable agent is embedded in a continuous matrix of the pH sensitive coating polymer... the swellable agent, which swells enough to accelerate the further and complete disintegration of the coating

Methodology Applied

Scientific EffectSwelling: Hydrogel

Implementation Method 2

Enteric polymeric materials are primarily weak acids containing acidic functional groups, which are capable of ionization at elevated pH. As the pH increases in the intestinal tract, these functional groups ionize, and the polymer becomes soluble in the intestinal fluids.

Methodology Applied

Scientific EffectpH-dependent dissolution: Erosion

Data Source

PatentUS11744803B2PH-controlled pulsatile delivery system, methods for preparation and use thereof

Publication Date: 2023.09.05 STICHTING GRONINGEN CENT FOR DRUG RES

AI summary

The invention relates to delivery systems that allow for the pulsatile release of a substance, such as a drug, in response to a change in pH. More specifically, it relates to drug administration to the GI tract, in particular to site-specific intestinal drug delivery via the oral route. Provided is a pH-controlled pulsatile release system (PPRS) comprising a core surrounded by a coating layer, wherein said core comprises an active substance and wherein said coating layer comprises a pH-sensitive coating material wherein a swellable agent is embedded. Said swellable agent is capable of taking up at least 1.1 times, preferably at least 5 times, more preferably at least 10 times its weight in water. Also provided is a pharmaceutical composition comprising a PPRS, in particular a colon-specific PPRS.