Transformation of acidic poorly water soluble drugs into ionic liquids.
Eur J Pharm Biopharm
; 94: 73-82, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25976317
ABSTRACT
Poor water solubility of active pharmaceutical ingredients (API) is a major challenge in drug development impairing bioavailability and therapeutic benefit. This study is addressing the possibility to tailor pharmaceutical and physical properties of APIs by transforming these into tetrabutylphosphonium (TBP) salts, including the generation of ionic liquids (IL). Therefore, poorly water soluble acidic APIs (Diclofenac, Ibuprofen, Ketoprofen, Naproxen, Sulfadiazine, Sulfamethoxazole, and Tolbutamide) were converted into TBP ILs or low melting salts and compared to the corresponding sodium salts. Free acids and TBP salts were characterized by NMR and IR spectroscopy, DSC and XRPD, DVS and dissolution rate measurements, release profiles, and saturation concentration measurements. TBP salts had lower melting points and glass transition temperatures and dissolution rates were improved up to a factor of 1000 as compared to the corresponding free acid. An increase in dissolution rates was at the expense of increased hygroscopicity. In conclusion, the creation of TBP ionic liquids or solid salts from APIs is a valuable concept addressing dissolution and solubility challenges of poorly water soluble acidic compounds. The data suggested that tailor-made counterions may substantially expand the formulation scientist's armamentarium to meet challenges of poorly water soluble drugs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Preparações Farmacêuticas
/
Água
Idioma:
En
Revista:
Eur J Pharm Biopharm
Assunto da revista:
FARMACIA
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FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha