Robust Pellet Formulation for Enhanced Drug Absorption

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Solution Overview

Problem

Formulating pharmaceuticals with high drug absorption and solubility in the GI tract is challenging due to the brittleness, stickiness, or lightness of pellets caused by high concentrations of absorption and solubility enhancers, which complicates downstream processing and delivery, especially for acid-sensitive drugs and modified release formulations.

Innovation Solution

Combining a high dosage of an active drug agent with a surfactant-type absorption enhancer and a solubilizing agent that acts as a solvent, resulting in robust pellets that can withstand processing and maintain integrity, using specific examples like Amoxicillin with Labrasol and N-Methyl pyrrolidine.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high concentrations of absorption and solubility enhancers are used to improve drug absorption and solubility in the GI tract, then the absorption and solubility of the active drug agent is improved, but the pellets become brittle, sticky, or light, compromising their physical integrity and downstream processing capability

Engineering Contradiction:
Improveabsorption and solubility of active drug agentVSAvoidphysical integrity of pellets
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent changes the physical and chemical parameters of the enhancer components by selecting specific surfactants and solvents with optimized properties. It adjusts the concentration ranges of these components and their molecular characteristics to achieve the desired balance between enhancing drug absorption/solubility and maintaining pellet mechanical strength. This parameter optimization resolves the contradiction by finding the optimal point where both absorption enhancement and pellet integrity are satisfied.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite pellet formulations by combining multiple components: active drug agent, surfactant-type absorption enhancer, solubilizing agent, and additional excipients. This composite approach allows the different materials to work synergistically, where the surfactant and solubilizing agent components collectively provide both absorption enhancement and structural support, preventing pellet brittleness while maintaining high drug absorption potential.

Inventive Principle:
Principle #40Composite materials

2Reliability

If high concentrations of absorption and solubility enhancers are used to improve drug absorption, then the absorption enhancement is improved, but the pellets become too brittle or sticky, making downstream processing difficult

Engineering Contradiction:
Improveabsorption enhancementVSAvoiddownstream processing capability
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent optimizes processing parameters including drying conditions, compression forces, and temperature controls during pellet formation. By adjusting these parameters, the formulation maintains the beneficial absorption-enhancing properties while producing pellets with appropriate mechanical properties for downstream processing. The parameter optimization ensures that the pellets remain robust enough to withstand processing operations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces intermediary excipient components that act as bridges between the absorption-enhancing agents and the pellet matrix. These intermediary substances facilitate the integration of surfactants and solubilizing agents into the pellet structure without causing excessive brittleness or stickiness, thereby enabling smooth downstream processing while maintaining absorption enhancement capabilities.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If gelatin capsule delivery systems are used to provide liquid absorption enhancers, then the absorption enhancer delivery is simplified, but the system cannot provide site-specific delivery or modified release patterns for acid-sensitive drugs

Engineering Contradiction:
Improveabsorption enhancer deliveryVSAvoidsite-specific delivery capability
Core Design Contradiction:
Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent segments the delivery system into individual robust pellets that can be independently coated and engineered for specific release characteristics. Each pellet can be designed with different coating compositions and thicknesses to achieve site-specific delivery or modified release patterns. This segmentation allows the absorption enhancer to be delivered in a controlled manner to specific regions of the GI tract, overcoming the limitations of whole-capsule delivery systems.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces dynamic release characteristics through pH-dependent or time-dependent coatings on the robust pellets. These dynamic features allow the pellet to respond to changing GI tract conditions, providing site-specific delivery or controlled release patterns. The coating system can be designed to dissolve at specific pH levels or over extended periods, enabling adapted delivery for acid-sensitive drugs while maintaining the simplicity of oral administration.

Inventive Principle:
Principle #15Dynamics

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 combination of surfactants and solvents creates pellets that are less brittle and non-sticky, enabling efficient downstream processing such as drying, coating, and compression, improving product yield and allowing for targeted GI tract delivery with enhanced absorption and solubility.

Implementation Method 1

a surfactant-type absorption enhancer

Methodology Applied
Scientific EffectSurfactant: Surfactant

Implementation Method 2

a solubilizing agent that acts as a solvent for the active drug component

Methodology Applied
Scientific EffectSolubility enhancement: Solvation

Data Source

PatentUS8758820B2Robust pellet
Publication Date: 2014.06.24 SHIONOGI INC

AI summary

Compositions and methods for making robust pellets that contain a high percentage, by weight, of active drug agent, and which also contain additional components that enhance the absorption and solubility of the active drug agent within the gastrointestinal tract (GI tract) without diminishing the robust nature of the pellet, are disclosed.