Formulation of risperidone in floating microparticles to alleviate its extrapyramidal side effects

• Main Authors: Hussein O. Ammar, Mahmoud M. Ghorab, Azza A. Mahmoud, Shereen H. Noshi
• Format: Article
• Language: English
• Published: SpringerOpen 2016-12-01
• Series: Future Journal of Pharmaceutical Sciences
• Subjects: Gastroretentive drug delivery system; Eudragit S100; Compritol 888 ATO; Cyclodextrin; Pharmacokinetics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2314724516300346

Risperidone 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 (MβCD) and hydroxypropyl-betacyclodextrin (HPβCD), 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 Cmax, longer Tmax and higher AUC values for the optimized formula compared to the marketed oral product (Risperidal® 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.