Characterization and pharmacokinetic study of itraconazole solid dispersions prepared by solvent-controlled precipitation and spray-dry methods.
J Pharm Pharmacol
; 69(12): 1707-1715, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28872678
ABSTRACT
OBJECTIVES:
Solid dispersion formulations have attracted attention to improve solubility and bioavailability of water-insoluble drugs. In this study, the variation of solubility and bioavailability by different preparation methods were studied using itraconazole (ITZ) solid dispersions.METHODS:
Itraconazole solid dispersions were prepared by a solvent-controlled precipitation method (SCPM) using HPMCAS-LF, HCl antisolvent or a spray-drying method (SDM) for comparison. Dissolution tests by pH transition and pharmacokinetic study using male Sprague Dawley rats were conducted. KEYFINDINGS:
Itraconazole solid dispersion dissolution tests by pH transition exhibited better dissolution compared to naive ITZ, limited dissolution in acidic conditions and a burst release at neutral pH. The ITZ solid dispersions by SCPM indicated a smaller-sized particle dispersion, limited dissolution at acidic pH and a higher release at neutral pH compared to those by SDM, suggesting that the increased protonation of anionic polymers and HPMCAS-LF by acidic antisolvent could form a tighter hydrophobic aggregation with ITZ in solid dispersions. ITZ solid dispersion prepared by SCPM also showed improved ITZ absorption in male Sprague Dawley rats compared to SDM and naïve ITZ.CONCLUSIONS:
This study suggests that the SCPM method can be widely used for solid dispersion preparations due to improved dissolution and PK profile.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Solventes
/
Química Farmacêutica
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Itraconazol
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Antifúngicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article