Formulation, Development and Scale-Up of Fixed-Dose Combination Tablets Containing Zidovudine, Lamivudine and Nevirapine

Abstract

Background: The development of antiretroviral associations in a single dosage form aims to ensure improved efficacy, low costs and better adherence to treatment.

Objective: This work performed the pharmacotechnical development, coating, and stability studies of fixed-dose combination tablets of zidovudine, lamivudine and nevirapine (300 + 200 + 150 mg, respectively).

Methods: Qualitative and quantitative planning of diluents (101 and 250 microcrystalline cellulose, spray-dried monohydrate lactose and corn starch) and coating polymers (Opadry white II HP® and Instacoat Aqua Moistshield II®) were analyzed, and direct compression (DC) and wet granulation (WG) methods were tested aiming the development of the pharmaceutical form. Quality control was carried out according to the specifications set by official compendia. The chosen formulation was scaled-up and the industrial batches were submitted to accelerated and long-term stability studies.

Results: The batches obtained by WG met the requirements, using 101 microcrystalline cellulose, corn starch and Opadry white II HP® as excipients. The DC trial was not possible due to the need of a greater ratio of excipients to improve formulation properties.

Conclusion: Thus, this study brings a new therapeutic alternative for HIV treatment, contributing to the development of another possibility to simplify drug administration.

Keywords: AIDS; Drug stability; HIV; coating polymers; highly active antiretroviral therapy; tablet..