Development and bioavailability assessment of ramipril nanoemulsion formulation

被引:571
作者
Shafiq, Sheikh [1 ]
Shakeel, Faiyaz [1 ]
Talegaonkar, Sushma [1 ]
Ahmad, Farhan J. [1 ]
Khar, Roop K. [1 ]
Ali, Mushir [1 ]
机构
[1] Jamia Hamdard, Dept Pharmaceut, Fac Pharm, New Delhi 110062, India
关键词
nanoemulsion; ramipril; bioavailability; SNEDDS; phase diagrams; solubility; Sefsol; 218;
D O I
10.1016/j.ejpb.2006.10.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of our investigation was to design a thermodynamically stable and dilutable nanoemulsion formulation of Ramipril, with minimum surfactant concentration that could improve its solubility, stability and oral bioavai lability. Formulations were taken from the o/w nanoemulsion region of phase diagrams, which were subjected to thermodynamic stability and dispersibility tests. The composition of optimized formulation was Sefsol 218 (20% w/w), Tween 80 (18% w/w), Carbitol (18% w/w) and standard buffer solution pH 5 (44% w/w) as oil, surfactant, cosurfactant and aqueous phase, respectively, containing 5 mg of ramipril showing drug release (95%), droplet size (80.9 nm), polydispersity (0.271), viscosity (10.68 cP), and infinite dilution capability. In vitro drug release of the nanoemulsion formulations was highly significant (p < 0.01) as compared to marketed capsule formulation and drug suspension. The relative bioavailability of ramipril nanoemulsion to that of conventional capsule form was found to be 229.62% whereas to that of drug suspension was 539.49%. The present study revealed that ramipril nanoemulsion could be used as a liquid formulation for pediatric and geriatric patients and can be formulated as self-nanoemulsifying drug delivery system (SNEDDS) as a unit dosage form. (C) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:227 / 243
页数:17
相关论文
共 47 条
[1]   A THEORETICAL BASIS FOR A BIOPHARMACEUTIC DRUG CLASSIFICATION - THE CORRELATION OF IN-VITRO DRUG PRODUCT DISSOLUTION AND IN-VIVO BIOAVAILABILITY [J].
AMIDON, GL ;
LENNERNAS, H ;
SHAH, VP ;
CRISON, JR .
PHARMACEUTICAL RESEARCH, 1995, 12 (03) :413-420
[2]   A STUDY ON FACTORS INFLUENCING THE DROPLET SIZE IN NONIONIC OIL-IN-WATER MICROEMULSIONS [J].
ATTWOOD, D ;
MALLON, C ;
KTISTIS, G ;
TAYLOR, CJ .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1992, 88 (1-3) :417-422
[4]  
AUNGST BJ, 1994, GATTEFOSSE, V87, P49
[5]   A stability-indicating LC method for the simultaneous determination of ramipril and hydrochlorothiazide in dosage forms [J].
Belal, F ;
Al-Zaagi, IA ;
Gadkariem, EA ;
Abounassif, MA .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2001, 24 (03) :335-342
[6]   Nano-emulsion formulation using spontaneous emulsification:: solvent, oil and surfactant optimisation [J].
Bouchemal, K ;
Briançon, S ;
Perrier, E ;
Fessi, H .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2004, 280 (1-2) :241-251
[7]  
Burcham DL, 1997, BIOPHARM DRUG DISPOS, V18, P737, DOI 10.1002/(SICI)1099-081X(199711)18:8<737::AID-BDD59>3.0.CO
[8]  
2-9
[9]   SELF-EMULSIFYING DRUG DELIVERY SYSTEMS - FORMULATION AND BIOPHARMACEUTIC EVALUATION OF AN INVESTIGATIONAL LIPOPHILIC COMPOUND [J].
CHARMAN, SA ;
CHARMAN, WN ;
ROGGE, MC ;
WILSON, TD ;
DUTKO, FJ ;
POUTON, CW .
PHARMACEUTICAL RESEARCH, 1992, 9 (01) :87-93
[10]   LIPID MICROEMULSIONS FOR IMPROVING DRUG DISSOLUTION AND ORAL ABSORPTION - PHYSICAL AND BIOPHARMACEUTICAL ASPECTS [J].
CONSTANTINIDES, PP .
PHARMACEUTICAL RESEARCH, 1995, 12 (11) :1561-1572