Obeticholic Acid Particle Formulation for Solubility and Stability
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Solution Overview
Problem
Existing obeticholic acid compositions face challenges with poor dissolution, solubility, and stability, which hinder their effectiveness in treating conditions such as primary biliary cirrhosis, primary sclerosing cholangitis, and liver diseases.
Innovation Solution
Formulations of obeticholic acid in the form of particles with a diameter of 200 μm or less, combined with specific excipients like sodium starch glycolate and microcrystalline cellulose, enhance dissolution and stability, and are prepared through jet-milling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If obeticholic acid is formulated with conventional excipients and processing methods, then manufacturing is straightforward, but dissolution and solubility are poor
Solution Approach 1:
The patent applies parameter changes by reducing particle size to 200 μm or less through jet-milling, which fundamentally alters the physical state of obeticholic acid particles. This parameter change increases surface area and improves dissolution rate and solubility without complicating the manufacturing process, as jet-milling is a established technology.
Solution Approach 2:
The patent uses composite materials by combining obeticholic acid with specific excipients (sodium starch glycolate and microcrystalline cellulose) in a formulated composition. This composite approach enhances dissolution and stability properties while maintaining ease of manufacture through conventional tabletting processes.
2Reliability
If obeticholic acid is formulated to improve dissolution, then solubility increases, but stability deteriorates
Solution Approach 1:
The patent resolves this contradiction by creating a composite formulation where obeticholic acid is combined with stabilizing excipients (sodium starch glycolate and microcrystalline cellulose). This composite structure maintains improved solubility through particle size reduction while the excipients provide stability, preventing degradation of the active ingredient.
Solution Approach 2:
The patent applies local quality by creating a specific formulation environment around the obeticholic acid particles using excipients with particular properties. The sodium starch glycolate and microcrystalline cellulose provide localized protection and stability to the particle surfaces, allowing high solubility to be maintained without sacrificing stability.
3Reliability
If particle size is reduced to improve dissolution, then dissolution rate increases, but manufacturing complexity increases
Solution Approach 1:
The patent changes the particle size parameter to 200 μm or less using jet-milling, which improves dissolution rate. This parameter change does not significantly increase manufacturing complexity because jet-milling is a conventional technology and the patent provides specific guidance on formulation components and processing parameters to maintain ease of manufacture.
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 formulations improve solubility and stability, enabling effective treatment of liver diseases and cancers by ensuring consistent drug delivery and bioavailability.
Implementation Method 1
Formulations of obeticholic acid in the form of particles with a diameter of 200 μm or less, combined with specific excipients like sodium starch glycolate and microcrystalline cellulose, enhance dissolution and stability, and are prepared through jet-milling.
Data Source
AI summary
The disclosure relates to obeticholic acid formulations with improved stability, dissolution, and/or solubility, methods of preparing the same for use and methods of treating various diseases and conditions.