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Titolo:
Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray
Autore:
Loftsson, T; Guomundsdottir, H; Sigurjonsdottir, JF; Sigurosson, HH; Sigfusson, SD; Masson, M; Stefansson, E;
Indirizzi:
Univ Iceland, Fac Pharm, IS-127 Reykjavik, Iceland Univ Iceland Reykjavik Iceland IS-127 c Pharm, IS-127 Reykjavik, Iceland Univ Iceland, Dept Ophthalmol, Landspitali, IS-101 Reykjavik, Iceland UnivIceland Reykjavik Iceland IS-101 spitali, IS-101 Reykjavik, Iceland
Titolo Testata:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
fascicolo: 1, volume: 212, anno: 2001,
pagine: 29 - 40
SICI:
0378-5173(20010105)212:1<29:CSOBFO>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
WATER-SOLUBLE POLYMERS; 1,4-BENZODIAZEPINE DRUGS; ACIDIC MEDIA; KINETICS; HYDROLYSIS; DIAZEPAM; PHARMACOKINETICS; COMPLEXATION; MECHANISMS; EQUILIBRIUM;
Keywords:
solubility; benzodiazepines; cyclodextrin; complexation; ionization;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Loftsson, T Univ Iceland, Fac Pharm, POB 7210, IS-127 Reykjavik, Iceland Univ Iceland POB 7210 Reykjavik Iceland IS-127 javik, Iceland
Citazione:
T. Loftsson et al., "Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray", INT J PHARM, 212(1), 2001, pp. 29-40

Abstract

The cyclodextrin solubilization of three benzodiazepines, i.e. alprazolam,midazolam and triazolam, was investigated. The cyclodextrin solubilizationwas enhanced through ring-opening of the benzodiazepine rings and ionization of the ring-open forms. Additional enhancement was obtained through interaction of a water-soluble polymer with the cyclodextrin complexes. The ring-opening was pH-dependent and completely reversible, the ring-open forms dominating at low pH but the ring-closed forms at physiologic pH. The ring-closed forms were rapidly regenerated upon elevation of pH. In freshly collected human serum in vitro at 37 degreesC, the half-life for the first-orderrate constant for the ring-closing reaction was estimated to be less than 2 min for both alprazolam and midazolam. Midazolam (17 mg/ml) was solubilized in aqueous pH 4.3 nasal formulation containing 14% (w/v) sulfobutyletherbeta -cydodextrin, 0.1% (w/v) hydroxypropyl methylcellulose, preservativesand buffer salts. Six healthy volunteers received 0.06 mg/kg midazolam intranasally and 2 mg intravenously, and blood samples were collected up to 360 min after the administration. Midazolam was absorbed rapidly reaching maximum serum concentrations of 54.3 +/- 5.0 ng/ml at 15 +/- 2 min. The elimination half-life of midazolam was 2.2 +/- 0.3 h and the absolute availability was 73 +/- 7%. All mean values +/- SEM. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 11:58:04