Formulation development and optimization of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg FDC tablets by D-optimal mixture design

Abstract

The usage of fixed dose combination (FDC) tablets of Lamivudine and Tenofovir Disoproxil Fumarate (TDF) is increasing due to increased incidences of HIV/Hepatitis B and HIV/TB co-infections. This is likely to increase the financial crisis due to limited resources for funding procurement of ready-made products from the pharmaceuticals manufacturing leading countries. Therefore, production of local oral tablets containing Lamivudine and TDF FDC is inevitable. Lamivudine 300 mg/TDF 300 mg tablets were developed and optimized by D-optimal mixture design and produced by direct compression technique. Twenty trial formulations with independent variables, including PVP-CL 1–12.00%, PVP-K30 1–10.00%, starch-1500 2.5–12.5% and Avicel-PH102 2–19.25% were prepared by direct compression technique. The formulations were assessed on assay, dissolution, friability, weight variation and disintegration time. It was found that assay ranged from 98.13–101.95% for Lamivudine, 98.25–102.84 for TDF, both were within the in-house assay specification of 95 to 105%. Dissolution at single point was above 80% for Lamivudine 93.96–100.55% and 95.85–103.15% for TDF, disintegration time was between 1.92–66.33 min and friability 0.06–12.56%. Out of twenty formulation trials, eight formulations had all parameters in proven acceptable range. On optimization, one formulation with independent variables, PVP-CL 5.67%, PVP-K30 1.00%, Starch-1500 5.76% was selected. The optimized formulation was comparable to the reference product on the market with similarity factor (f2) and difference factor (f1) within the acceptable range for both Lamivudine and TDF.

Study on Cause-Effect Relations and Optimization of Tablets Containing Aquilaria Crassna Spray-Dried Extract

“…DCPA is a nonhygroscopic filler and absorbed less than 1 % water [17], therefore, when % DCPA in filler (X1) increased, the water penetration into the tablet may be slowed down and hence, the disintegration process was prolonged. This was in line with the rule reported previously by Tibalinda P [18].…”

Development of a Solid Formulation Containing a Microemulsion of a Novel Artemisia Extract with Nematocidal Activity for Oral Administration

“…Response surface methodologies, such as mixture designs, have recently been used in the formulation of microemulsions (ME) [ 25 , 26 , 27 ], self-emulsifying drug delivery systems (SEDDS) [ 28 , 29 , 30 ], liposomes [ 31 , 32 ] and tablets [ 19 , 33 , 34 , 35 , 36 , 37 , 38 ]. The D-optimal design is one of the most used methodologies in this field, because it allows different composition constraints, in which the sum of all components is constant (100% w / w ).…”

Neurocognitive and Neuroarchitectural Changes in the Prefrontal Cortex of Wistar Rats Treated with Highly Active Antiretroviral Therapy

“…These results, therefore, suggest that both tenofovir and lamivudine can induce an inflammatory cascade in the brain, which drives neurodegeneration as seen in HAND (Rojo et al 2008;Gelders et al 2018). It is possible that in these conditions, reactive astrocytes or microglia may instigate the production of pro-inflammatory proteins associated with the onset of various neurodegenerative diseases (Lu et al 2010;Vivithanaporn et al 2016), including AIDS-induced parkinsonism (Devine et al 2018). Our results agree with findings from a previous investigation that showed that administration of efavirenz increased astrogliosis in mice (Petrov et al 2019).…”