Stable Topical Oxaborolan Formulation via BHT Removal

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Solution Overview

Problem

Current topical formulations of (R)-4-(5-(4-methoxy-3-propoxyphenyl)pyridin-3-yl)-1,2-oxaborolan-2-ol are chemically and physically unstable, limiting their effectiveness in treating inflammatory disorders such as atopic dermatitis and psoriasis.

Innovation Solution

A topical formulation comprising (R)-4-(5-(4-methoxy-3-propoxyphenyl)pyridin-3-yl)-1,2-oxaborolan-2-ol, hexylene glycol, white petrolatum, mono- and di-glycerides, and paraffin wax, essentially free of butylated hydroxytoluene, which improves chemical and physical stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional topical formulations containing (R)-4-(5-(4-methoxy-3-propoxyphenyl)pyridin-3-yl)-1,2-oxaborolan-2-ol are prepared, then the formulation can be manufactured, but the formulation exhibits chemical and physical instability with phase separation and degradation

Engineering Contradiction:

Improveformulation stabilityVSAvoidchemical and physical stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent modifies the formulation composition by removing BHT and adjusting the ratios of excipients (increasing petrolatum to 70-80%, modifying glycol concentration to 2-10%, and adjusting emulsifier levels). These parameter changes in the formulation composition resolve the instability issue while maintaining manufacturing feasibility.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent removes BHT (butylated hydroxytoluene) from the formulation, extracting the problematic component that was contributing to chemical instability and degradation. This extraction eliminates the harmful effect while the remaining excipients maintain formulation stability.

Inventive Principle:

Principle #2Taking out (Extraction)

2Object-affected harmful factors

If BHT is included in the formulation to prevent oxidation, then antioxidant protection is provided, but chemical degradation and phase separation occur

Engineering Contradiction:

Improveoxidation protectionVSAvoidformulation stability

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent converts the harmful effect of BHT-induced degradation into a benefit by completely removing BHT from the formulation. The harm caused by BHT (chemical degradation and phase separation) is eliminated, and the formulation achieves stability through alternative excipient combinations that do not provoke degradation reactions.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Ease of operation

If the formulation is designed for topical application, then therapeutic effect can be achieved, but manufacturing robustness is compromised due to instability

Engineering Contradiction:

Improvetopical application effectivenessVSAvoidmanufacturing robustness

Core Design Contradiction:

Ease of operationVSEase of manufacture

Solution Approach 1:

The patent adjusts manufacturing parameters by defining specific concentration ranges for excipients (petrolatum 70-80%, glycol 2-10%, emulsifiers 1-5%) that ensure both manufacturing robustness and formulation stability. These parameter specifications make the formulation easy to manufacture consistently while maintaining therapeutic effectiveness.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20230310472A1Stable Topical Formulations of 1(R)-4-(5-(4-Methoxy-3-Propoxphenyl)Pyridin-3-YL)-1,2-OX-Aborolan-2-OL

Publication Date: 2023.10.05 PFIZER INC

AI summary

The present invention relates to the discovery of chemically and physically stable topical formulations comprising (R)-4-(5-(4-methoxy-3-propoxyphenyl)pyridin-3-yl)-1,2-oxaborolan-2-ol (PF-07038124) for treating inflammatory disorders and to methods of preparing the topical formulations.