Solid Dissolution Compositions for Biorelevant Media Preparation
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Solution Overview
Problem
Current methods for preparing biorelevant gastrointestinal media, such as FaSSIF and FeSSIF, are not cost-efficient, versatile, or suitable for routine laboratory use due to solvent removal issues and limited shelf-life, leading to heterogeneous micelles and potential residual solvent effects that affect solubility and dissolution profiling of poorly water-soluble compounds.
Innovation Solution
Development of solid dissolution compositions (SDC) comprising bile salts and phospholipids, which can be scaled up for commercial use, providing a robust and reproducible method to prepare biorelevant media over wide pH and osmolality ranges, simulating intestinal fluids in the fasted and fed states, and allowing for long-term storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If biorelevant gastrointestinal media are prepared using conventional methods with solvent removal, then the media can simulate intestinal fluids, but the method is not cost-efficient and has limited shelf-life due to micelle aggregation and lipid oxidation
Solution Approach 1:
The patent changes the physical state parameter of the bile salt and phospholipid mixture from liquid/solution to solid form through controlled drying processes. This parameter change enables the media to be prepared in advance, stored long-term, and reconstituted when needed, thereby improving productivity and cost-efficiency while maintaining biorelevance
Solution Approach 2:
The patent applies preliminary action by preparing the bile salt and phospholipid mixture in solid form in advance, before actual dissolution tests are needed. The solid mixture can be stored and then quickly reconstituted by adding water or buffer, eliminating the need for time-consuming solvent removal steps each time media are prepared
2Reliability
If biorelevant media are prepared freshly by removing chlorinated solvent from emulsions, then simulated intestinal fluids can be obtained, but the process is not expedient or versatile for routine laboratory use
Solution Approach 1:
The patent extracts the harmful chlorinated solvent from the system entirely by using alternative preparation methods that form solid bile salt-phospholipid mixtures without requiring chlorinated solvents. This eliminates the need for solvent removal steps and makes the procedure suitable for routine laboratory use
Solution Approach 2:
The patent creates a stable solid composition that can be stored long-term and used repeatedly, replacing the conventional approach that requires fresh preparation each time. This disposable-like convenience allows researchers to simply add the solid mixture to water or buffer when needed
3Productivity
If conventional dissolution media with SDS are used, then sink conditions are achieved for determining dissolution profiles, but the media are not physiologically relevant and may not forecast in vivo pharmacokinetic profiles reliably
Solution Approach 1:
The patent creates a composite material combining bile salts and phospholipids in specific ratios to form a solid mixture that, when reconstituted, provides both the sink conditions needed for dissolution testing and the physiological relevance of intestinal fluids. This composite approach achieves both testing capability and biological fidelity
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 SDCs enable the preparation of stable, biorelevant media that accurately simulate intestinal fluids, improving the assessment of poorly water-soluble active compounds' solubility and dissolution characteristics, facilitating in vitro-in vivo correlation and bioequivalence assessments, while offering convenience and cost-effectiveness for quality control and formulation development.
Implementation Method 1
biorelevant intestinal media comprising physiologically more relevant solubilisers such as lecithin, lysolecithin, bile salts, mono glycerides, fatty acids and mixed micelles thereof
Implementation Method 2
examine the solubility and dissolution characteristics of poorly water-soluble active compounds
Implementation Method 3
solid dissolution compositions (SDC) comprising essentially combinations of at least one bile salt and at least one phospholipid and a method for preparing large scale commercial quantities of particulate compositions by removing solvent from solutions
Data Source
AI summary
There are described solid compositions or examining drug solubility comprising bile salts and phospholipids, optionally containing buffer components suitable for preparation of intestinal media that simulate the composition of the intestinal fluids in fasted and fed states.