Stemospironine Salts and Polymorphs for Solubility

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Solution Overview

Problem

There is a need for new salts and polymorphs of stemospironine with improved solubility and bioavailability properties to enhance its effectiveness as a pharmaceutical antitussive agent.

Innovation Solution

Development of stemospironine salts and polymorphs, including hydrochloride and free base forms, characterized by specific X-ray powder diffraction patterns, using acids such as hydrogen chloride, tartaric acid, and sulfuric acid, and methods for their preparation, which improve solubility and bioavailability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If new salts and polymorphs of stemospironine are developed to improve solubility and bioavailability, then therapeutic effectiveness is enhanced, but the complexity of the pharmaceutical formulation increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by developing multiple salts (hydrochloride, hydrobromide, sulfate, tartrate) and polymorphs of stemospironine to systematically improve solubility and bioavailability parameters. Each salt and polymorph represents a controlled variation in chemical and physical parameters that enhances therapeutic effectiveness while providing options to manage formulation complexity.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite materials by combining stemospironine with different counterions to form distinct salt compounds. These composite salts (e.g., stemospironine hydrochloride, stemospironine sulfate) offer tailored solubility profiles and stability characteristics, allowing optimization of therapeutic effectiveness without requiring complex formulation strategies.

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If multiple salts and polymorphs are synthesized to optimize bioavailability, then solubility properties are improved, but the manufacturing process becomes more complex

Engineering Contradiction:

ImprovesolubilityVSAvoidmanufacturing process

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent segments the development process by isolating and characterizing individual salts and polymorphs separately. Each salt form (hydrochloride, hydrobromide, sulfate, tartrate) and polymorph is independently synthesized, purified, and characterized, allowing for systematic optimization of solubility without requiring simultaneous management of multiple complex processes.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs parameter changes through controlled synthesis conditions for each salt and polymorph form. By adjusting reaction parameters such as solvent selection, temperature, and pH during synthesis, the patent optimizes solubility characteristics while maintaining manageable manufacturing processes for each distinct form.

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 new salts and polymorphs of stemospironine exhibit enhanced solubility and bioavailability, optimizing therapeutic administration and cough control as an antitussive agent.

Implementation Method 1

stemospironine salts of Formula 1 wherein HX represents hydrogen chloride, hydrogen bromide, L-tartaric acid, D-tartaric acid, sulfuric acid, (+)-(1S)-10-camphorsulfonic acid, ethanesulfonic acid and ethane-1,2-disulfonic acid

Methodology Applied

Scientific EffectSalt formation: Chemical Bonding

Implementation Method 2

Each crystalline salt is characterized by peaks appearing in its X-ray powder diffraction (XRPD) pattern

Methodology Applied

Scientific EffectX-ray diffraction: X-Ray

Implementation Method 3

characterized by the peaks appearing in its X-ray powder diffraction (XRPD) pattern

Methodology Applied

Scientific EffectDiffraction: Diffraction

Data Source

PatentUS11414427B2Solid forms of stemospironine and its salts

Publication Date: 2022.08.16 YE YANG

AI summary

Disclosed are stemospironine salts of Formula 1: wherein HX represents HCl, HBr, L-tartaric acid, D-tartaric acid, sulfuric acid, (+)-(1S)-10-camphorsulfonic acid, ethanesulfonic acid and ethane-1,2-disulfonic acid. This invention also provides crystalline polymorph forms of the compound of Formula 1 wherein HX is HCl, stemospironine hydrochloride. This invention also provides a new crystalline form of the compound of Formula 2, stemospironine free base: Also disclosed are compositions containing one or more compounds of Formula 1, methods for controlling cough comprising administering a therapeutically effective amount of a compound of Formula 1, and methods for preparing compounds of Formula 1. Also disclosed is a method for preparing crystalline stemospironine hydrochloride polymorph Form II from stemospironine hydrochloride polymorph Form I.