Romidepsin Liquid Formulation pH Optimization
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Solution Overview
Problem
Current cancer treatments lack effective therapies for various types of cancers, particularly hematological malignancies and solid tumors, with romidepsin showing promise but requiring improved formulations for better solubility and efficacy.
Innovation Solution
Development of liquid formulations of romidepsin with specific ratios of propylene glycol, ethanol, and citrate or acetate buffers, maintaining a pH range of 3.0 to 6.0 or 2.0 to 6.0, respectively, to enhance solubility and therapeutic effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If romidepsin is formulated with traditional solvents, then solubility is improved, but therapeutic effectiveness is reduced
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range (3.0-6.0 for citrate buffer, 2.0-6.0 for acetate buffer) and adjusting the concentration ratios of propylene glycol, ethanol, and buffer components. These parameter modifications enable romidepsin to achieve both high solubility and maintained therapeutic effectiveness, resolving the contradiction between solubility improvement and effectiveness preservation
Solution Approach 2:
The patent uses a composite solvent system combining propylene glycol, ethanol, and citrate or acetate buffer in specific ratios. This composite formulation leverages the solubilizing properties of multiple components while the buffer system maintains pH conditions that preserve romidepsin's therapeutic activity, thus resolving the contradiction between enhanced solubility and maintained effectiveness
2Reliability
If romidepsin concentration is increased, then anticancer activity is enhanced, but solubility limitations are exceeded
Solution Approach 1:
The patent employs parameter changes by adjusting the pH to optimal ranges (3.0-6.0 or 2.0-6.0) and modifying the solvent composition ratios to enable higher romidepsin concentrations (up to 10 mg/mL) to be dissolved while maintaining the drug's anticancer activity. This resolves the contradiction between achieving therapeutic concentration and overcoming solubility limits
3Stability of the object's composition
If pH is adjusted to improve solubility, then formulation stability is improved, but drug efficacy may be compromised
Solution Approach 1:
The patent applies parameter changes by identifying and implementing optimal pH ranges (3.0-6.0 for citrate buffer formulations, 2.0-6.0 for acetate buffer formulations) that simultaneously ensure formulation stability and preserve romidepsin's anticancer efficacy. The buffer systems are specifically selected to maintain these pH ranges, resolving the contradiction between stability improvement and efficacy preservation
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 formulations provide a therapeutically effective concentration of romidepsin, improving its solubility and stability, thereby enhancing its anticancer activity against a range of cancers, including hematological malignancies and solid tumors.
Implementation Method 1
a citrate buffer, wherein the ratio of PG, EtOB and the citrate buffer is 70% of PG, 20% of EtOH, and 10% of the citrate buffer, wherein the pH of the formulation is in a range between 3.0 and 6.0
Implementation Method 2
propylene glycol (PG); ethanol (EtOH); and a citrate buffer, wherein the ratio of PG, EtOB and the citrate buffer is 70% of PG, 20% of EtOH, and 10% of the citrate buffer
Data Source
AI summary
Provided herein are liquid concentrate formulations of romidepsin. Also provided are methods for producing these formulations and uses thereof. In one embodiment, the formulation comprises romidepsin, polyethylene glycol, etanol and a citrate buffer. In another embodiment, the formulation comprises romidepsin, polyethylene glycol, etanol and an acetate buffer.