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Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect.
Drug Dev Ind Pharm. 2018 Jun; 44(6):969-981.DD

Abstract

The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10, and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation. The prepared formulations were further characterized by the droplet size, self-microemulsifying time, zeta potential, polydispersity index (PDI), and robustness to dilution. The in vitro release profile of cinacalcet-SMEDDS was determined in four different release medium and in fasted state and fed state of simulated gastrointestinal fluid. Cinaclcet-SMEDDS were implemented under fed and fasted state in dogs and product REGPARA® was used as a comparison to the prepared formulation in the pharmacokinetics. The result showed the components of SMEDDS, the amount of oil, the ratio of surfactant, and co-surfactant was optimized using solubility, pseudo-ternary phase diagram studies, and response surface methodology. In vitro drug release studies indicated that the cinacalcet-SMEDDS eliminated the effect of pH variability in release medium and variational gastroenteric environments with improved drug release performance. Pharmacokinetic studies revealed that the profiles of cinacalcet-SMEDDS were similar both in the fasted and fed state compared with commercial product, indicating the formulation significantly promoted the absorption, enhanced bioavailability and had no food effect essentially. It is concluded that poorly water-soluble drug cinacalcet was improved in the solubility and bioavailability by using a successful oral dosage form the SMEDDS, and eliminated food effect as well.

Authors+Show Affiliations

a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.a School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29313395

Citation

Cao, Mengyuan, et al. "Formulation Optimization and Pharmacokinetics Evaluation of Oral Self-microemulsifying Drug Delivery System for Poorly Water Soluble Drug Cinacalcet and No Food Effect." Drug Development and Industrial Pharmacy, vol. 44, no. 6, 2018, pp. 969-981.
Cao M, Xue X, Pei X, et al. Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect. Drug Dev Ind Pharm. 2018;44(6):969-981.
Cao, M., Xue, X., Pei, X., Qian, Y., Liu, L., Ren, L., & Chen, G. (2018). Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect. Drug Development and Industrial Pharmacy, 44(6), 969-981. https://doi.org/10.1080/03639045.2018.1425428
Cao M, et al. Formulation Optimization and Pharmacokinetics Evaluation of Oral Self-microemulsifying Drug Delivery System for Poorly Water Soluble Drug Cinacalcet and No Food Effect. Drug Dev Ind Pharm. 2018;44(6):969-981. PubMed PMID: 29313395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Formulation optimization and pharmacokinetics evaluation of oral self-microemulsifying drug delivery system for poorly water soluble drug cinacalcet and no food effect. AU - Cao,Mengyuan, AU - Xue,Xu, AU - Pei,Xixi, AU - Qian,Yiwen, AU - Liu,Lan, AU - Ren,Lili, AU - Chen,Guoguang, Y1 - 2018/01/25/ PY - 2018/1/10/pubmed PY - 2018/9/25/medline PY - 2018/1/10/entrez KW - Cinacalcet KW - SMEDDS KW - central composite design KW - fasted KW - food effect KW - response surface method SP - 969 EP - 981 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 44 IS - 6 N2 - The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10, and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation. The prepared formulations were further characterized by the droplet size, self-microemulsifying time, zeta potential, polydispersity index (PDI), and robustness to dilution. The in vitro release profile of cinacalcet-SMEDDS was determined in four different release medium and in fasted state and fed state of simulated gastrointestinal fluid. Cinaclcet-SMEDDS were implemented under fed and fasted state in dogs and product REGPARA® was used as a comparison to the prepared formulation in the pharmacokinetics. The result showed the components of SMEDDS, the amount of oil, the ratio of surfactant, and co-surfactant was optimized using solubility, pseudo-ternary phase diagram studies, and response surface methodology. In vitro drug release studies indicated that the cinacalcet-SMEDDS eliminated the effect of pH variability in release medium and variational gastroenteric environments with improved drug release performance. Pharmacokinetic studies revealed that the profiles of cinacalcet-SMEDDS were similar both in the fasted and fed state compared with commercial product, indicating the formulation significantly promoted the absorption, enhanced bioavailability and had no food effect essentially. It is concluded that poorly water-soluble drug cinacalcet was improved in the solubility and bioavailability by using a successful oral dosage form the SMEDDS, and eliminated food effect as well. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/29313395/Formulation_optimization_and_pharmacokinetics_evaluation_of_oral_self_microemulsifying_drug_delivery_system_for_poorly_water_soluble_drug_cinacalcet_and_no_food_effect_ L2 - https://www.tandfonline.com/doi/full/10.1080/03639045.2018.1425428 DB - PRIME DP - Unbound Medicine ER -