Development of Room Temperature Stable Formulation of Formoterol Fumarate/Beclomethasone HFA pMDI

Various solubilizers were tried during preformulation study. Propylene glycol and Transcutol were selected as solubilizers for further study. Poloxamer 407 gives gelation temperature in nasal temperature range 280 to 350 in 18% w/v concentration. Addition of bioadhesive polymer from 0.2% to 0.7% further lowered the gelation temperature from 340 to 290. Gelation temperatures obtained using two different methods (visual inspection and rheological method) did not vary more than ±10. The gelation temperature lowering effect of bioadhesive polymer might have caused in part by the increased viscosity after dissolution of mucosadhesive polymer. The pH values of all formulations were found in the range of 5.3 to 5.6. Formulation should posses’ mild acidic pH for activation of lysozyme (A natural antibacterial enzyme important for controlling nasal microbial count which becomes inactive at alkaline pH). The pKa of ondansetron hydrochloride is 7.4; so drug present in solubilised form in pH range 5 to 6.5 (ondansetron hydrochloride precipitate above 6.8). It was observed that the concentration of bioadhesive polymer increased from 0.2% to 0.7% showed retardation of ondansetron hydrochloride release, probable mechanism for such retardation of release may be reduction in number and dimensions of the channels in gel structure by increased viscosity of the formulation. From the study it can be concluded that the nasal in situ gels can be formulated of ondansetron hydrochloride using PF127 and bioadhesive polymer.