Multi-Layered Anti-Tubercular Tablet Segregating Rifampin and Isoniazid
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-tubercular pharmaceutical compositions face challenges with stability and bioavailability, particularly due to the degradation of rifampin in the presence of isoniazid, leading to reduced effectiveness and increased drug resistance.
Innovation Solution
A film-coated, multi-layered preparation process for rifampin, isoniazid, pyrazinamide, and ethambutol hydrochloride is developed, where rifampin and isoniazid are in separate layers, with each drug individually mixed with excipients and granulated, and then compressed into distinct layers to prevent degradation and enhance bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If rifampin and isoniazid are mixed together in the same formulation, then the treatment is simplified and patient compliance is improved, but the bioavailability of rifampicin is reduced due to degradation caused by isoniazid
Solution Approach 1:
The tablet is divided into multiple layers with rifampicin and isoniazid separated into different layers. This physical segmentation prevents direct contact between the two drugs, eliminating the degradation reaction while maintaining the benefits of fixed-dose combination therapy.
Solution Approach 2:
Different layers of the tablet have different properties - the rifampicin layer and isoniazid layer are kept distinct with different local compositions. This allows each drug to maintain its stability and bioavailability characteristics locally while being delivered together in a single tablet.
2Ease of manufacture
If rifampin and isoniazid are formulated in the same layer, then the manufacturing process is simplified, but the stability of rifampin is compromised due to chemical degradation
Solution Approach 1:
The formulation is segmented into multiple layers during the manufacturing process. Rifampicin and isoniazid are placed in separate layers, preventing chemical interaction while maintaining a relatively simple compressed tablet structure that is easy to manufacture.
Solution Approach 2:
The tablet structure itself acts as an intermediary barrier between rifampicin and isoniazid. The physical separation provided by the layered structure prevents direct chemical contact while allowing both drugs to be administered together in a single dosage form.
3Ease of operation
If a fixed-dose combination of four drugs is used, then the number of tablets is reduced and compliance is improved, but drug resistance may still develop due to partial compliance
Solution Approach 1:
The four-drug combination is formulated as a single multi-layered tablet, reducing the number of tablets from four to one. This significantly improves patient compliance while the stable formulation ensures all drugs are released as intended, reducing the risk of partial compliance and drug resistance.
Solution Approach 2:
The tablet uses a composite layered structure where each layer contains specific drugs in fixed proportions. This composite formulation ensures that all four anti-tubercular drugs are delivered together in the correct ratios, maintaining effective treatment and preventing drug resistance.
Data Source
AI summary
This invention relates to a process for preparing a pharmaceutical composition comprising four antitubercular drugs: rifampin or a pharmaceutically acceptable salt thereof, isoniazid or a pharmaceutically acceptable salt thereof, pyrazinamide or a pharmaceutically acceptable salt thereof and ethambutol or a pharmaceutically acceptable salt thereof, wherein rifampin and isoniazid are in separate layers. The invention also provides a pharmaceutical composition prepared therefrom having advantageous stability and bioavailability.