Enteric-Coated Pancreatin Formulation for Acid Resistance
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Solution Overview
Problem
Existing pharmaceutical compositions containing acid-labile active ingredients like pancreatin face incompatibility with the acidic environment of the stomach, necessitating a formulation that protects these drugs until they reach a more compatible pH in the GI tract, while also avoiding the use of restricted excipients such as monomeric phthalic acid ester plasticizers and synthetic oils.
Innovation Solution
An enteric-coated oral dosage form is developed, comprising film-forming agents, plasticizers (like cetyl alcohol and triethyl citrate) in amounts greater than 1.5% by weight, and optionally an anti-sticking agent, which provides controlled release and storage stability without using monomeric phthalic acid esters or synthetic oils, ensuring targeted delivery to the upper intestine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enteric coating is applied to protect acid-labile pancreatin from gastric acid, then gastric acid resistance is improved, but the formulation complexity increases due to additional coating components
Solution Approach 1:
The patent changes the chemical parameters of the enteric coating by using carboxymethyl cellulose phthalate with specific substitution degrees (25-85%) and controlling plasticizer content (1.5-20% w/w), thereby achieving optimized gastric acid resistance while managing formulation complexity through precise parameter specification
Solution Approach 2:
The patent creates a composite enteric coating system combining carboxymethyl cellulose phthalate with plasticizers (such as triethyl citrate, dibutyl sebacate, or cetyl alcohol) and optionally titanium dioxide, forming a composite material that provides both protective function and controlled flexibility while addressing the complexity through defined compositional ranges
2Stability of the object's composition
If conventional plasticizers like dibutyl phthalate are used in enteric coating, then coating flexibility and stability are improved, but health safety deteriorates due to regulatory restrictions on phthalic acid esters
Solution Approach 1:
The patent extracts and eliminates dibutyl phthalate and other monomeric phthalic acid esters from the enteric coating formulation, removing the harmful component while maintaining coating functionality through alternative plasticizers such as triethyl citrate, dibutyl sebacate, or cetyl alcohol
Solution Approach 2:
The patent introduces alternative plasticizers as intermediary substances that fulfill the same functional role as dibutyl phthalate (providing coating flexibility and stability) without the harmful health effects, such as using triethyl citrate or dibutyl sebacate as safe substitutes
3Reliability
If synthetic oils like mineral oil are used in pancreatin formulation, then drug delivery performance is improved, but health safety deteriorates due to regulatory advice against indiscriminate use
Solution Approach 1:
The patent removes synthetic oils including mineral oil from the pancreatin formulation entirely, eliminating the harmful substance while maintaining drug delivery performance through alternative approaches in the enteric-coated micropellet design
Solution Approach 2:
The patent employs alternative substances as intermediaries to replace the functional role of mineral oil in drug delivery, using safe excipients that achieve similar delivery performance without the health concerns associated with synthetic oils
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 enteric-coated formulation achieves controlled release and enhanced gastric acid resistance, maintaining therapeutic efficacy and stability at pH levels relevant to the duodenum, while adhering to regulatory guidelines by excluding restricted excipients.
Implementation Method 1
Controlled or delayed release pharmaceutical compositions for acid-labile drugs, in particular for acid-labile drugs that need to be delivered to the upper intestine of a mammal and where exposure of the acid-labile API to the acidic gastric environment is to be avoided
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.