Antacid-Stabilized Proton Pump Inhibitor Formulations
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Solution Overview
Problem
Existing pharmaceutical formulations of acid-labile proton pump inhibitors face challenges in maintaining stability and bioavailability due to acid degradation in the stomach, particularly with enteric-coated systems that can be disrupted, leading to variable in-vivo performance and inter-subject variability.
Innovation Solution
The development of solid oral dosage forms containing an acid-labile proton pump inhibitor combined with a sufficient amount of antacid, such as sodium bicarbonate, to raise gastric pH and prevent degradation, along with optimized disintegrant and binder levels, ensuring timely and effective drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If enteric-coated formulations are used to protect acid-labile proton pump inhibitors from gastric acid degradation, then drug stability is improved, but in-vivo performance becomes variable and inter-subject variability increases due to pH-dependent dissolution and uncertain gastric retention time
Solution Approach 1:
An antacid intermediary substance is introduced to temporarily raise gastric pH and create a protective environment for the acid-labile proton pump inhibitor. The antacid acts as a mediator between the harsh acidic stomach environment and the sensitive drug, allowing immediate release without enteric coating while maintaining drug stability during the critical absorption window.
Solution Approach 2:
The formulation changes the pH parameter of the gastric environment by incorporating antacid substances. This temporary pH elevation prevents acid degradation of the proton pump inhibitor during its release and absorption phase, achieving both stability and reliable performance without requiring enteric coating.
2Speed
If immediate release formulations are used without enteric coating, then dissolution speed is improved, but drug degradation increases due to exposure to gastric acid
Solution Approach 1:
The antacid serves as a protective intermediary that creates a temporary favorable environment for immediate release. It allows the drug to dissolve rapidly while simultaneously protecting it from acid degradation through pH elevation, resolving the contradiction between speed and stability.
Solution Approach 2:
The antacid provides preliminary protection against acid degradation before the drug is fully released and absorbed. By raising gastric pH in advance, the formulation prevents the harmful acid-from attacking the drug during its vulnerable release phase, enabling stable immediate release.
3Stability of the object's composition
If high amounts of antacid (greater than 11 mEq) are used to ensure sufficient pH elevation, then drug stability is improved, but formulation complexity and dosage size increase
Solution Approach 1:
The formulation uses a moderate, optimized amount of antacid (about 5-11 mEq) that provides sufficient pH elevation for drug stability without the excessive amounts previously required. This partial action achieves the necessary protective effect while maintaining formulation simplicity and acceptable dosage size.
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
This approach enhances the bioavailability and stability of proton pump inhibitors, achieving a therapeutically effective concentration within 30 to 75 minutes, with bioequivalence to higher antacid formulations, and maintaining serum concentration for an extended period, effectively treating gastrointestinal disorders.
Implementation Method 1
at least one antacid sufficient to increase gastric pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid
Data Source
AI summary
The present invention relates to pharmaceutical formulations comprising at least one acid-labile proton pump inhibiting agent and at least one antacid, which have improved bioavailability, chemical stability, physical stability, dissolution profiles, disintegration times, safety, as well as other improved pharmacokinetic, pharmacodynamic, chemical and/or physical properties. The present invention is directed to methods, kits, combinations, and compositions for treating, preventing or reducing the risk of developing a gastrointestinal disorder or disease, or the symptoms associated with, or related to, a gastrointestinal disorder or disease in a subject in need thereof.