Noshi, Shereen HMahmoud, Azza AGhorab, Mahmoud MAmmar, Hussein O2019-12-222019-12-222016-122314-7245https://doi.org/10.1016/j.fjps.2016.08.001https://www.sciencedirect.com/science/article/pii/S2314724516300346Accession Number: WOS:000447702600002Risperidone is effective in the treatment of positive as well as negative symptoms of schizophrenia. But, there is a strong correlation between plasma levels of risperidone and its adverse effects. Objective: This study aimed to develop risperidone in floating microparticles to overcome its extrapyramidal side effects. Methods: Floating microparticles were prepared using Eudragit S100, hydroxypropylmethyl cellulose (HPMC), Gelucires (Gelucire 43/01 pellets, Gelucire 44/14 and Gelucire 50/13), Geleol mono and diglyceride NF, glyceryl monostearate, Compritol 888 ATO, methyl-betacyclodextrin (M beta CD) and hydroxypropyl-betacyclodextrin (HP beta CD), by emulsion solvent diffusion technique. In-vitro experiments were conducted to optimize formulation parameters regarding floating ability, yield value, drug loading and in-vitro release properties. The best formula was investigated for its in-vivo floating ability and for its pharmacokinetics as well as its extrapyramidal side effects in human volunteers. Results: The optimized floating microparticles showed promising in-vitro experiment performance with floating ability up to 95.93% for 12 h. Also, this floating ability was confirmed using in-vivo x-ray studies. Pharmacokinetics studies revealed significant (p < 0.05) lower C-max, longer T-max and higher AUC values for the optimized formula compared to the marketed oral product (Risperidal (R) 4 mg tablets) indicating gradually release properties which lead to high treatment efficacy of the drug with obvious reduced extrapyramidal side effects. Conclusion: These results proved that formulating risperidone as floating microparticles is a suitable dosage form for overcoming risperidone side effects. (C) 2016 Production and hosting by Elsevier B.V.en-USPharmacokineticsCyclodextrinCompritol 888 ATOEudragit S100Gastroretentive drug delivery systemArticlehttps://doi.org/10.1016/j.fjps.2016.08.001