Design of hydrogels of 5-hydroxymethyl tolterodine and their studies on pharmacokinetics, pharmacodynamics and transdermal mechanism.
Eur J Pharm Sci
; 96: 530-541, 2017 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-27789373
ABSTRACT
development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin permeation. Finally, Carbopol 940 was selected as the gel matrix with N-methyl pyrrolidone (NMP) chosen as the enhancer. The relationship between time and the steady accumulative percutaneous amount (Q, µgcm-2) of optimized 5-HMT hydrogels was Q4-12h=1290.8t1/2-1227.7. The absolute bioavailability of 5-HMT hydrogels was 20.7% showed in pharmacokinetic study. No skin irritation was observed in 5-HMT hydrogels skin irritation study. In the pharmacodynamic study, the overactive bladder model was induced by 150µg/kg of pilocarpine in rats. The significant effects of 5-HMT hydrogels on the inhibition of urine output on rat model were last to 12h. The optimized 5-HMT hydrogels displayed prolonged pharmacological responses. 5-HMT hydrogels effectively avoided the metabolism difference of enzyme in bodies compared with tolterodine tablets, provided one single active compound in plasma to reduce the variability of having two active compounds. To further elucidate the transdermal mechanism, fourier transform infrared (FTIR) spectroscopy, differential scanning calorimeter (DSC) and activation energy measurements were used to study the transdermal routes and changes of stratum corneum during drug release.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Absorção Cutânea
/
Compostos Benzidrílicos
/
Desenho de Fármacos
/
Hidrogéis
/
Cresóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharm Sci
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China