Amorphous TYK2 Inhibitor Formulations for Stable Extended Release

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Solution Overview

Problem

Existing formulations of BMS-986165, a Tyk2 inhibitor, face challenges in providing sufficient bioavailability and stability, especially when co-administered with gastric pH-raising medications and in low-water regions of the gastrointestinal tract, and require extended-release formulations.

Innovation Solution

Formulations of amorphous BMS-986165 in a polymer matrix, such as HPMCAS, provide improved bioavailability and stability, allowing for both immediate and extended-release dosage forms that maintain solubility and prevent crystallization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If crystalline BMS-986165 formulations are used, then physical stability is improved, but bioavailability deteriorates under elevated gastric pH conditions

Engineering Contradiction:

Improvephysical stabilityVSAvoidbioavailability

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent transforms the crystalline solid form of BMS-986165 into an amorphous solid dispersion, fundamentally changing the physical state and dissolution properties of the drug. This parameter change enables the drug to maintain bioavailability under elevated gastric pH conditions while achieving acceptable physical stability through proper formulation with polymers such as HPMCAS.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system by dispersing amorphous BMS-986165 within a polymer matrix (e.g., HPMCAS). This composite approach combines the drug with excipients that provide structural support and stability, allowing the amorphous form to be stabilized while maintaining its superior dissolution and bioavailability characteristics.

Inventive Principle:

Principle #40Composite materials

2Reliability

If amorphous formulations are used, then bioavailability is improved, but physical stability deteriorates

Engineering Contradiction:

ImprovebioavailabilityVSAvoidphysical stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent stabilizes the amorphous form by incorporating it into a polymer matrix composite. The polymer network physically constrains the drug molecules, preventing them from reorganizing into crystalline structures during storage, thereby maintaining physical stability while preserving the bioavailability advantages of the amorphous state.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent creates localized amorphous regions of BMS-986165 dispersed within the polymer matrix, where each local domain maintains the amorphous state through interactions with surrounding polymer chains. This local quality approach allows the drug to exhibit amorphous properties (high solubility and bioavailability) while the overall formulation achieves stability through the polymer network.

Inventive Principle:

Principle #3Local quality

3Duration of action of moving object

If extended-release formulations are developed, then duration of action is improved, but formulation complexity increases

Engineering Contradiction:

Improveduration of actionVSAvoidformulation complexity

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The amorphous solid dispersion formulation serves multiple functions simultaneously: it enhances bioavailability by improving dissolution rate, enables extended-release kinetics through controlled dissolution, and provides physical stability through the polymer matrix. This multi-functionality reduces the need for separate formulation components designed for each objective, thereby managing complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent achieves extended-release functionality by controlling the dissolution rate parameter of the amorphous drug through selection of specific polymers and formulation conditions. By adjusting polymer type, molecular weight, and composition ratios, the formulation can be tuned to provide sustained release without requiring complex multi-layer or controlled-release device structures.

Inventive Principle:

Principle #35Parameter changes

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 amorphous formulations ensure comparable bioavailability to crystalline forms, even under elevated gastric pH conditions, and offer stable, extended release in low-water GI regions, enhancing treatment efficacy for autoimmune diseases.

Implementation Method 1

Methodology Applied

Scientific EffectAmorphous state stabilization:

Implementation Method 2

allowing for both immediate and extended-release dosage forms that maintain solubility and prevent crystallization

Methodology Applied

Scientific EffectControlled release:

Data Source

PatentUS20260083733A1Dosage forms for TYK2 inhibitors

Publication Date: 2026.03.26 BRISTOL MYERS SQUIBB CO

AI summary

Stable and bioavailable formulations and dosage forms comprising a dispersion (e.g., spray-dried dispersion) of solid amorphous 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (Formula (I); BMS-986165) in a solid polymer matrix are provided for the treatment of auto-immune and auto-inflammatory diseases such as an inflammatory bowel disease (IBD) and psoriasis: