Lapatinib Particle Size and Surface Area for Dissolution
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Solution Overview
Problem
Poor aqueous solubility and in vivo dissolution rates limit the bioavailability of many drugs, necessitating methods to enhance drug absorption and bioavailability.
Innovation Solution
Development of lapatinib particles with a specific surface area of at least 10 m2/g and a mean particle size of 0.7 μm to 8 μm, produced using a method involving a solvent and compressed fluid under supercritical conditions, which are then used in compositions for treating tumors, including breast and pancreatic carcinomas, with optional administration of capecitabine and letrozole.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional drug formulations are used, then manufacturing is simple, but dissolution rate and bioavailability are poor
Solution Approach 1:
The patent applies parameter changes by controlling particle size (0.7-8 μm) and specific surface area (≥10 m²/g) of lapatinib particles to enhance dissolution rate. The supercritical fluid processing parameters (pressure, temperature, CO2 flow rate) are optimized to produce particles with these specific characteristics that improve bioavailability while managing manufacturing complexity.
Solution Approach 2:
The patent utilizes phase transitions of supercritical carbon dioxide to produce lapatinib particles. CO2 is transformed from supercritical phase to gaseous phase during depressurization, enabling solvent-free particle formation. This phase transition mechanism simplifies the process by eliminating the need for organic solvent removal while achieving the desired particle characteristics for improved dissolution.
2Productivity
If particle size is reduced to increase surface area, then dissolution rate improves, but manufacturing precision becomes more difficult
Solution Approach 1:
The patent replaces mechanical particle size reduction methods (grinding, milling) with a chemical/physical process using supercritical fluid precipitation. This substitution enables precise control of particle size (0.7-8 μm) and surface area (≥10 m²/g) through controlled phase transitions and supersaturation, achieving manufacturing precision that mechanical methods cannot provide while maintaining scalability.
Solution Approach 2:
The patent employs periodic action through controlled cycling of pressure and temperature during supercritical fluid processing. The cyclic compression and decompression of CO2, along with controlled solvent addition and removal, enable consistent production of particles within the target size range, managing the complexity of precise particle size control through repeatable process cycles.
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 increased specific surface area of lapatinib particles significantly enhances dissolution rates, improving drug bioavailability and reducing dosing frequency and side effects, particularly when administered directly to tumors.
Implementation Method 1
contacting the atomized droplets with the compressed fluid, to cause depletion of the solvent from the atomized droplets
Implementation Method 2
passing the solution out of a nozzle orifice and into the pressurizable chamber to produce an output stream of atomized droplets
Data Source
AI summary
The disclosure provides particles of at least 95% by weight of lapatinib, or a pharmaceutically acceptable salt thereof, wherein the particles have a specific surface area (SSA) of at least 10 m2/g and have a mean particle size by volume distribution of between about 0.7 μm and about 8 μm.