Combination Therapy for Use in Treating Retroviral Infections

Abstract

A pharmaceutical composition is provided comprising combination of antiretroviral drugs optionally in combination of pharmacokinetic boosters. The formulation is used for the treatment of diseases caused by retroviruses. The process of preparation of the formulation is also provided.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of and claims priority to U.S. patent application Ser. No. 16 / 606,021, filed Oct. 17, 2019 and published as U.S. Patent Application Publication No. 2020 / 0046701 A1, which is a filing under 35 U.S.C. 371 of International Application No. PCT / IN2018 / 050229 filed Apr. 18, 2018, entitled “Combination Therapy for Use in Treating Retroviral Infections” which claims priority to Indian Provisional Patent Application Serial Number 201721013733 filed on Apr. 18, 2017 which applications are incorporated by reference herein in their entirety.FIELD OF INVENTION[0002]The present invention relates to pharmaceutical composition comprising at least one antiretroviral agent and optionally at least one pharmacokinetic booster or enhancer and optionally at least one pharmaceutically acceptable excipients. The present invention also provides manufacturing processes thereof and use of the said composition for prevention, treat...

AI Technical Summary

Benefits of technology

The combination therapy achieves higher bioavailability and reduced side effects, maintaining optimal drug concentrations, and simplifies dosing, thereby enhancing treatment efficacy and patient compliance, particularly for HIV infection, and addressing resistance issues.

Problems solved by technology

HIV kills the CD4 positive immune cells that it infects, thereby crippling the immune system.

Although the use of combination drug therapies against HIV has proven to be effective in many patients, the current drug regimens are far from ideal.

Treatment failure often (though not always) occurs because a patient's strain of HIV may develop resistance to one or more of antiretroviral medications.

These mutant strains then replace the wild-type strain due to their selective replication advantage in the face of drug pressure, leading to treatment failure.

This is rather a demanding task for HIV infected patients due to various reasons such as low morale, social stigma, low immunity attributed to the disease.

Some studies have also shown that adherence to prescribed drugs over long treatment periods is generally poor.

Hence, such non-adherence may lead to rebound in viral replication and, in presence of sub-optimal drug concentration may lead to rapid development of drug resistance.

This development of drug resistance may be disastrous because of the complexity and cost associated with second line regimens and the potential for transmission of drug resistant virus in the community.

The therapy may involve use of different drug combinations, which are difficult to adhere, because of the different dosage forms for administering each such antiretroviral drug separately.

Although HIV-1 infection can be cured by cocktail of drugs offered as highly active antiretroviral therapy (HAART), but the emergence of resistant human immunodeficiency virus has created a new challenge to combat the adverse situation of the disease.

Resistance in the strains is a major cause of failure of antiretroviral therapy that may ultimately compromise the antiretroviral's efficacy in general population.

In most cases, resistance is due to poor adherence by the patient and / or to low potency of the therapeutic regimen.

The combination of long treatment and side effects results in poor compliance, which is a major contributor to the development of resistance.

When a pharmacokinetic booster or enhancer is coadministered with an antiretroviral drug, the pharmacokinetic enhancer interferes with the breakdown of the anti-retroviral drug, which causes the anti-retroviral drug to remain in the body for a longer time and at a higher concentration.

However, many patient groups such as the elderly, children, and patients who are mentally retarded, uncooperative, nauseated, or on reduced liquid-intake / diets have difficulties swallowing the dosage forms such as tablets and hard gelatin capsules.

Further, those who are traveling or have little access to water are similarly affected.

Especially, the geriatric and pediatric patients experience difficulty in swallowing larger sized tablets wherein large size tablet may result in esophageal damage due to its physical characteristics if it is not swallowed properly, which ultimately leads to poor patient compliance.

Also, oral administration of bitter drugs with an acceptable degree of palatability is a key issue for health care providers, especially for pediatric patients.

However, not all compounds are suitable for administration in combinations as there are several factors that influence the feasibility of combinations such as the chemical instability of the compounds, size of the dosage unit, potential for antagonistic or merely additive activities of the combined compounds, and difficulties in achieving a suitable formulation.

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