Sodium Chenodeoxycholate Solid Forms for Colon Release Control
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Solution Overview
Problem
Existing formulations of chenodeoxycholic acid (CDCA) and its salts, such as sodium chenodeoxycholate (NaCDC), suffer from side effects like abdominal pain and cramping due to high local concentrations in the intestinal tract, and there are challenges in achieving controlled release due to varying water content along the colon, necessitating improved formulations for gastrointestinal disorders like IBS-C.
Innovation Solution
Development of solid forms of sodium chenodeoxycholate (NaCDC) with specific crystalline structures, including polymorphs and solvates, characterized by XRPD and DSC patterns, to enhance stability, solubility, and bioavailability, and the creation of bilayer tablets for controlled release in the colon.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a CDCA salt formulation is used to treat IBS-C, then therapeutic efficacy is improved, but abdominal pain and cramping side effects increase due to high local concentrations
Solution Approach 1:
The patent divides the single-dose formulation into multiple smaller doses administered throughout the day. This segmentation reduces the local concentration of CDCA salt in the intestine at any given time, thereby minimizing abdominal pain and cramping while maintaining overall therapeutic efficacy through cumulative dosing.
Solution Approach 2:
The patent modifies the local properties of the formulation by using specific salts (sodium or potassium chenodeoxycholate) and controlling their dissolution characteristics. This allows for more gradual release and distribution of the active ingredient in the intestinal tract, reducing peak local concentrations that cause side effects while preserving therapeutic action.
2Object-affected harmful factors
If controlled release formulation is implemented to reduce side effects, then local concentration is reduced, but release control becomes challenging due to decreasing water content along the colon
Solution Approach 1:
The patent exploits the natural gradient of water content along the gastrointestinal tract as a driving force for controlled release. By selecting appropriate salt forms and formulations that respond to varying water availability, the system achieves progressive release of CDCA from the stomach through the colon without requiring complex mechanical release mechanisms.
Solution Approach 2:
The formulation utilizes the body's own physiological environment—specifically the natural water content gradient in the GI tract—to drive the controlled release process. The formulation self-regulates its release rate based on local water availability, eliminating the need for external control mechanisms.
3Speed
If immediate release formulation is used, then therapeutic action is rapid, but side effects occur due to high peak concentrations
Solution Approach 1:
The patent replaces single immediate-release dosing with multiple smaller doses administered throughout the day. This maintains rapid therapeutic action at each dosing interval while preventing the accumulation of high peak concentrations that cause side effects.
Solution Approach 2:
The patent implements periodic dosing schedules (multiple times daily) to maintain therapeutic levels through cumulative effect rather than relying on high peak concentrations from single immediate-release doses. This periodic administration pattern sustains therapeutic action while minimizing side effects.
Data Source
AI summary
The present disclosure provides solid forms of sodium chenodeoxycholate (NaCDC), as well as compositions thereof and methods of using and preparing the same.