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Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation.
Drug Deliv. 2016 Sep; 23(7):2124-2138.DD

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 Cmax and AUC0-12 h 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.

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.

Authors+Show Affiliations

a Department of Pharmacology , Vaagdevi Institute of Pharma Sciences , Warangal , Andhra Pradesh , India.b Faculty of Pharmacy, Department of Pharmaceutics , Omer Al-Mukhtar University , Tobruk , Libya.c Department of Pharmacology , International Medical Programme, USM-KLE , Belgaum , Karnataka , India , and.d Department of Pharmaceutics , Vaagdevi Institute of Pharma Sciences , Warangal , Andhra Pradesh , India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25080228

Citation

Surampalli, Gurunath, et al. "Novel Tablet Formulation of Amorphous Candesartan Cilexetil Solid Dispersions Involving P-gp Inhibition for Optimal Drug Delivery: in Vitro and in Vivo Evaluation." Drug Delivery, vol. 23, no. 7, 2016, pp. 2124-2138.
Surampalli G, Nanjwade BK, Patil PA, et al. Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation. Drug Deliv. 2016;23(7):2124-2138.
Surampalli, G., Nanjwade, B. K., Patil, P. A., & Chilla, R. (2016). Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation. Drug Delivery, 23(7), 2124-2138.
Surampalli G, et al. Novel Tablet Formulation of Amorphous Candesartan Cilexetil Solid Dispersions Involving P-gp Inhibition for Optimal Drug Delivery: in Vitro and in Vivo Evaluation. Drug Deliv. 2016;23(7):2124-2138. PubMed PMID: 25080228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation. AU - Surampalli,Gurunath, AU - Nanjwade,Basavaraj K, AU - Patil,P A, AU - Chilla,Rakesh, Y1 - 2014/07/31/ PY - 2016/10/18/pubmed PY - 2017/3/3/medline PY - 2014/8/1/entrez KW - Candesartan KW - direct compression KW - naringin KW - oral bioavailability SP - 2124 EP - 2138 JF - Drug delivery JO - Drug Deliv VL - 23 IS - 7 N2 - 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 Cmax and AUC0-12 h 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. 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. SN - 1521-0464 UR - https://www.unboundmedicine.com/medline/citation/25080228/Novel_tablet_formulation_of_amorphous_candesartan_cilexetil_solid_dispersions_involving_P_gp_inhibition_for_optimal_drug_delivery:_in_vitro_and_in_vivo_evaluation_ L2 - https://www.tandfonline.com/doi/full/10.3109/10717544.2014.945017 DB - PRIME DP - Unbound Medicine ER -