High-Concentration Ibrutinib Tablet Formulation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current pharmaceutical compositions of Ibrutinib require multiple capsules or tablets daily, making them inconvenient for patients and lacking a formulation with more than 90% w/w Ibrutinib, which affects ease of swallowing and patient compliance.

Innovation Solution

A tablet composition comprising more than 90% w/w Ibrutinib and minimal pharmaceutically acceptable excipients, optimized for better dissolution and bioavailability, with a process involving blending, granulation, and compression to create a stable and easily manufacturable form.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If multiple capsules or tablets are administered daily to achieve therapeutic dose, then the required Ibrutinib dosage can be met, but patient compliance and convenience deteriorate

Engineering Contradiction:
ImproveIbrutinib dosageVSAvoidPatient compliance
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent combines multiple daily doses of Ibrutinib into a single high-concentration tablet formulation containing more than 90% w/w of the active ingredient. This merging approach allows the total daily therapeutic dose to be administered in one tablet rather than multiple capsules or tablets, thereby improving patient compliance and convenience while maintaining the required dosage quantity.

Inventive Principle:
Principle #5Merging (Combining)

2Weight of stationary object

If high concentration of Ibrutinib (>90% w/w) is formulated in tablet, then tablet size and weight are reduced improving swallowability, but formulation stability and manufacturability may deteriorate

Engineering Contradiction:
ImproveTablet weightVSAvoidFormulation stability
Core Design Contradiction:
Weight of stationary objectVSEase of manufacture

Solution Approach 1:

The patent employs parameter changes by optimizing the concentration of Ibrutinib to more than 90% w/w and carefully selecting and quantifying specific excipients (microcrystalline cellulose 5-15% w/w, croscarmellose sodium 2-5% w/w, magnesium stearate 0.5-2% w/w). This parameter optimization ensures the tablet maintains high concentration while preserving formulation stability, manufacturability, and desired dissolution characteristics.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If high concentration of Ibrutinib (>90% w/w) is formulated in tablet, then patient compliance improves, but dissolution performance may deteriorate

Engineering Contradiction:
ImprovePatient complianceVSAvoidDissolution performance
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent uses excipients as intermediary substances to facilitate dissolution of high-concentration Ibrutinib. Specifically, microcrystalline cellulose (5-15% w/w) acts as a filler and disintegrant, croscarmellose sodium (2-5% w/w) serves as a superdisintegrant, and magnesium stearate (0.5-2% w/w) functions as a lubricant. These intermediaries enable the high-concentration formulation to maintain comparable dissolution performance to marketed formulations while improving patient compliance.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS11576917B2Pharmaceutical compositions comprising Ibrutinib
Publication Date: 2023.02.14 NATCO PHARMA LTD

AI summary

The present invention relates to pharmaceutical compositions comprising Ibrutinib. More particularly, the present invention relates to a tablet composition comprising Ibrutinib and one or more pharmaceutically acceptable excipients and process for preparing such compositions.