Irinotecan Oral Solid Formulation with Acidifying Agent
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Solution Overview
Problem
Current oral solid formulations of irinotecan suffer from limited bioavailability and stability, leading to reduced efficacy and increased side effects due to rapid deactivation in the gastrointestinal tract.
Innovation Solution
Incorporating an acidifying agent such as acetic acid, citric acid, or lactic acid in the formulation to enhance the dissolution rate and stability of irinotecan, with the acidifying agent being used in amounts ranging from 0.2 to 10 parts by weight based on irinotecan, which improves the oral bioavailability and stability of the active ingredient.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oral solid formulation of irinotecan is developed to enable long-term administration, then efficacy is improved and side effects are reduced, but bioavailability is poor due to rapid deactivation in gastrointestinal tract
Solution Approach 1:
The patent changes the pH parameter of the gastrointestinal environment by incorporating acidifying agents (citric acid, lactic acid, or acetic acid) into the formulation. This pH modification protects irinotecan from rapid deactivation by carboxylesterases, thereby improving bioavailability while maintaining the efficacy benefits of long-term oral administration
2Object-affected harmful factors
If oral solid formulation is used to achieve long-term lower dose administration, then toxicity is reduced, but stability of irinotecan is poor due to rapid metabolism
Solution Approach 1:
The patent applies preliminary action by pre-modifying the gastrointestinal environment with acidifying agents before irinotecan encounters deactivating enzymes. This preliminary pH adjustment creates a protective environment that maintains irinotecan stability throughout the gastrointestinal tract, ensuring sufficient drug reaches the systemic circulation while enabling long-term administration at lower, less toxic doses
3Ease of operation
If conventional oral formulations are used, then administration route is simplified, but dissolution rate is insufficient leading to poor bioavailability
Solution Approach 1:
The patent changes the chemical environment parameter (pH) by incorporating acidifying agents that create an acidic microenvironment during dissolution. This pH modification significantly accelerates the dissolution rate of irinotecan, enabling rapid drug release while maintaining the ease of oral administration. The acidifying agents enhance solubility and dissolution kinetics without complicating the administration route
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 use of acidifying agents significantly increases the dissolution rate and stability of irinotecan, ensuring improved bioavailability and reduced side effects, thereby enhancing the efficacy of oral administration while minimizing adverse effects compared to conventional intravenous administration.
Implementation Method 1
the dissolution rate of the active ingredient, due to including the acidifying agent
Implementation Method 2
the active ingredient of the irinotecan-containing oral solid formulation may also have high stability with time
Data Source
Figure 1~2
Figure 3
AI summary
An oral solid formulation includes irinotecan or a pharmaceutically acceptable salt thereof as an active ingredient, and an acidifying agent.