Darunavir combination formulations

a combination formulation and darunavir technology, applied in the field of darunavir combination formulations, can solve the problems of resistance, resistance, resistance, etc., and achieve the effect of less frequen

Inactive Publication Date: 2014-05-22
GILEAD SCI INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0017]The present invention thus provides anti-HIV therapy involving the administration of darunavir dosage forms of acceptable size, potentially as a combinat

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

Method used

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  • Darunavir combination formulations
  • Darunavir combination formulations

Examples

Experimental program
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Effect test

example 1

Darunavir Granulation

1: Granulation

[0068]A high dose formulation, e.g. 800-mg darunavir formulation, dose-proportionally derived from the currently marketed 600-mg tablet, was not perceived as suitable for use by patients because of its large size. Furthermore, direct compression of an 800 mg formulation proved not possible due to severely limited gliding and flowing capacity. The formulations studied are shown in Table 3.

TABLE 3Formulations used in concept feasibility testingABCIngredientsmg / tab%mg / tab%mg / tab%darunavir867.2869.38867.2872.27867.2872.27MCCa——287.1223.93——HPMC 2910————24.002.0015 mPa · sPurified waterb——1043 μl—600 μl—Prosolv HD90337.0826.97—266.7222.23Crospolyvidone25.012.0036.003.0036.003.00Colloidal11.380.913.600.30——anhydroussilicaMagnesium9.250.746.000.506.000.50stearateTotal125010012001001200100aMCC = Microcrystalline Cellulose (Avicel PH101)bPurified water does not appear in the final product

Direct Compression Formulation A:

[0069]All ingredients, except magnesi...

example 2

Darunavir GS-9350 Co-Formulation

2.1 Preparation of Darunavir Granulate

[0094]A binder solution was prepared analogous to wet granulation form C.

[0095]The quantitative and qualitative composition of 1000 mg representative darunavir granulate as obtained by the described process is provided in Table 14.

TABLE 14Quantitative and Qualitative Composition of darunavir granulesComponentQuantity (mg)darunavir ethanolate985.00Hypromellose 2910 15 mPa · s15.00Purified watera374.79Total1,000aRemoved during processing

2.2 Oral Dosage Forms Comprising Darunavir and GS-9350

2.2.1 For Darunavir / GS-9350 Eq. 800 / 150-mg Oral Film Coated Tablets (I):

[0096]1. 14.97 kg of the dried darunavir granules was sieved through an appropriate screen together with 4.896 kg GS-9350 loaded on colloidal silicon dioxide, 2.846 kg silicified microcrystalline cellulose, 1.897 kg microcrystalline cellulose and 765 g crospovidone[0097]2. Mixture was collected in a suitable blender and mixed until homogeneous[0098]3. 127.5 g ...

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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...

Claims

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Application Information

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IPC IPC(8): A61K31/635A61K9/20A61K9/28
CPCA61K31/635A61K9/28A61K9/2095A61K9/1652A61K9/2054A61K9/2009A61K31/5377A61P31/00A61P31/18A61P37/04A61K2300/00
Inventor DELAET, URBAIN ALFONS CHEYNS, PHILIP ERNA H.JANS, EUGEEN MARIA JOZEFMERTENS, ROEL JOS M.VAN DER AVOORT, GEERT
Owner GILEAD SCI INC
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