title: 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 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.
  
  
  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 Cmaxand AUC0-12 hvalues 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.
  
  
  CONCLUSIONS
  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.
authors: a Department of Pharmacology , Vaagdevi Institute of Pharma Sciences , Warangal , Andhra Pradesh , India.
authors: Gurunath
authors: G
authors: Surampalli
authors: b Faculty of Pharmacy, Department of Pharmaceutics , Omer Al-Mukhtar University , Tobruk , Libya.
authors: Basavaraj K
authors: BK
authors: Nanjwade
authors: c Department of Pharmacology , International Medical Programme, USM-KLE , Belgaum , Karnataka , India , and.
authors: P A
authors: PA
authors: Patil
authors: d Department of Pharmaceutics , Vaagdevi Institute of Pharma Sciences , Warangal , Andhra Pradesh , India.
authors: Rakesh
authors: R
authors: Chilla
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000737:chemistry*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000737:chemistry; D044950:Flavanones / Q000737:chemistry; D006244:Hardness; D008297:Male; D011817:Rabbits; D012995:Solubility; D013607:Tablets / Q000008:administration & dosage* / Q000737:chemistry*; D013777:Tetrazoles / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005079:Excipients; D044950:Flavanones; D013607:Tablets; D013777:Tetrazoles; C005274:naringin; C077793:candesartan cilexetil
keywords: Candesartan; direct compression; naringin; oral bioavailability