Enteric Coating for Acid-Labile Drugs Using Citrate Plasticizers
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Solution Overview
Problem
Existing pharmaceutical compositions for acid-labile active pharmaceutical ingredients, such as pancreatin, face challenges due to incompatibility with acidic stomach environments, and recent health guidelines restrict the use of monomeric phthalic acid ester plasticizers and synthetic oils, necessitating a new enteric-coated oral dosage form that avoids these excipients while ensuring targeted release and stability.
Innovation Solution
An enteric-coated oral dosage form for acid-labile drugs, specifically pancreatin, using a coating comprising a mixture of cetyl alcohol and triethyl citrate as plasticizers, along with film-forming agents and optional anti-sticking agents, which is substantially free of monomeric phthalic acid ester plasticizers and synthetic oils, ensuring controlled release in the upper intestine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monomeric phthalic acid ester plasticizers and synthetic oils are used in enteric-coated oral dosage forms, then the coating flexibility and release properties are improved, but the formulation becomes incompatible with current health guidelines and regulatory requirements
Solution Approach 1:
The patent removes monomeric phthalic acid ester plasticizers and synthetic oils from the enteric coating formulation, extracting the problematic components while retaining the essential functionality through alternative plasticizers and lubricants that comply with health guidelines
Solution Approach 2:
The patent employs composite material strategies by combining multiple alternative plasticizers (e.g., citrate esters, adipate esters) and lubricants in specific ratios to achieve the desired coating properties without using restricted substances, creating a composite formulation that meets both performance and regulatory requirements
2Reliability
If an enteric coating is applied to protect acid-labile drugs, then gastric acid resistance is improved, but the complexity of the formulation increases
Solution Approach 1:
The enteric coating serves multiple functions simultaneously: it provides gastric acid resistance, ensures targeted release in the upper intestine, and acts as a barrier to protect the acid-labile drug from degradation, thereby achieving multiple objectives with a single formulation approach
Solution Approach 2:
The patent optimizes the coating formulation by adjusting parameters such as plasticizer type and concentration, film-forming agent composition, and coating thickness to achieve the desired balance between gastric acid resistance and controlled release properties
3Manufacturing precision
If controlled release is achieved through enteric coating, then targeted delivery to the upper intestine is improved, but the manufacturing process becomes more complex
Solution Approach 1:
The enteric coating is applied in advance to the oral dosage form core, pre-establishing the controlled release properties and gastric acid resistance before final product assembly, thereby simplifying the overall manufacturing process while ensuring precise targeted delivery
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 formulation provides effective targeted release and storage stability for pancreatin, maintaining gastric acid resistance and preserving lipase content, while adhering to current health guidelines by avoiding restricted excipients, thus addressing the incompatibility issues and regulatory concerns.
Implementation Method 1
the enteric coating as disclosed herein is substantially free of both, monomeric phthalic acid ester plasticizers, such as dibutyl phthalate, and synthetic oils, such as paraffins or mineral oils, while at the same time providing the desired targeted release and storage stability
Implementation Method 2
providing an enteric-coated oral dosage form of an acid-labile drug wherein the enteric-coating comprises at least one plasticizer and at least one film-forming agent
Data Source
AI summary
An enteric-coated oral dosage form comprising an acid labile active pharmaceutical ingredient where the composition is substantially free of monomeric phthalic acid esters and synthetic oils is described herein. Also provided are methods for making and using the enteric-coated oral dosage form. The disclosed pharmaceutical compositions comprise an enteric coating which includes at least one plasticizer, at least one film-forming agent and optionally at least one anti-sticking agent.