Enteric-Coated Pitolisant Tablets for Reduced Gastric Irritation

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Solution Overview

Problem

Existing pitolisant formulations, such as WAKIX®, cause significant gastric side-effects like nausea, emesis, and upset stomach, leading to poor patient compliance due to intolerance.

Innovation Solution

Development of enteric-coated pitolisant formulations with an anti-moisture barrier and a specific enteric coating, comprising polymers like EUDRAGIT® L 100-55 and OPADRY® amb II, which provide delayed release and minimize gastric irritation, while maintaining bioequivalence to non-enterically coated forms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If non-enterically coated pitolisant formulations are administered, then the drug is rapidly absorbed and provides therapeutic effect, but gastric side-effects such as nausea, emesis, and upset stomach occur significantly

Engineering Contradiction:

Improvetherapeutic effect deliveryVSAvoidgastric side-effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The enteric coating is applied to the tablet core before administration, creating a protective barrier that prevents gastric irritation in advance. The coating is designed to resist dissolution in acidic gastric environment and only dissolve in the more alkaline intestinal environment, thereby preventing nausea, emesis, and upset stomach while ensuring the drug is released at the appropriate location for absorption

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The enteric coating acts as an intermediary layer between the pitolisant drug substance and the gastric environment. This coating layer comprises polymers such as EUDRAGIT® L 100-55 and OPADRY® amb II, which provide a protective interface that prevents direct contact between the irritating drug and the gastric mucosa, thereby eliminating harmful effects while maintaining therapeutic efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If enteric coating is applied to pitolisant formulations, then gastric side-effects are reduced, but delayed release may alter pharmacokinetics and reduce bioequivalence

Engineering Contradiction:

Improvegastric side-effectsVSAvoidbioequivalence

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The enteric coating is formulated with specific polymers (EUDRAGIT® L 100-55 and OPADRY® amb II) and plasticizers to control the dissolution characteristics. The coating is designed to maintain integrity at gastric pH (1.2) and dissolve at intestinal pH (6.8), achieving a balance between protecting against gastric irritation and ensuring timely drug release for absorption. The coating composition and thickness are optimized to prevent excessive delay while maintaining bioequivalence

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The enteric coating comprises a composite formulation combining multiple polymers (EUDRAGIT® L 100-55 and OPADRY® amb II) with plasticizers. This composite structure provides both the necessary gastric resistance and controlled intestinal dissolution properties, ensuring that the drug is protected during gastric transit but released efficiently in the intestine to maintain pharmacokinetic equivalence

Inventive Principle:

Principle #40Composite materials

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 formulations reduce or eliminate gastric side-effects, enhancing patient compliance and ensuring bioequivalence in pharmacokinetic parameters like Cmax, Tmax, and AUC, thus providing effective treatment for sleep disorders like EDS and cataplexy.

Implementation Method 1

an enteric coating that surrounds the core... which provide delayed release and minimize gastric irritation

Methodology Applied

Scientific EffectpH-dependent dissolution:

Implementation Method 2

The dosage form may further comprise an anti-moisture barrier

Methodology Applied

Scientific EffectMoisture barrier:

Data Source

PatentUS20260034114A1Enteric coated pitolisant formulations and methods of use

Publication Date: 2026.02.05 BIOPROJET PHARMA

AI summary

The present disclosure relates generally to dosage forms (e.g., oral dosage forms) and pharmaceutical compositions comprising a pharmaceutically active agent comprising pitolisant or a pharmaceutically acceptable salt, solvate, or hydrate thereof, an enteric coating, and optionally one or more pharmaceutically acceptable excipients; as well as methods of using the dosage forms and pharmaceutical compositions, and methods of making the same.