Microenvironmental pH modifying films for buccal delivery of saquinavir: Effects of organic acids on pH and drug release in vitro
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Microenvironmental pH modifying films for buccal delivery of saquinavir : Effects of organic acids on pH and drug release in vitro. / He, Shaolong; Østergaard, Jesper; Ashna, Madina; Nielsen, Carsten Uhd; Jacobsen, Jette; Mu, Huiling.
In: International Journal of Pharmaceutics, Vol. 585, 119567, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Microenvironmental pH modifying films for buccal delivery of saquinavir
T2 - Effects of organic acids on pH and drug release in vitro
AU - He, Shaolong
AU - Østergaard, Jesper
AU - Ashna, Madina
AU - Nielsen, Carsten Uhd
AU - Jacobsen, Jette
AU - Mu, Huiling
N1 - Copyright © 2020 Elsevier B.V. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Buccal delivery of saquinavir has the advantage to bypass the gastrointestinal enzymatic degradation and the hepatic first-pass metabolism. Saquinavir has a pH-dependent solubility and is poorly soluble in human saliva at the physiological pH. Decreasing microenvironmental pH (pHM) in saliva may increase saquinavir release from buccal formulations. The present study aimed to investigate the effects of organic acids on the pHM, saquinavir release in vitro and the solid-state form of saquinavir. An UV/Vis imaging method was used to measure pHM. After 5 min of swelling of the buccal films containing malic acid, pHM was reduced from 6.8 to 5.4. The films containing malic acid were more efficient in maintaining low pHM than films containing citric acid and succinic acid. Addition of organic acids in the buccal films resulted in a faster drug release than films without acids due to the reduced pHM. However, the enhancement of saquinavir release was limited by the fast release of organic acids. Addition of malic acid and citric acid suppressed the crystallization of saquinavir during 3 months storage at the elevated temperature (40 °C) and humidity (RH 75%) respectively. These results suggest that pHM modifying film is a potential formulation strategy for buccal delivery of saquinavir.
AB - Buccal delivery of saquinavir has the advantage to bypass the gastrointestinal enzymatic degradation and the hepatic first-pass metabolism. Saquinavir has a pH-dependent solubility and is poorly soluble in human saliva at the physiological pH. Decreasing microenvironmental pH (pHM) in saliva may increase saquinavir release from buccal formulations. The present study aimed to investigate the effects of organic acids on the pHM, saquinavir release in vitro and the solid-state form of saquinavir. An UV/Vis imaging method was used to measure pHM. After 5 min of swelling of the buccal films containing malic acid, pHM was reduced from 6.8 to 5.4. The films containing malic acid were more efficient in maintaining low pHM than films containing citric acid and succinic acid. Addition of organic acids in the buccal films resulted in a faster drug release than films without acids due to the reduced pHM. However, the enhancement of saquinavir release was limited by the fast release of organic acids. Addition of malic acid and citric acid suppressed the crystallization of saquinavir during 3 months storage at the elevated temperature (40 °C) and humidity (RH 75%) respectively. These results suggest that pHM modifying film is a potential formulation strategy for buccal delivery of saquinavir.
U2 - 10.1016/j.ijpharm.2020.119567
DO - 10.1016/j.ijpharm.2020.119567
M3 - Journal article
C2 - 32585177
VL - 585
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 119567
ER -
ID: 245235681