Hydrocortisone Sodium Phosphate Formulation for Aqueous Stability
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Solution Overview
Problem
Existing formulations of hydrocortisone and hydrocortisone sodium phosphate face challenges in stability, efficacy, and delivery methods, particularly in aqueous solutions, which affect their therapeutic effectiveness and convenience for treating various medical conditions.
Innovation Solution
An aqueous pharmaceutical formulation comprising specific concentrations of hydrocortisone sodium phosphate and monothioglycerol, along with other additives, is developed to enhance stability and therapeutic efficacy, allowing for convenient administration via autoinjector devices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hydrocortisone sodium phosphate is formulated in aqueous solution, then therapeutic efficacy is improved, but stability deteriorates
Solution Approach 1:
The patent introduces a surfactant system comprising sodium lauryl sulfate and polysorbate 80 as intermediary substances that mediate between the hydrocortisone sodium phosphate and the aqueous environment. This surfactant complex prevents direct interaction between the drug and water that would cause degradation, while still allowing the formulation to maintain therapeutic efficacy in aqueous solution.
Solution Approach 2:
The formulation creates a composite system by combining hydrocortisone sodium phosphate with a multi-component surfactant system (sodium lauryl sulfate + polysorbate 80) and buffering agents. This composite approach allows the formulation to simultaneously achieve aqueous solubility for therapeutic efficacy and enhanced stability through the protective surfactant matrix.
2Reliability
If concentration of hydrocortisone sodium phosphate is increased, then therapeutic effectiveness is improved, but solubility deteriorates
Solution Approach 1:
The surfactant system acts as an intermediary that enables high concentrations of hydrocortisone sodium phosphate to be solubilized in aqueous solution. The surfactants form micellar structures that can incorporate the drug at high concentrations while maintaining solubility in the aqueous vehicle.
Solution Approach 2:
The patent changes the chemical parameters of the formulation system by introducing specific surfactants and buffering agents that alter the solubility characteristics of hydrocortisone sodium phosphate, enabling concentration ranges (120-141 mg/mL) that would otherwise be insoluble in aqueous solution.
3Stability of the object's composition
If pH is adjusted to optimize stability, then formulation stability is improved, but drug degradation increases
Solution Approach 1:
The surfactant system serves as a protective intermediary that shields the hydrocortisone sodium phosphate from pH-related degradation. This allows the formulation to maintain stability across a broader pH range (7.0-9.0) without increasing drug degradation, as the surfactants buffer the chemical environment around the drug molecules.
Solution Approach 2:
The formulation uses a composite buffering system comprising multiple components that work synergistically to maintain pH stability while preventing drug degradation. This composite approach allows optimization of both stability and drug integrity simultaneously.
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 formulation provides improved stability, higher exposure, and faster peak serum concentration of hydrocortisone, enhancing therapeutic effectiveness for conditions such as adrenal insufficiency and allergic reactions, and is suitable for emergency use.
Implementation Method 1
monothioglycerol antioxidant
Implementation Method 2
phosphate buffer
Data Source
AI summary
The present disclosure provides aqueous formulations comprising hydrocortisone sodium phosphate and monothioglycerol. In some embodiments, the formulations comprise monobasic sodium phosphate, dibasic sodium phosphate, or disodium EDTA. The present disclosure further provides a method of treating a disease or disorder in a subject by administering the aqueous formulation.