Ticagrelor Solid Dispersion With Surfactant-Enhanced Dissolution
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Solution Overview
Problem
Ticagrelor tablets exhibit low bioavailability due to low solubility and permeability, leading to limited dissolution improvement in existing solid dispersions.
Innovation Solution
A solid dispersion of ticagrelor comprising a pharmaceutically acceptable high-molecular-weight polymer, a polyoxyethylene-based non-ionic surfactant, and optional additives like antioxidants, fillers, and lubricants, prepared through methods such as fluidized bed granulation, to enhance dissolution and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If ticagrelor is formulated as conventional tablets, then manufacturing is simple, but bioavailability is low due to low solubility and permeability
Solution Approach 1:
The patent changes the physical state of ticagrelor from crystalline to amorphous form through solid dispersion technology, fundamentally altering its dissolution properties. This phase transition enables the drug to achieve high solubility while maintaining manufacturability through established solid dispersion processes
Solution Approach 2:
The patent creates a composite system by dispersing ticagrelor molecules within a polymer matrix (such as HPMC or Eudragit), forming a solid dispersion that combines the properties of both the drug and polymer. This composite structure provides enhanced solubility, controlled release, and improved bioavailability while remaining manufacturable
2Reliability
If solid dispersion is used to improve dissolution, then bioavailability increases, but manufacturing complexity increases
Solution Approach 1:
The patent employs self-assembling properties of amphiphilic block copolymers that automatically form micellar structures around ticagrelor molecules during the formulation process. This self-organization reduces the need for complex processing steps and equipment, simplifying manufacturing while achieving enhanced dissolution
Solution Approach 2:
The patent uses surfactants and block copolymers as intermediary substances that mediate between the hydrophobic ticagrelor and the aqueous environment. These intermediaries form micelles and solubilization complexes that enhance drug dissolution without requiring complex formulation procedures
3Quantity of substance
If high specification tablets are used, then dosage strength is high, but dissolution rate remains low
Solution Approach 1:
The patent segments the high-dose ticagrelor into molecular-level dispersions within the polymer matrix, creating numerous small drug-polymer interaction sites. This segmentation increases the total surface area available for dissolution, enabling high-dose formulations to dissolve rapidly
Solution Approach 2:
The patent changes the aggregation state of ticagrelor from large crystalline structures to molecularly dispersed amorphous states within the polymer matrix. This parameter change dramatically increases the dissolution surface area and rate, allowing high-dose formulations to achieve rapid dissolution
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 solid dispersion significantly increases ticagrelor's dissolution and bioavailability, with formulations showing up to four times the dissolution rate compared to ticagrelor tablets, improving its pharmacokinetic profile.
Implementation Method 1
a surfactant comprising a polyoxyethylene-based non-ionic surfactant
Implementation Method 2
The solid dispersion significantly increases ticagrelor's dissolution and bioavailability, with formulations showing up to four times the dissolution rate compared to ticagrelor tablets
Data Source
AI summary
A ticagrelor solid dispersion, a method for preparing same, and use thereof. The ticagrelor solid dispersion includes the following components: (a) an active ingredient, comprising ticagrelor and/or a pharmaceutically acceptable salt thereof; (b) a carrier, including a pharmaceutically acceptable high-molecular-weight polymer; and (c) a surfactant, including a polyoxyethylene non-ionic surfactant. The ticagrelor solid dispersion has significantly improved dissolution and improved bioavailability.