Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation

Abstract

Objective: The aim of this study was to develop a novel tablet formulation of amorphous candesartan cilexetil (CAN) solid dispersion involving effective P-gp inhibition for optimal drug delivery by direct compression (DC) method. Methods: To accomplish DC, formulation blends were evaluated for micromeritic properties. The Carr index, Hausner ratio, flow rate and cotangent of the angle a were determined. The tablets with and without naringin prepared by DC technique were evaluated for average weight, hardness, disintegration time and friability assessments. The drug release profiles were determined to study the dissolution kinetics. In vivo pharmacokinetic studies were conducted in rabbits. Accelerated stability studies were performed for tablets at 40 ± 2 C/75% RH ± 5% for 6 months. Results: FTIR studies confirmed no discoloration, liquefaction and physical interaction between naringin and drug. The results indicated that tablets prepared from naringin presented a dramatic release (82%) in 30 min with a similarity factor (76.18), which is most likely due to the amorphous nature of drug and the higher micromeritic properties of blends. Our findings noticed 1.7-fold increase in oral bioavailability of tablet prepared from naringin with mean C max and AUC 0-12 h values as 35.81 ± 0.13 mg/mL and 0.14 ± 0.09 mg h/mL, respectively. The tablets with and without naringin prepared by DC technique were physically and chemically stable under accelerated stability conditions upon storage for 6 months. Conclusion: These results are attractive for further development of an oral tablet formulation of CAN through P-gp inhibition using naringin, a natural flavonoid as a pharmaceutical excipient.

Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

“…Finally, the mixture was compressed into convex faced tablets weighing 200 mg, with 5 mm diameter by a single punch tablet machine. The compression force and time was 20 kN and 32 s, respectively (Surampalli & Nanjwade, 2014).…”

Asam Arsenat (H3AsO4) : Analisis Molekular dan Karakteristik Senyawa

“…Optimasi MM2 Minimization (121)(122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135) 2. Optimasi MM2 Dynamics (136)(137)(138)(139)(140) 3. Optimasi MM2 Properties (30; [141][142][143][144][145]…”

Candesartan Cilexetil In Vitro–In Vivo Correlation: Predictive Dissolution as a Development Tool

“…Candesartan cilexetil low solubility, combined with its efflux transport by the intestinal P-glycoprotein and its vulnerability to enzymatic degradation in small intestine contribute to the observed low oral bioavailability [7][8][9]. Recently, an improvement of candesartan cilexetil oral bioavailability in rabbits has been demonstrated by using naringin as a P-gp inhibitor [10]. After absorption, candesartan is mainly excreted unchanged in urine and feces (by biliary excretion).…”