SHR0302 Topical Formulation pH and DMSO Optimization
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Solution Overview
Problem
Topical pharmaceutical compositions of SHR0302 face challenges in maintaining stability and preventing crystal formation of the active ingredient, particularly at pH levels above 4.6 and with high concentrations of dimethyl sulfoxide.
Innovation Solution
Formulations of SHR0302 with a pH of less than 4.6 and containing 20% to 30% dimethyl sulfoxide exhibit improved stability and prevent crystal formation of the active ingredient, maintaining potency over prolonged storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the pH of the formulation is increased above 4.6, then the solubility of SHR0302 is improved, but crystal formation of the active ingredient occurs during storage
Solution Approach 1:
The patent applies parameter changes by optimizing the pH to be less than 4.6 and controlling the dimethyl sulfoxide concentration between 20-30%, which resolves the contradiction between solubility and stability. This specific parameter range prevents crystal formation while maintaining adequate drug dissolution.
Solution Approach 2:
The patent uses a composite formulation system combining SHR0302 with dimethyl sulfoxide as a co-solvent and various excipients. This composite approach allows the formulation to maintain solubility through the synergistic effect of multiple components while preventing crystallization through the specific pH and composition ranges.
2Quantity of substance
If the concentration of dimethyl sulfoxide is increased to improve solubility, then the dissolution of SHR0302 is enhanced, but crystal formation occurs during storage
Solution Approach 1:
The patent applies parameter changes by optimizing the dimethyl sulfoxide concentration to be between 20-30%, which resolves the contradiction between dissolution enhancement and crystal formation prevention. This specific concentration range provides sufficient solubility while maintaining formulation stability during storage.
3Duration of action of stationary object
If the formulation is stored at controlled room temperature for extended periods, then the shelf life is extended, but potency loss of the active ingredient occurs
Solution Approach 1:
The patent applies preliminary action by pre-optimizing the formulation composition and pH before storage to prevent degradation. The formulation is designed with specific ingredients and pH levels that proactively protect against potency loss during extended storage at room temperature, eliminating the need for refrigeration.
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 improved formulations of SHR0302 demonstrate enhanced stability and shelf life, maintaining the active ingredient's potency and preventing crystal formation, even at controlled room temperature for up to 18 months.
Implementation Method 1
formulations of SHR0302 having a pH of less than 4.6 have improved stability and do not exhibit crystal formation of the active ingredient
Implementation Method 2
formulations comprising a certain percentage of dimethyl sulfoxide have improved stability and do not exhibit crystal formation of the active ingredient
Data Source
AI summary
The disclosure relates to stable topical pharmaceutical compositions of SHR0302 (also known as ARQ-250). In certain embodiments, pharmaceutical compositions of SHR0302 having a pH of less than about 4.6 have improved stability and do not exhibit crystal formation of the API. In certain embodiments, pharmaceutical compositions of SHR0302 comprising about 20% to about 30% dimethyl sulfoxide (DMSO) have improved stability and do not exhibit crystal formation of the API. The improved formulations of SHR0302 can exhibit acceptable commercial product shelf life and do not exhibit loss of potency of the API after prolonged storage.