Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability <1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0–∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.

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Abstract In the current study, surface-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of brigatinib (BRB) were prepared by studying the variables PLGA (polymer), PVA (stabilizer) and chitosan (coater) against experimentally obtained responses. The optimized NPs (F2) were evaluated in vitro for differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size, polydispersity index (PDI) and drug entrapment (EE), in vitro release, hematocompatibility and in vitro anticancer studies. The optimized NPs’ (F2) composition, PLGA (75 mg), PVA (0.55% w/v), chitosan (0.75% w/v) and 30 mg of BRB was found to be optimum with particle size (406.3 ± 5.1 nm), PDI (0.277), ζ potential (30.4 ± 3.3 mV) and %EE (82.32%). The in vitro release profile showed a sustained release pattern of the F2 nanoparticles of BRB. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed a significant anticancer activity for F2 NPs against A549 cell lines in comparison to free BRB. The result obtained in this work indicated the immense potential of nanoparticles to effectively deliver the BRB to the cancer site for the treatment of non-small cell lung cancer.