Raltegravir Tablet Formulation for Reduced Weight and Variability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current raltegravir tablets, such as Isentress®, have limitations in terms of size, weight, and pharmacokinetic profile, which can affect drug absorption and variability, making them less ideal for fixed-dose combinations and optimal HIV treatment.
Innovation Solution
The development of compressed tablets containing an intragranular component with an alkali metal salt of raltegravir, a first superdisintegrant, and a binder, along with an extragranular component including a second superdisintegrant, filler, and lubricant, without atazanavir, to enhance drug absorption and reduce variability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If current raltegravir tablet formulations are used, then the drug can be administered orally, but the tablet size and weight are large which limits fixed-dose combinations and optimal treatment
Solution Approach 1:
The patent changes the physical and chemical parameters of the tablet formulation by using specific excipients (microcrystalline cellulose, croscarmellose sodium, magnesium stearate) and compression forces to achieve a more compact tablet structure. This allows increasing the drug load while reducing tablet weight through optimized density and composition ratios
Solution Approach 2:
The patent creates a composite tablet formulation by combining raltegravir with multiple excipients in specific ratios. The composite structure integrates the active pharmaceutical ingredient with carriers, disintegrants, and lubricants to achieve both high drug load and reduced tablet weight through optimized material composition
2Reliability
If current raltegravir tablet formulations are used, then the drug can be delivered to patients, but the pharmacokinetic profile shows high variability which affects drug absorption
Solution Approach 1:
The patent applies local quality by using a superdisintegrant (croscarmellose sodium) specifically in the tablet formulation to enhance localized disintegration and dissolution properties. This targeted approach improves drug release at the site of administration, reducing pharmacokinetic variability without affecting other tablet properties
Solution Approach 2:
The patent incorporates preliminary action by pre-mixing the drug with specific excipients in defined ratios before compression. This pre-formulation step ensures uniform distribution of the active ingredient and excipients, leading to consistent dissolution rates and reduced variability in drug absorption
Data Source
Figure 1
AI summary
Compressed tablets for oral administration containing raltegravir in the form of a pharmaceutically acceptable salt are described. The tablets comprise (A) an intragranular component comprising (i) an effective amount of an alkali metal salt of raltegravir, (ii) optionally a first superdisintegrant, and (iii) a binder; and (B) an extragranular component comprising (i) a second superdisintegrant, (ii) a filler, and (iii) a lubricant. Methods for preparing the tablets and the use of the tablets, optionally in combination with other anti-HIV agents, for the inhibition of HIV integrase, for the treatment or prophylaxis of HIV infection, or for the treatment, delay in the onset, or prophylaxis of AIDS are also described.