Lamivudine (LVD) is in BCS class II with the issue of minimal oral bioavailability. This issue can be improvised by complexing LVD with polyethylene glycol-4000 (PEG-4000) and Pluronic F-68 (PF-68) by formulation design. The attempt optimized LVD tablets through central composite design (CCD). LVD tablets will be with > 95% dissolution after 30 minitues by employing PEG-4000 and PF-68. Nine LVD tablets were formulated by design and assessed for physicochemical constraints, disintegration time, and drug dissolution. The separate and mutual consequences of PEG-4000 and PF-68 on the disintegration time of LVD tablets are highly significant (P< 0.01). Intermittent levels of PEG-4000 and more levels of PF-68 gave less time for disintegration and a greater amount of drug dissolved at the end of 30 minitues. The study concludes that PF-68 decreases the disintegration time with its concentration and PEG-4000 concentration ingresses the drug release from the formulation. The study also discovered that the optimized LVD tablet with > 97.5% dissolution in 30 minitues could be formulated by employing PEG-4000 at 30 mg and PF-68 at 44.8 mg (F-7).