Hepalatide Formulation Using Phosphate Buffer and Mannitol
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Solution Overview
Problem
Hepalatide, a polypeptide drug derived from the HBV large surface protein, poses challenges in formulation due to its hydrophobic nature, making it difficult to create a water-soluble form, which is essential for effective drug delivery, as it is hardly soluble in water but readily soluble in organic solvents, and existing formulations struggle with stability and re-dissolution post-lyophilization.
Innovation Solution
A drug formulation comprising Hepalatide in a phosphate buffer salt with an osmotic regulator and/or excipient, specifically using a combination of mannitol and NaCl, which improves solubility and stability, allowing for a concentration range of 0.1 mg/ml to 8.0 mg/ml to ensure clarity and effectiveness in injection form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Hepalatide is formulated in water, then solubility is improved, but stability deteriorates due to hydrophobic nature
Solution Approach 1:
The patent introduces buffer salts (phosphate or carbonate) as intermediary substances that mediate between the hydrophobic Hepalatide and water. These buffer salts create a stable aqueous environment that accommodates the hydrophobic polypeptide, resolving the contradiction between water solubility and stability. The buffer system acts as a bridge, allowing Hepalatide to maintain both solubility and stability in the formulation.
2Reliability
If concentration is increased to improve efficacy, then effectiveness is improved, but solubility deteriorates
Solution Approach 1:
The patent employs parameter changes by systematically optimizing the concentration ranges of multiple formulation components: Hepalatide (0.1-50 mg/ml), buffer salts (0.001M-0.5M), osmotic regulators (0-500 mM), and excipients (0-20%). By adjusting these parameters within specific ranges, the formulation achieves both high effectiveness through increased Hepalatide concentration and maintained solubility through coordinated optimization of other components.
3Stability of the object's composition
If lyophilization is performed to improve storage stability, then storage stability is improved, but re-dissolution capability deteriorates
Solution Approach 1:
The patent applies preliminary action by incorporating excipients (mannitol, dextran, sorbitol, lactose, or polyethylene glycol) into the formulation before lyophilization. These excipients are pre-added to protect the Hepalatide structure and maintain its ability to re-dissolve after lyophilization. The excipients act as stabilizers that preserve re-dissolution capability during the lyophilization process, preventing the deterioration that would otherwise occur.
4Stability of the object's composition
If buffer salt concentration is increased to improve stability, then stability is improved, but osmotic pressure increases causing discomfort
Solution Approach 1:
The patent merges multiple functions into a single buffer salt system that simultaneously provides stability and osmotic pressure control. By selecting phosphate or carbonate buffer salts and optimizing their concentration (0.001M-0.5M), the formulation achieves both stability and acceptable osmotic pressure in one component system, rather than treating these as separate issues requiring separate additives.
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 achieves improved solubility, stability, and re-dissolution properties, enabling effective HBV infection blocking and meeting clinical use requirements, with the Hepalatide concentration range ensuring clarity and efficacy in the final product.
Implementation Method 1
A drug formulation comprising Hepalatide in a phosphate buffer salt with an osmotic regulator and/or excipient
Implementation Method 2
specifically using a combination of mannitol and NaCl, which improves solubility and stability
Implementation Method 3
a lyophilized drug formulation prepared from the above drug formulation or sterile drug formulation via lyopilization
Data Source
AI summary
The present disclosure provides a drug formulation for hepalatide, comprising hepalatide and a buffer salt, and containing or not containing an osmotic regulator and/or an excipient.