Darunavir combination formulations

Abstract

This invention relates to solid oral dosage forms of the HIV inhibitor Darunavir and / or a pharmaceutically acceptable salt or solvate thereof, and combination formulations thereof.

Description

FIELD OF THE INVENTION[0001]This invention relates to solid oral dosage forms of the HIV inhibitor darunavir and combination formulations thereof.BACKGROUND OF THE INVENTION[0002]The treatment of Human Immunodeficiency Virus (HIV) infection, known as cause of the acquired immunodeficiency syndrome (AIDS), remains a major medical challenge. HIV is able to evade immunological pressure, to adapt to a variety of cell types and growth conditions and to develop resistance against currently available drug therapies. The latter include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), HIV-protease inhibitors (PIs) and the more recent fusion inhibitors.[0003]Although effective in suppressing HIV, each of these drugs, when used alone, is confronted with the emergence of resistant mutants. This led to the introduction of combination therapy of several anti-HIV agents usually havin...

AI Technical Summary

Benefits of technology

The invention is about a new oral dosage form that contains a lubricant, a disintegrant, and a specific type of silicon dioxide called colloidal silicon dioxide loaded with a certain medication. This new medication is mixed with a powdered ingredient called darunavir to create a granulate. The granulate is then added to a mixture containing microcrystalline cellulose, silicon dioxide, and another ingredient called Hypromellose. This mixture is then compressed to make the final oral dosage form. The oral dosage form is designed to treat HIV infections. The invention was created to improve the stability and bioavailability of the medication.

Problems solved by technology

The treatment of Human Immunodeficiency Virus (HIV) infection, known as cause of the acquired immunodeficiency syndrome (AIDS), remains a major medical challenge.

Although effective in suppressing HIV, each of these drugs, when used alone, is confronted with the emergence of resistant mutants.

However, none of the currently available drug therapies is capable of completely eradicating HIV.

Even HAART may face the emergence of resistance, often due to non-adherence and non-persistence with antiretroviral therapy.

A high pill burden is undesirable for many reasons, such as the frequency of intake, often combined with the inconvenience of having to swallow large dosage forms, as well as the need to store and transport a large number or volume of pills.

A high pill burden increases the risk of patients not taking their entire dose, thereby failing to comply with the prescribed dosage regimen.

As well as reducing the effectiveness of the treatment, this also leads to the emergence of viral resistance.

Because high darunavir dosage forms are inevitably large in size, higher dose or combination dosage forms would take a size that surpasses the convenience barrier.

Higher dose darunavir formulations, dose-proportionally derived from the currently marketed 600-mg tablet, were not deemed desirable for use by patients because of their large size.

Furthermore, the direct compression method led to inferior results when increasing the percentage of darunavir in the formulation.

Inferior results are obtained due to limited gliding and flowing capacity of such a formulation.

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