Hot Melt Extrusion Solid Dispersion for Low Solubility Drugs
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Solution Overview
Problem
Compounds with low aqueous and oil solubility, such as NK-1 receptor antagonists, face bioavailability issues due to insolubility and adverse interactions with food, leading to reduced effectiveness and potential adverse reactions when taken orally.
Innovation Solution
The development of galenic compositions for oral administration using hot melt extrusion of active pharmaceutical ingredients with a poloxamer, specifically a water-soluble poloxamer like Lutrol F68, to create a hot melt extrudate that enhances solubility and bioavailability, overcoming insolubility in simulated intestinal fluid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compounds with low aqueous and oil solubility are administered orally, then the drug can be delivered to patients, but the bioavailability is insufficient due to insolubility
Solution Approach 1:
The patent changes the physical state of the drug from crystalline to amorphous form through hot melt extrusion processing. This parameter change in molecular arrangement and physical state dramatically increases aqueous solubility and bioavailability without altering the chemical structure of the NK-1 receptor antagonist
Solution Approach 2:
The patent creates a composite material system by combining the NK-1 receptor antagonist with a hydrophilic carrier polymer (such as polyethylene glycol or poloxamer) through hot melt extrusion. This composite approach enhances the solubility of the hydrophobic drug while maintaining its pharmacological activity
2Reliability
If drugs are taken with food, then absorption may be enhanced, but adverse interactions occur that diminish drug effectiveness
Solution Approach 1:
The patent applies preliminary action by pre-formulating the drug in an optimized delivery system (hot melt extrudate with hydrophilic carrier) before administration. This pre-processing of the drug substance ensures rapid dissolution and absorption independent of food presence, preventing food-drug interactions from occurring
3Reliability
If vitamin and herbal supplements are taken with prescribed medication, then comprehensive treatment is provided, but adverse reactions occur
Solution Approach 1:
The patent uses preliminary action by optimizing the drug's physical formulation beforehand through hot melt extrusion. This creates a highly soluble, rapidly dissolving dosage form that achieves therapeutic效果 quickly and predictably, reducing the window for potential interactions with supplements and minimizing adverse reactions
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 approach enables sufficient availability of the active compound at the site of action, improving oral bioavailability and reducing adverse interactions by forming a microcrystalline solid dispersion with improved dissolution characteristics.
Implementation Method 1
the compositions and process employ a hot melt extrusion of the active pharmaceutical ingredient and a poloxamer
Implementation Method 2
forming a microcrystalline solid dispersion with improved dissolution characteristics
Implementation Method 3
a water-soluble poloxamer like Lutrol F68, to create a hot melt extrudate that enhances solubility and bioavailability
Data Source
AI summary
The invention relates to a process for preparing a pharmaceutical tablet composition which comprises an active pharmaceutical ingredient of formula Iwherein the definitions are described in claim 1, or pharmaceutically acceptable acid addition salts thereof and a water soluble poloxamer in which the compound of formula I and the water soluble poloxamer are processed by hot melt extrusion, and then the hot melt extrudate is mixed with other ingredients to form a tablet, that is optionally coated with a composition comprising an immediate release film coating system and purified water. The invention also relates to such pharmaceutical compositions and hot melt extrudates.