Colon-specific double-compression coated pulsatile tablets of ketorolac tromethamine: Formulation development and pharmacokinetics

摘要

In the recent pharmaceutical research, pulsatile drug delivery has been of interest to achieve improved drug therapies. The present study is aimed to formulate and study the pharmacokinetics of colon-specific pulsatile ketorolac tromethamine tablets using double-compression coating method. In this, inner compression coat made of sodium starch glycolate as swelling layer and outer compression coat (release controlling layer) contains sodium alginate and hydroxypropyl methylcellulose K 15M. From the in vitro drug release studies, F5 tablets showed 5.02 ± 0.16% drug release in 5 h and it was progressively expanded to 99.78 ± 0.64% in 24 h that demonstrate the colon-specific drug release. From the stability studies, F5 formulation showed the good stability and it was proved by calculating the similarity factor i.e., 83.92. From the pharmacokinetic evaluation, immediate release core tablets producing peak plasma concentration (Cmax) was 4425.23 ng/ml at 2 h Tmax and colon-specific double-compression coated tablets demonstrated Cmax = 3456.47 ng/ml at 10 h Tmax. The area under curve values for the core and double-compression coated tablets were 10128.53 and 17467.62 ng-h/ml respectively and the mean resident time was 4.21 h and 10.34 h respectively. In conclusion, development of ketorolac tromethamine double-compression coated pulsatile tablets is a promising way to achieve colon-specificity.