Design, Formulation and Development of Triple-Combination Bilayer Antiretroviral Tablets

Abstract

Human Immunodeficiency Virus (HIV) remains a major global health challenge, requiring lifelong antiretroviral therapy (ART) for effective disease management. Triple-drug regimens are the standard of care; however, long-term treatment may reduce patient adherence because of pill burden and drug incompatibility. Bilayer tablet technology provides an effective fixed-dose combination approach by separating incompatible drugs while enabling immediate and sustained drug release within a single dosage form. This review highlights the design, formulation strategies, evaluation methods, current developments, challenges, and future prospects of triple-combination bilayer antiretroviral tablets. The technology offers significant potential to improve treatment adherence, therapeutic efficacy, and patient convenience in HIV management.

Introduction

Human Immunodeficiency Virus (HIV) is a chronic viral infection that weakens the immune system by attacking CD4? T lymphocytes and can progress to Acquired Immunodeficiency Syndrome (AIDS) if left untreated. Although combination antiretroviral therapy (ART), particularly triple-drug regimens, effectively suppresses viral replication and improves patient survival, lifelong treatment often results in high pill burden, complicated dosing schedules, and poor patient adherence.

Triple-combination bilayer tablets offer a promising solution by combining multiple antiretroviral drugs into a single dosage form with both immediate and controlled drug release. This technology reduces drug–drug incompatibility, improves stability, simplifies treatment, enhances patient compliance, and supports better long-term therapeutic outcomes in HIV management.

The development of bilayer tablets requires careful selection of active pharmaceutical ingredients (APIs) based on their compatibility, stability, and pharmacokinetic properties. Preformulation studies using techniques such as FTIR, DSC, XRD, and micromeritic analysis help ensure formulation quality. Tablets are manufactured through direct compression or granulation and are evaluated for quality parameters including hardness, friability, weight variation, drug content, dissolution, layer adhesion, and stability according to ICH guidelines.

Despite their advantages, bilayer tablets face challenges such as poor interlayer adhesion, drug incompatibility, inconsistent drug-release profiles, and difficulties in large-scale manufacturing. Future research is expected to focus on Quality by Design (QbD), advanced polymers, nanotechnology-based drug delivery systems, and personalized dosage forms to improve manufacturing efficiency, product quality, and therapeutic outcomes for HIV patients.

Conclusion

Triple-combination bilayer antiretroviral tablets offer an innovative and effective pharmaceutical approach for HIV management by integrating multiple drugs into a single dosage form. This technology has the potential to reduce pill burden, improve patient adherence, enhance treatment convenience, and optimize long-term therapeutic outcomes. Continued advancements in formulation strategies and manufacturing technologies are expected to further strengthen the clinical utility of bilayer tablet systems in antiretroviral therapy.

References

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Copyright

Copyright © 2026 Ms. Gaikwad Akanksha Shivaji, Dr. M Srinivas, Ms. Vaijayanti Kakade, Ms. Priyanka N. Shinde. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.