Flibanserin Extended Release Tablet Formulation
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Solution Overview
Problem
Developing pharmaceutical release systems for flibanserin that provide a pH-independent release profile to improve bioavailability and reduce side effects, as existing systems face challenges due to flibanserin's pH-dependent water solubility, leading to uneven drug release across the gastrointestinal tract.
Innovation Solution
A pharmaceutical release system comprising a therapeutically effective amount of flibanserin, pH-dependent polymers, pH-independent polymers, organic acids, and optional additives, which creates a pH-independent drug release behavior, ensuring consistent release from pH 1-5 and reducing peak plasma concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional pH-independent swelling polymers are used for flibanserin release, then drug release is faster in the stomach, but drug release is slower or incomplete in the small intestine and colon
Solution Approach 1:
The patent applies local quality by using pH-dependent polymers that change their properties at different pH locations in the gastrointestinal tract. The polymers remain insoluble in the acidic stomach (pH 1-3) to prevent premature release, then dissolve in the neutral/basic small intestine (pH 5-8) to enable drug release where needed, creating location-specific release behavior
Solution Approach 2:
The patent utilizes parameter changes by exploiting the pH-dependent solubility characteristics of the polymers. The polymers undergo solubility parameter changes in response to pH variations along the gastrointestinal tract, transitioning from insoluble in acidic environments to soluble in neutral/basic environments, thereby controlling drug release kinetics
2Duration of action of moving object
If pH-dependent retarding polymers are used to slow drug release, then drug release is extended, but the polymers lose their retarding effect above a certain pH
Solution Approach 1:
The patent applies local quality by selecting polymers with specific pH transition points that match the pH environment of different gastrointestinal segments. The polymers provide retarding effects in regions where their solubility is limited, then dissolve when pH exceeds their transition point, creating region-specific release control
Solution Approach 2:
The patent uses composite materials by combining multiple polymers with different pH-dependent properties. This composite approach allows the formulation to maintain controlled release characteristics across a broader pH range, as different polymers contribute their retarding effects at different pH levels
3Object-affected harmful factors
If flibanserin is formulated for extended release to reduce Cmax, then side effects are reduced, but bioavailability may be compromised in pH-variable environments
Solution Approach 1:
The patent exploits parameter changes by using polymers whose solubility parameters change with pH. This allows the formulation to maintain extended release characteristics (reducing Cmax and side effects) while ensuring reliable bioavailability, as the polymers dissolve at appropriate pH levels to release the drug for absorption
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 system achieves a pH-independent bioavailability of flibanserin, allowing for once-daily dosing and reduced side effects by maintaining therapeutic exposure with lower maximum plasma concentrations and extended release profiles.
Implementation Method 1
In acidic environment compounds such as flibanserin are usually very well water soluble whereas in neutral or basic environment these drugs can be practically insoluble. For example, flibanserin shows a solubility of 6.2 mg/ml in 0.1 N HCl and a solubility of 0.002 mg/ml in 0.05 M phosphate buffer pH 6.8.
Implementation Method 2
alginic acids form an insoluble gel layer in acidic environment, but are converted to the soluble sodium alginates at a higher pH
Implementation Method 3
Formulations containing organic acid(s) and a combination of pH-dependent as well as pH-independent retarding polymers as functional excipients provide a pH-independent release profile for a basic compound with pH-dependent solubility such as flibanserin
Data Source
AI summary
The present invention provides pharmaceutical release systems comprising an therapeutically effective amount of flibanserin and at least one pharmaceutically acceptable excipient, characterized in that said pharmaceutical release systems exhibit a pharmacokinetic profile that is characterized by an average maximum flibanserin plasma concentration Cmax lower than 300 ng/mL, preferably lower than 200 ng/mL after administration of a single dose to healthy volunteers in fasted state or directly after a meal.