PREPARATION AND IN VITRO EVALUATION OF IN SITU GELLING GASTRORETENTIVE SALBUTAMOL SULFATE LIQUID FORMULATIONS

Salbutamol is a selective β2-adreno-receptor stimulant and is given four times daily in a dose of 2.4 mg orally to maintain therapeutic blood level. It is known to be absorbed in proximal parts of the small intestine. Prolonging gastric residence time is, therefore, beneficial to improve its bioavailability. Hence, seven in situ gelling liquid formulations were prepared using sodium alginate (SA) as gel forming agent and HPMC as viscosity enhancer. CaCO₃ was incorporated as cross-linker and floating agent. Gelling capacity was evaluated based on a graded response which indicates rapidity of gelation and time taken by the gel to dissolve. All the formulations showed instant gelation but with regard to integrity, all formulations except the one with lowest SA level formed stiff gels maintaining integrity for at least 12 hr. With respect to floating behavior, all formulations except the one with the lowest SA level floated for more than 12 hr irrespective of their composition. Most of the formulations took less than 1 min to float but those with the lowest SA and CaCO₃ levels floated after about 2 min. Drug release study revealed release retarding behavior of the formulations and noticeable burst release. This effect was reduced at higher concentration of SA and CaCO₃. Release retarding effect of SA was only marginal at higher concentrations. CaCO₃ showed a similar effect but at higher levels insignificant change in release was observed. The drug release process, in all cases, best fits first order kinetics (R2 ranged between 0.932 and 0.991) and in most cases it seemed to occur by non-Fickian mechanisms (0.43 < n < 0.85). In formulations with lowest levels of SA and CaCO₃, quasi-Fickian diffusion (n < 0.43) process prevailed. The study demonstrated that the in situ gelling formulations can be used as novel formulations with sustained drug release, improved bioavailability and thereby improve patient compliance