Manipulating hydrate formation during high shear wet granulation using polymeric excipients.
J Pharm Sci
; 98(12): 4670-83, 2009 Dec.
Article
en En
| MEDLINE
| ID: mdl-19455624
Active pharmaceutical ingredients (API) can undergo an anhydrate to hydrate transformation during wet granulation and this transformation may either result in mixed crystalline forms or an unwanted form in the final drug product. Previous studies have shown that it may be possible to inhibit this transformation with polymeric excipients. In this study, three model compounds, caffeine (CAF), carbamazepine (CBZ), and sulfaguanidine (SGN), were subjected to high shear wet granulation and phase transformations were monitored using in-line Raman spectroscopy. Wet granulation was performed in the presence and absence of various polymeric excipients to determine the extent of the inhibitory effects. Although several polymers had some retardation effect, cross-linked poly(acrylic) acid was found to completely inhibit the CAF transformation and both hydroxypropyl methylcellulose and cross-linked poly(acrylic) acid completely inhibited the CBZ transformation. For SGN, transformation to the hydrate was rapid, even in the presence of the polymers. The observed inhibitory effects were attributed to either specific interactions between the polymer and the API crystal or substantial water absorption by the polymer. There was also evidence from physical property testing that the inclusion of a small amount of inhibitory polymer did not significantly change the compaction or flow behavior of the final granulation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Composición de Medicamentos
/
Excipientes
Idioma:
En
Revista:
J Pharm Sci
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos