TY - JOUR

T1 - Exploration of in vitro drug release testing methods for saquinavir microenvironmental pH modifying buccal films

AU - He, Shaolong

AU - Jacobsen, Jette

AU - Nielsen, Carsten Uhd

AU - Genina, Natalja

AU - Østergaard, Jesper

AU - Mu, Huiling

N1 - Funding Information: Shaolong He acknowledges the China Scholarship Council ( 201708510087 ) for financial support and the technical support from Søren Michael Nielsen, Rita Wulff Rasmussen, Jens Graff, Mette Frandsen and Dorthe Ørbæk.

PY - 2021

Y1 - 2021

N2 - Buccal films containing a pH modifying excipient may be able to increase bioavailability of drugs with pH-dependent solubility such as saquinavir. Access to suitable in vitro drug release testing methods may facilitate buccal formulation development. This study aimed to explore two release testing methods for characterising buccal films and to elucidate the relationship between microenvironmental pH (pHM, i.e. the pH around the swelling films) and saquinavir release. The Franz diffusion cell method was applicable to investigate the effect of hydroxypropyl methylcellulose (HPMC) grade on saquinavir release. Films containing HPMC K3 LV had a faster saquinavir release than films containing HPMC K100 LV. A UV/Vis imaging method was developed to visualise saquinavir release and pHM changes during the initial dissolution. Within 5 min, the pHM decreased from 6.8 to around 5.4 for HPMC K100 LV-based films containing 11.1 % or 16.6 % (w/w) malic acid. Subsequently, the pHM increased due to increasing concentrations of saquinavir. An increase in malic acid content led to a faster saquinavir release. The combination of methods may be broadly applicable for excipient screening in development of buccal formulations. The imaging approach holds promise for characterizing other pH modifying formulation principles.

AB - Buccal films containing a pH modifying excipient may be able to increase bioavailability of drugs with pH-dependent solubility such as saquinavir. Access to suitable in vitro drug release testing methods may facilitate buccal formulation development. This study aimed to explore two release testing methods for characterising buccal films and to elucidate the relationship between microenvironmental pH (pHM, i.e. the pH around the swelling films) and saquinavir release. The Franz diffusion cell method was applicable to investigate the effect of hydroxypropyl methylcellulose (HPMC) grade on saquinavir release. Films containing HPMC K3 LV had a faster saquinavir release than films containing HPMC K100 LV. A UV/Vis imaging method was developed to visualise saquinavir release and pHM changes during the initial dissolution. Within 5 min, the pHM decreased from 6.8 to around 5.4 for HPMC K100 LV-based films containing 11.1 % or 16.6 % (w/w) malic acid. Subsequently, the pHM increased due to increasing concentrations of saquinavir. An increase in malic acid content led to a faster saquinavir release. The combination of methods may be broadly applicable for excipient screening in development of buccal formulations. The imaging approach holds promise for characterizing other pH modifying formulation principles.

KW - Drug release testing method

KW - Franz diffusion cell

KW - Microenvironmental pH

KW - Saquinavir buccal film

KW - UV/Vis imaging

U2 - 10.1016/j.ejps.2021.105867

DO - 10.1016/j.ejps.2021.105867

M3 - Journal article

C2 - 33951482

AN - SCOPUS:85105881112

VL - 163

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

M1 - 105867

ER -