Orally Disintegrating PPI Pellets with Composite Enteric Coating
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current orally disintegrating compositions containing proton pump inhibitors (PPIs) are susceptible to alcohol-induced dose dumping, which can lead to fluctuations in drug concentration and pose safety concerns, and there is a need for formulations that maintain therapeutic efficacy even in the presence of alcohol.
Innovation Solution
Development of an orally disintegrating composition comprising enteric coated active cores with a disintegrant, which rapidly disintegrates in the oral cavity and maintains resistance to alcohol-induced dose dumping, ensuring a release profile similar to conventional compositions both with and without alcohol.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enteric coating materials (cellulose, vinyl, acrylic derivatives) are used to protect PPIs from stomach acid, then the PPIs are protected from degradation, but the coating becomes susceptible to alcohol-induced dose dumping
Solution Approach 1:
The patent uses a composite enteric coating system comprising multiple layers with different polymer materials. The inner layer contains cellulose acetate phthalate (CAP) and the outer layer contains hydroxypropyl methylcellulose phthalate (HPMCP). This composite structure provides synergistic protection where CAP provides initial acid resistance and HPMCP provides enhanced alcohol resistance, preventing dose dumping while maintaining PPI protection.
Solution Approach 2:
The patent modifies the chemical composition parameters of the enteric coating by selecting specific phthalate esters with appropriate molecular weights and substituting hydroxypropyl groups. These parameter changes enhance the coating's resistance to alcohol while maintaining its pH-dependent solubility characteristics, thereby preventing dose dumping in the presence of alcohol.
2Reliability
If conventional enteric coated tablets are used, then PPIs are protected during stomach passage, but patient compliance is reduced due to swallowing difficulties
Solution Approach 1:
The patent divides the enteric coated tablet into smaller granules or pellets, each individually coated with the enteric coating system. This segmentation allows the medication to be administered in a form that is easier to swallow while maintaining the protective function of the enteric coating. The segmented structure also improves disintegration characteristics in the oral cavity.
Solution Approach 2:
The patent applies the enteric coating selectively to specific regions or surfaces of the dosage form components. The coating is applied to provide localized protection where needed while maintaining other desirable properties such as disintegration and dissolution in specific locations within the gastrointestinal tract.
3Ease of operation
If the enteric coating is designed for rapid disintegration in oral cavity, then patient compliance improves, but the coating may lose gastro-resistance and cause dose dumping
Solution Approach 1:
The patent designs the enteric coating with dynamic properties that allow it to respond differently to various environmental conditions. The coating maintains its integrity and resistance in acidic and alcoholic environments but undergoes controlled disintegration in neutral pH conditions of the oral cavity and intestinal fluids, providing both compliance improvement and dose dumping prevention.
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 composition effectively prevents alcohol-induced dose dumping, maintaining therapeutic equivalence to non-orally disintegrating forms, with less than 20% drug release in 15 minutes at 0.1N HCl and 40% ethanol, ensuring consistent drug absorption and safety.
Implementation Method 1
Enteric coating materials are polymers which contain acidic functional groups capable of being ionized at elevated pH values. At low pH values (e.g. the acidic environment of the stomach), the enteric polymers are not ionized, and therefore, insoluble.
Implementation Method 2
As the pH increases (e.g. when entering the small intestine), the acidic functional groups ionize and the polymer becomes soluble.
Implementation Method 3
an orally disintegrating composition comprising a therapeutically effective amount of a proton pump inhibitor and at least one disintegrant, wherein after administration, the composition substantially disintegrates in the oral cavity of a subject in need thereof within less than about 60 seconds
Data Source
AI summary
An orally disintegrating dosage form of a proton pump inhibitor, methods for its production and use thereof are provided. The dosage form includes a plurality of pellets containing a proton pump inhibitor admixed with a disintegrant to afford rapid disintegration in the oral cavity after administration.