Amphotericin B Self-Emulsifying Oral Formulation
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Solution Overview
Problem
Current treatments for visceral leishmaniasis and disseminated fungal infections, particularly those involving amphotericin B, face challenges such as low bioavailability, instability in gastric fluid, and renal toxicity, limiting their effectiveness and accessibility due to administration difficulties and high costs.
Innovation Solution
Development of an amphotericin B formulation comprising amphotericin B, fatty acid glycerol esters, and polyethylene oxide-containing fatty acid esters, which forms a self-emulsifying drug delivery system, enhancing bioavailability and stability in gastric and intestinal fluids, allowing for oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If amphotericin B is administered intravenously to achieve high efficacy, then cure rate is improved (97%), but renal toxicity and infusion-related side effects worsen
Solution Approach 1:
The patent uses self-emulsifying carriers comprising fatty acid glycerol esters and polyethylene oxide-containing fatty acid esters as intermediary substances to deliver amphotericin B. These carriers form stable emulsions that protect the drug from direct contact with renal tissues while maintaining therapeutic efficacy, thereby reducing nephrotoxicity associated with conventional IV administration
Solution Approach 2:
The patent changes the physical and chemical parameters of amphotericin B by formulating it in self-emulsifying systems with specific HLB values and molecular weights. This transformation from a water-insoluble compound to a self-emulsifying formulation alters its pharmacokinetic profile, enabling oral administration and reducing dose-limiting renal toxicity
2Ease of operation
If amphotericin B is formulated for oral administration to improve accessibility, then ease of operation is improved, but bioavailability worsens (negligible due to low aqueous solubility)
Solution Approach 1:
The patent fundamentally changes the solubility parameters of amphotericin B by incorporating it into self-emulsifying carriers. These carriers contain fatty acid glycerol esters and polyethylene oxide-containing fatty acid esters with optimized HLB values that enable the formation of fine emulsions in aqueous media, dramatically improving oral bioavailability from negligible to therapeutic levels
Solution Approach 2:
The patent creates composite material systems where amphotericin B is combined with self-emulsifying carriers comprising specific ratios of fatty acid glycerol esters and polyethylene oxide-containing fatty acid esters. This composite formulation enhances aqueous solubility and stability in gastric fluid while maintaining the drug's antifungal activity
3Device complexity
If amphotericin B is administered orally to reduce treatment cost and complexity, then device complexity is reduced, but stability in gastric fluid worsens
Solution Approach 1:
The self-emulsifying carriers act as protective shells that encapsulate amphotericin B molecules. These flexible emulsion structures protect the drug from degradation in the harsh gastric environment (low pH) while allowing controlled release in the intestine, thereby improving stability during oral transit
Solution Approach 2:
The self-emulsifying carriers serve as intermediary protective structures that shield amphotericin B from gastric acid degradation. The carriers' specific composition (fatty acid glycerol esters and polyethylene oxide-containing fatty acid esters) provides a protective microenvironment that maintains drug stability through the gastrointestinal tract
4Reliability
If conventional parenteral formulations are used to ensure efficacy, then cure rate is improved, but ease of operation worsens (difficult route of administration in remote locations)
Solution Approach 1:
The patent inverts the conventional approach by developing an oral formulation instead of continuing with parenteral administration. This inversion makes the treatment suitable for remote locations where IV infrastructure is unavailable, while maintaining efficacy through the self-emulsifying carrier system that ensures adequate bioavailability
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 significantly improves amphotericin B's bioavailability and stability, reducing renal toxicity and enabling effective oral administration, thus expanding treatment access for visceral leishmaniasis and other fungal infections.
Implementation Method 1
forms a self-emulsifying drug delivery system, enhancing bioavailability and stability in gastric and intestinal fluids
Data Source
Figure 1A~1B
Figure 2
Figure 3A
AI summary
The present application relates to an oral formulation of amphotericin B and other therapeutic agents, which formulation comprises one or more fatty acid glycerol esters and one or more PEG modified phospholipids or fatty acid esters. The formulation provides enhanced bioavailability and/or increased stability of the therapeutic agent at the low pH found in gastric fluid.