Improvements of the oral bioavailability of lipophilic drugs can be obtained using lipidic formulations such as the self-emulsifying drug delivery systems. The high shear wet granulation (HSWG), using microemulsions as binder, is a viable process to produce self-emulsifying granules. However only few information are present in the literature on the effect of process variables on the properties of the granules obtained with these binders. Consequently, this article compares the effects of some relevant experimental variables (impeller speed and massing time) on thefinal technological and pharmaceutical properties of the granules produced using simple water, or alternatively, a microemulsion as binder and containing simvastatin (SV) as model drug. The effects of the variables were determined by evaluating the granule median diameter, their particle size distribution, roundness, disintegration time and dissolution rate of SV. Results clearly demonstrated that the microemulsion-based process was less sensitive tooperating conditions than the water-based process. With microemulsion the nucleation process and growth regimes were more difficult to control, resulting in products with broader PSDs. At the same operatingconditions microemulsion-based granules were more brittle but rounder and showed smaller median diameter compared to water-based granules. The dissolution rate of simvastatin was not significantly affected by the operating conditions.

Influence of process variables on the properties of simvastatin self-emulsifying granules obtained through high shear wet granulation

FRANCESCHINIS, ERICA;SANTOMASO, ANDREA CLAUDIO;REALDON, NICOLA
2015

Abstract

Improvements of the oral bioavailability of lipophilic drugs can be obtained using lipidic formulations such as the self-emulsifying drug delivery systems. The high shear wet granulation (HSWG), using microemulsions as binder, is a viable process to produce self-emulsifying granules. However only few information are present in the literature on the effect of process variables on the properties of the granules obtained with these binders. Consequently, this article compares the effects of some relevant experimental variables (impeller speed and massing time) on thefinal technological and pharmaceutical properties of the granules produced using simple water, or alternatively, a microemulsion as binder and containing simvastatin (SV) as model drug. The effects of the variables were determined by evaluating the granule median diameter, their particle size distribution, roundness, disintegration time and dissolution rate of SV. Results clearly demonstrated that the microemulsion-based process was less sensitive tooperating conditions than the water-based process. With microemulsion the nucleation process and growth regimes were more difficult to control, resulting in products with broader PSDs. At the same operatingconditions microemulsion-based granules were more brittle but rounder and showed smaller median diameter compared to water-based granules. The dissolution rate of simvastatin was not significantly affected by the operating conditions.
File in questo prodotto:
File Dimensione Formato  
Santomaso_PT2015.pdf

accesso aperto

Tipologia: Preprint (submitted version)
Licenza: Creative commons
Dimensione 844.15 kB
Formato Adobe PDF
844.15 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/3103099
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 16
social impact