Disulfide-Linked Proton Pump Inhibitor Formulations
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Solution Overview
Problem
Pharmaceutically active compounds containing sulfur groups, such as proton pump inhibitors, are typically unstable and pose formulation difficulties due to their acid lability, leading to low bioavailability and the need for costly enteric coatings to protect against stomach acidity.
Innovation Solution
Formation of disulfide compounds between pharmaceutically active compounds with sulfhydryl, sulfinyl, or sulfonamide groups and pharmacologically acceptable sulfhydryl compounds, either in vitro or in vivo, without the use of acids, to create stable formulations that do not require enteric coatings.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pharmaceutically active compounds containing sulfur groups are used, then biological activity is achieved, but stability in acidic environments deteriorates
Solution Approach 1:
The patent uses sulfhydryl compounds as intermediaries to form disulfide bonds with the sulfur groups of pharmaceutically active compounds. This intermediary mechanism protects the acid-labile PACs from direct exposure to gastric acid, thereby improving stability while maintaining biological activity.
Solution Approach 2:
The invention creates composite formulations by combining pharmaceutically active compounds with sulfhydryl compounds to form disulfide-linked complexes. This composite structure provides enhanced acid stability compared to the individual components, allowing the formulation to withstand gastric conditions without requiring enteric coating.
2Reliability
If enteric coatings are applied to protect PACs from stomach acidity, then stability is improved, but device complexity and cost increase
Solution Approach 1:
The patent removes the need for enteric coating by extracting the protection function and transferring it to the chemical structure itself through disulfide bond formation. The intrinsic chemical stability provided by the disulfide linkage eliminates the requirement for additional protective formulation layers, simplifying the overall formulation.
3Ease of manufacture
If conventional PAC formulations are used, then ease of manufacture is maintained, but bioavailability deteriorates due to instability
Solution Approach 1:
The invention changes the chemical parameters of the formulation by introducing sulfhydryl compounds that react to form disulfide bonds. This parameter change transforms the chemical stability profile of the formulation, improving bioavailability while maintaining ease of manufacture through straightforward mixing and reaction processes.
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 resulting disulfide compounds exhibit enhanced stability in acidic environments, improved bioavailability, and effective gastric acid inhibition, making them suitable for treating gastrointestinal disorders without the need for enteric coatings.
Implementation Method 1
a sulfhydryl group of a pharmacologically acceptable sulfhydryl compound in an oxidised form SB
Implementation Method 2
PAC-SA is a residue of a pharmaceutically active drug metabolite thereof or a pharmaceutically acceptable salt thereof containing a covalently bonded sulfur atom SA in the form of a reduced sulfhydryl, sulfinyl, sulfonyl or sulfonamide group
Data Source
AI summary
Disclosed herein is a method for the production of disulfide compounds of the formula IPAC-SA—SB—R* (I)wherein PAC-SA is a residue of a pharmaceutically active drug a metabolite thereof or a pharmaceutically acceptable salt thereof that is covalently bonded via the sulfur atom, SA of a reduced sulfhydryl, sulfinyl, sulfonyl or sulfonamide group to the sulfur atom SB of an oxidized sulfhydryl group of a pharmacologically acceptable sulfhydryl compound in the absence of an acid. Preferably the pharmaceutically active drug is a proton pump inhibitor and the sulfhydryl compound is N-acetyl cysteine. The disulfide compounds according to the invention can be prepared either in vitro or in vivo and are stable in the acidic conditions of the stomach. Pharmaceutical compositions containing compounds of the formula I and a method for the treatment or prophylaxis of gastrointestinal disorders using compounds of the formula I are also described.