Abstract
Objective: This study is to formulate bi-layer tablet as a multidrug regimen against each reference listed drugs of Brand SUSTIVA® (efavirenz tablets 600 mg), EPIVER®(lamivudine tablets 300 mg), and VIREAD®(tenofovir disoproxil tablets 300 mg) to treat human immunodeficiency virus (HIV) infections. Which provides highly active antiretroviral therapy to provide effective treatment. Methods: Bilayer formulation was developed with each blend of layer-I (efavirenz) and layer-II (lamivudine and tenofovir disoproxil fumarate) through wet granulation process and roller compaction process, respectively. Further, both layers were compressed by using bi-layer compression followed by film coating. Layer-I and II formulations were developed by using various concentrations of diluents, surfactants, and disintegrants to improve the solubility of efavirenz and improve the flowability and uniformity of layer-II. Finally, the optimum formulation was developed to compare the in vitro dissolution with each branded formulation. Results: Drug-excipients interaction results revealed that the mixtures of three drug substances in 50 °C/75 % relative humidity (RH) resulted in an increase in tenofovir IMP-E and the highest unknown impurity was significantly increased and additionally decreased tenofovir assay in the presence of efavirenz. Sodium lauryl sulfate is very critical and it acts as a wetting agent and increases the solubility of efavirenz, and directly influences the dissolution of a drug product. Microcrystalline and croscarmellose sodium have a chance to affect the dissolution and friability of tenofovir. Powdered cellulose was acting as a diluent and flow property of the lamivudine part and it also affects the uniformity and dissolution. So, these ranges were optimized. X-ray diffraction (XRD) indicates there are no polymorphic changes for the optimized formulation and there is no interaction between the three active substances, and finally, in vitro dissolution results for the optimized formulation against the reference drugs. Conclusion: Optimum formulation yielded consistent drug release against each branded drug to treat human immunodeficiency virus (HIV1) infections. This formulation is robust and easily scale up for the next stage.
Highlights
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form [1]
The results revealed that the drug release of tenofovir disoproxil fumarate (TDF), lamivudine (LMV) was not sensitive to pH
From the physical evaluation of active substances data, it is evident that the tenofovir disoproxil fumarate (TDF) and lamivudine (LMV) active pharmaceutical ingredients (APIs) have very poor flow properties
Summary
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form [1]. Terms like "combination drug" or "combination drug product" can be common shorthand for a fixeddose combination (FDC) product. Fixed-dose formulations can be administered as a multi-drug regimen to treat various diseases by an effect on different modes of action. They offer convenience, reduced dosing unit burden, and cost savings. The aging population in developed countries will need multiple medications to treat age-related diseases and co-morbidities. The recommended fixed-dose combination (FDC) drugs such as efavirenz, lamivudine, and tenofovir disoproxil fumarate have novel approaches of multiple dosage regimens to treat human immunodeficiency virus (HIV-1) infection through nucleotide reverse transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors
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