Low-Excipient HIV Tablet Formulation With Stable TAF and Emtricitabine
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pharmaceutical formulations for treating HIV, particularly those containing tenofovir alafenamide and emtricitabine, face challenges in achieving stability and require a significant amount of excipients, which can be burdensome for patients and affect compliance.
Innovation Solution
Formulating tablets with only two active pharmaceutical ingredients, tenofovir alafenamide and emtricitabine, in a stable composition that reduces the total amount of excipients, ensuring stability and bioequivalence with existing medicines, while optimizing pharmacokinetic parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing pharmaceutical formulations containing tenofovir alafenamide and emtricitabine are used, then therapeutic efficacy is achieved, but the amount of excipients required is significant, affecting patient compliance
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using tenofovir alafenamide hemifumarate in a specific concentration range (5-15% w/w) and controlling the polymorphic form (Form I), which enables reduced excipient content while maintaining stability and efficacy. This parameter optimization allows the formulation to achieve therapeutic goals with fewer excipients.
Solution Approach 2:
The patent creates a composite pharmaceutical formulation by combining tenofovir alafenamide hemifumarate with emtricitabine in specific ratios, along with optimized excipient selection. This composite approach allows for reduced overall excipient burden while maintaining the stability and efficacy of both active ingredients through their synergistic interaction in the combined formulation.
2Stability of the object's composition
If the concentration of tenofovir alafenamide is increased to improve stability, then stability is enhanced, but degradation products may increase
Solution Approach 1:
The patent optimizes the concentration parameter of tenofovir alafenamide hemifumarate within a specific range (5-15% w/w) and controls the physical form parameter (polymorphic Form I). This parameter optimization achieves enhanced stability while minimizing degradation product formation by avoiding both excessive concentration and unstable polymorphic forms.
Solution Approach 2:
The patent uses emtricitabine as an intermediary substance that interacts with tenofovir alafenamide hemifumarate in a controlled manner. This intermediary relationship helps stabilize the formulation and reduce degradation of tenofovir alafenamide, thereby minimizing harmful degradation products while maintaining high stability.
3Stability of the object's composition
If multiple excipients are added to ensure stability, then stability is improved, but patient compliance deteriorates due to excipient burden
Solution Approach 1:
The patent changes the formulation parameters by using tenofovir alafenamide hemifumarate at optimized concentrations (5-15% w/w) and controlling the polymorphic form, which inherently provides stability without requiring multiple excipients. This parameter-optimized approach reduces the excipient burden while maintaining stability, thereby improving patient compliance.
Solution Approach 2:
The patent extracts and eliminates unnecessary excipients from the formulation by relying on the inherent stability of tenofovir alafenamide hemifumarate in its optimized concentration range and polymorphic Form I. This extraction of redundant components reduces the excipient burden while preserving essential stability, making the formulation more acceptable to patients.
Data Source
Figure 1
Figure 2A~2B
Figure 3
AI summary
The invention provides a solid oral dosage form comprising tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and emtricitabine or a pharmaceutically acceptable salt thereof.