The aim of present study was to develop an optimized gastric floating controlled drug delivery system of Clarithromycin (CLA). The Clarithromycin is poorly water soluble drug and gastric irritant. To overcome these problems attempt was made in present study to form inclusion complex of Clarithromycin with Nanosponges. β-Cyclodextrin (CD) based Nanosponges (NS) are novel class of cross-linked derivatives of Cyclodextrin. The Nanosponges were synthesized by carbonylation of β-Cyclodextrin to exploit its porous structure for drug entrapment. A better alternative to β-CD is it’s Nanosponges due to low solubility & toxicity of β-CD. The final Nanosponges structure contains both lipophilic cavities of CD and carbonate bridges leading to a network of more hydrophilic channels. NS are solid, insoluble in water, crystalline in nature and thermally stable compounds. They have been used to increase the solubility of poorly water soluble actives, to avoid gastric irritation and control the release of drug. Present study aimed at formulating complex of CLA with NS by solid dispersion technique and absence of interaction of CLA with NS was confirmed by XRPD, DSC and FTIR studies. The result of XRPD results showed that the crystallinity of CLA was decreased after loading into NS. The 32 full factorial experimental designs were applied for tablet formulation. The in vitro dissolution studies indicated a slow and prolonged release of drug over the period of 12 h. Histopathological study revealed non irritancy of drug-NS complex to gastric mucosa (of rat). Hence drug-NS complex found to be suitable for designing into unit dosage forms. The release study of drug from tablet as well as capsule as unit dosage forms indicated controlled release of a drug when compared with marketed preparation.