Purpose The aim of this study was to develop novel paclitaxel-loaded proliposome tablet formulations for pulmonary drug delivery. Method Proliposome powder formulations (i.e. F1 – F27) were prepared employing Lactose monohydrate (LMH), Microcrystalline cellulose (MCC) or Starch as a carbohydrate carriers and Soya phosphatidylcholine (SPC), Hydrogenated soya phosphatidylcholine (HSPC) or Dimyristoly phosphatidylcholine (DMPC) as a phospholipid. Proliposome powder formulations were prepared in 1:5, 1:15 or 1:25 w/w lipid phase to carrier ratio (lipid phase; comprising of phospholipid and cholesterol in 1:1 M ratio) and Paclitaxel (PTX) was used as model anticancer drug. Results Based on flowability studies, out of 27 formulations; F3, F6, and F9 formulations were selected as they exhibited an excellent angle of repose (AOR) (17.24 ± 0.43, 16.41 ± 0.52 and 15.16 ± 0.72°), comparatively lower size of vesicles (i.e. 5.35 ± 0.76, 6.27 ± 0.59 and 5.43 ± 0.68 μm) and good compressibility index (14.81 ± 0.36, 15.01 ± 0.35 and 14.56 ± 0.14) via Carr’s index. The selected formulations were reduced into Nano (N) vesicles via probe sonication, followed by spray drying (SD) to get a dry powder of these formulations as F3SDN, F6SDN and F9SDN, and gave high yield (>53%) and exhibited poor to very poor compressibility index values via Carr’s Index. Post tablet manufacturing, F3 tablets formulation showed uniform weight uniformity (129.40 ± 3.85 mg), good crushing strength (14.08 ± 1.95 N), precise tablet thickness (2.33 ± 0.51 mm) and a short disintegration time of 14.35 ± 0.56 min, passing all quality control tests in accordance with British Pharmacopeia (BP). Upon nebulization of F3 tablets formulation, Ultrasonic nebulizer showed better nebulization time (8.75 ± 0.86 min) and high output rate (421.06 ± 7.19 mg/min) when compared to Vibrating mesh nebulizer. PTX-loaded F3 tablet formulations were identified as toxic (60% cell viability) to cancer MRC-5 SV2 cell lines while safe to normal MRC-5 cell lines. Conclusion Overall, in this study LMH was identified as a superior carbohydrate carrier for proliposome tablet manufacturing in a 1:25 w/w lipid to carrier ratio for in-vitro nebulization via Ultrasonic nebulizer.