A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets

Abstract

Abstract. A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on timecontrolled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drugrelease studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42±0.12% in 5 h) and progressively released to the colon (99.78±0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max ) was 14,677.51±12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max =12,374.67± 16.72 ng/ml at 12 h T max . The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Solid dispersion-based pellet for colon delivery of tacrolimus through time- and pH-dependent layer coating: preparation, in vitro and in vivo studies

“…To generate in vitro-in vivo correlation (IVIVC), the in vitro cumulative percent of tacrolimus release of optimized CSP formulation was compared against the extent of in vivo absorption, i.e., cumulative AUC values of the same formulation (Vemula, 2015c).…”

Development and In vitro-In vivo Characterization of Chronomodulated Multi-Particulate Drug Delivery System of Terbutaline Sulphate for Treatment of Nocturnal Asthma by box–Behnken Statistical Design

“…To test the significance of difference between calculated pharmacokinetic parameters of both immediate-release tablet and formulation MP1 statistical analysis using analysis of variance (ANOVA) was done and a P value of P<0.05 was considered statistically significant (Vemula, 2015).…”

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites

“…8 Similarly, Tung et al investigated colon-specific targeted tablets of metronidazole through a pectin/hydroxypropyl methylcellulose dry powder coating. 9 Vemula also reported double-compression-coated mini-tablets for pulsatile colonic release of flurbiprofen, 10 as well as colon-specific pH-and time-dependent tablets. 11 However, only a few studies have reported about colonspecific pulsatile nanodrug delivery systems using advanced technologies.…”

“…7 Many efforts have been dedicated to drug colon-targeted pulsatile release through traditional methods on solid dosage forms. [8][9][10][11] Vemula and Katkum reported coated tablets of ketorolac tromethamine, which were prepared using double-compression coating method. 8 Similarly, Tung et al investigated colon-specific targeted tablets of metronidazole through a pectin/hydroxypropyl methylcellulose dry powder coating.…”