Hydroxypropyl β-Cyclodextrin (HBC) Multicomponent Complexation and pH independent controlled release delivery system to Improved Dissolution and oral Bioavailability of Ondansetron HCI

  The objective of this study was to develop pH independent controlled release matrix tablets of Ondansetron HCl by using Multi component Complexation technique, Methocel K100M as release retarding materials and HP β-cyclodextrin was selected as release modulators. Ondansetron is weakly basic drug and their salts shows pH-dependent solubility that may show drug release problems at higher pH of small intestine. Incorporation of weakly basic drugs, exhibiting pH dependent solubility, into oral controlled release delivery systems shows pH dependent release profiles. In the present investigation, an attempt was made to pH-solubility dependence of drug and dissolution enhancement was attained by inclusion complex of Ondansetron with HP- β-cyclodextrin at 1:1 (drug: β-CD) molar ratio and then prepared complex hydroxyl propyl methyl cellulose controlled released matrix tablets. The in vitro drug release studies were carried out in pH1.2 buffer for 2 hrs and then in pH 6.8 phosphate buffer up to 24 hrs. The formulated matrix tablet F4 (without complexation) was very slow and drug is not released completely from matrix tablets in 6.8 pH phosphate buffer. The matrix tablets prepared using HP β- cyclodextrin with PVP (F8) showed a superior dissolution rate and good dissolution profile that was comparable to without complexation of Ondansetron HCl. Dissolution results showed pH independent controlled and almost complete release behavior of Ondansetron HCl up to 24 hrs time period. The drug release mechanism of the HPMC matrix tablets was found to be quasi Fickian mechanism. These results suggested that the oral bioavailability of Ondansetron HCl was significantly improved by Multi component Complexation strategies.