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

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. To accomplish DC, formulation blends were evaluated for micromeritic properties....

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Bibliographic Details
Published in:	Drug delivery Vol. 23; no. 7; p. 2124
Main Authors:	Surampalli, Gurunath, Nanjwade, Basavaraj K, Patil, P A, Chilla, Rakesh
Format:	Journal Article
Language:	English
Published:	England 01-09-2016
Subjects:	Animals ATP Binding Cassette Transporter, Sub-Family B - antagonists & inhibitors Benzimidazoles - administration & dosage Benzimidazoles - chemistry Biological Availability Biphenyl Compounds - administration & dosage Biphenyl Compounds - chemistry Chemistry, Pharmaceutical - methods Drug Delivery Systems - methods Excipients - chemistry Flavanones - chemistry Hardness Male Rabbits Solubility Tablets - administration & dosage Tablets - chemistry Tetrazoles - administration & dosage Tetrazoles - chemistry naringin oral bioavailability Candesartan direct compression
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Summary:	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. To accomplish DC, formulation blends were evaluated for micromeritic properties. The Carr index, Hausner ratio, flow rate and cotangent of the angle α 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. 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 and AUC values as 35.81 ± 0.13 μg/mL and 0.14 ± 0.09 μg 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. 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.
ISSN:	1521-0464
DOI:	10.3109/10717544.2014.945017