Amphetamine Bead Coatings for 16-Hour Dosing

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Solution Overview

Problem

Current drug delivery systems for ADHD, such as ADDERALL XR®, require multiple doses due to limited duration of action, necessitating additional short-acting stimulants for extended therapeutic effect, particularly in adults and adolescents with longer waking hours, and face challenges like first-pass metabolism, biological tolerance, and variable gastrointestinal transit times.

Innovation Solution

A novel amphetamine pharmaceutical composition combining immediate release, delayed pulsed release, and sustained release components, with a unique coating structure that includes a delayed release coating layered over a sustained release coating, providing a bioequivalent effect to ADDERALL XR® plus an immediate release dose, ensuring prolonged action up to 14-16 hours without additional supplementation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If a sustained release delivery system is used, then dosing frequency is reduced and patient compliance is improved, but first pass metabolism increases and oral bioavailability decreases

Engineering Contradiction:

Improvedosing frequencyVSAvoidoral bioavailability

Core Design Contradiction:

Duration of action of moving objectVSQuantity of substance

Solution Approach 1:

The drug delivery system is segmented into multiple dosage units (capsules containing multiple pellets), where each unit can be independently designed with different release characteristics. This allows combination of sustained release pellets for extended duration with immediate release pellets for rapid absorption, resolving the contradiction between dosing frequency and bioavailability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different pellets within the same dosage form have different local qualities - some pellets are designed for immediate release while others are designed for sustained release. This local differentiation allows the system to provide both rapid initial absorption (maintaining bioavailability) and extended duration of action (reducing dosing frequency).

Inventive Principle:

Principle #3Local quality

2Measurement precision

If a pulsed dose formulation is used, then specific time period release is achieved, but lag time and rapid release are conflicting hurdles that are hard to optimize

Engineering Contradiction:

Improverelease timing controlVSAvoidformulation complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The formulation is segmented into multiple pellets with different coating characteristics. Some pellets have enteric coatings for delayed release while others have different coatings for immediate release. This segmentation allows independent optimization of lag time and rapid release characteristics without increasing overall formulation complexity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Instead of trying to create a single complex pellet that provides both lag time and rapid release, the invention inverts the approach by using multiple simple pellets with different release characteristics. The combination of these simple pellets achieves the complex release profile without the complexity of individual pellet design.

Inventive Principle:

Principle #13The other way round (Inversion)

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 delivers a pharmacokinetic profile similar to a 2-dose regimen of ADDERALL XR® plus immediate release amphetamine, offering sustained therapeutic effects for ADHD patients with longer-day demands, maintaining bioavailability and efficacy across varying gastrointestinal conditions and food intake states.

Implementation Method 1

The enteric materials, which are soluble at higher pH values, are frequently used for colon-specific delivery systems.

Methodology Applied

Scientific EffectpH-dependent dissolution:

Implementation Method 2

A retarding, swellable hydrophilic coating has been used for oral delayed release systems

Methodology Applied

Scientific EffectHydrogel formation: Hydrogel

Implementation Method 3

A sustained-release drug delivery system is described in U.S. Pat. No. 4,871,549. When this system is placed into dissolution medium or the gastrointestinal tract, water influx and the volume expansion of the swelling agent cause the explosion of the water permeable membrane.

Methodology Applied

Scientific EffectSwelling:

Implementation Method 4

The OROS® push-pull system (Alza Company) has been developed for pulsatile delivery of water-soluble and water-insoluble drugs based on the swelling properties of an osmotic core compartment which provides a pH-independent, time-controlled drug release.

Methodology Applied

Scientific EffectOsmosis: Osmosis

Implementation Method 5

Methodology Applied

Scientific EffectOsmotic pressure: Osmotic Pressure

Data Source

PatentEP2023900B1Controlled dose drug delivery system

Publication Date: 2014.12.24 SHIRE PLC

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AI summary

A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising a pharmaceutically active amphetamine salt covered with an immediate-release coating and a pharmaceutically active amphetamine salt covered with an enteric coating wherein the immediate release coating and the enteric coating provide for multiple pulsed dose delivery of the pharmaceutically active amphetamine salt. The product can be composed of either one or a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.