RK-33 Intravenous Formulation Using Cholic Acid Micelles
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Solution Overview
Problem
The challenge of delivering RK-33 through intravenous administration is hindered by its intrinsic solubility issues, lacking a stable formulation for effective chemotherapy delivery.
Innovation Solution
A liquid formulation comprising RK-33, cholic acid or its derivative, a water-soluble polyvinyl polymer, and water, stabilized through milling to achieve an aqueous suspension suitable for intravenous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If RK-33 is formulated for intravenous administration, then drug delivery effectiveness is improved, but solubility stability deteriorates due to intrinsic solubility issues
Solution Approach 1:
The patent employs cholic acid and polyvinylpyrrolidone as intermediary substances that mediate between RK-33 and the aqueous environment. Cholic acid forms mixed micelles with the polymer, creating a stable interface that solubilizes RK-33 without requiring the drug to directly interact with water, thus resolving the solubility-stability contradiction
Solution Approach 2:
The formulation creates a composite system combining cholic acid, polyvinylpyrrolidone, and RK-33 in specific ratios. This composite approach leverages the amphiphilic properties of cholic acid and the water solubility of the polymer to achieve both intravenous administrability and compositional stability
2Reliability
If RK-33 is administered intravenously, then treatment efficacy is improved, but particle aggregation increases leading to precipitation
Solution Approach 1:
The patent optimizes critical parameters including the ratio of cholic acid to polyvinylpyrrolidone (0.1:0.9 to 0.5:0.5), RK-33 concentration (1-30 mg/mL), and particle size (D50: 0.05-0.5 μm). These parameter adjustments control the balance between maintaining treatment efficacy and preventing harmful particle aggregation during storage and administration
3Reliability
If RK-33 concentration is increased in formulation, then treatment effectiveness is improved, but formulation stability deteriorates
Solution Approach 1:
The polyvinylpyrrolidone-cholic acid complex serves multiple functions simultaneously: it solubilizes high concentrations of RK-33, stabilizes the formulation during storage, controls particle size, and prevents aggregation. This multi-functionality allows the formulation to maintain stability even at high drug concentrations (1-30 mg/mL)
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 a stable, chemically and physically stable aqueous suspension of RK-33, minimizing particle aggregation and enabling effective intravenous delivery without precipitation.
Implementation Method 1
comprising RK-33, cholic acid or derivative thereof, a water-soluble polyvinyl polymer, and water
Implementation Method 2
stabilized through milling to achieve an aqueous suspension
Data Source
AI summary
The present disclosure provides a liquid formulation comprising: (a) RK-33, (b) cholic acid or derivative thereof, (c) a water-soluble polyvinyl polymer, and (d) water. The disclosure also provides a method of making a liquid formulation comprising RK-33. The disclosure further provides a method of treating cancer in a subject in need thereof, the method comprising (a) diluting the formulation of the present disclosure to form a diluted formulation, and (b) intravenously administering to the subject the diluted formulation.