In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir. / He, Shaolong; Nielsen, Carsten Uhd; Mu, Huiling; Jacobsen, Jette.

In: Journal of Drug Delivery Science and Technology, Vol. 78, 103954, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

He, S, Nielsen, CU, Mu, H & Jacobsen, J 2022, 'In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir', Journal of Drug Delivery Science and Technology, vol. 78, 103954. https://doi.org/10.1016/j.jddst.2022.103954

APA

He, S., Nielsen, C. U., Mu, H., & Jacobsen, J. (2022). In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir. Journal of Drug Delivery Science and Technology, 78, [103954]. https://doi.org/10.1016/j.jddst.2022.103954

Vancouver

He S, Nielsen CU, Mu H, Jacobsen J. In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir. Journal of Drug Delivery Science and Technology. 2022;78. 103954. https://doi.org/10.1016/j.jddst.2022.103954

Author

He, Shaolong ; Nielsen, Carsten Uhd ; Mu, Huiling ; Jacobsen, Jette. / In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir. In: Journal of Drug Delivery Science and Technology. 2022 ; Vol. 78.

Bibtex

@article{6033295287df4b968e9d871bfafc913f,
title = "In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir",
abstract = "Buccal delivery of saquinavir has the advantage to bypass the hepatic first-pass metabolism associated with oral administration. Local microenvironmental pH (pHM) modification at the buccal mucosa might increase absorption of saquinavir by balancing the solubility and partition of saquinavir into the buccal mucosa. The present study aimed to evaluate a novel saquinavir pHM modifying buccal film using effervescence, as well as to elucidate the relationship between pHM and permeation of saquinavir released from the buccal films. Hydroxypropyl methylcellulose-based films were prepared: 1) a bilayered effervescent film composed of an alkaline layer and a layer containing saquinavir and malic acid, 2) a monolayered film composed of saquinavir and malic acid (pHM modifying film), and 3) a monolayered film composed of saquinvir (control). The release of saquinavir from these films and permeation of saquinavir across porcine mucosae were evaluated. The monolayered pHM modifying film led to a decrease in pHM from pH 6.8 to 3.0 after 5.5 min, while the effervescent film had an initial decrease in pHM (from pH 6.8 to 4.0) caused by the co-release of malic acid and a subsequent pHM increase (from pH 4.0 to 5.9) caused by the release of carbonate from the alkaline layer within 15 min. Saquinavir released faster from the pHM modifying film than from the effervescent film. However, a higher permeation of saquinavir and mucosal accumulation was observed for the effervescent film. This could be attributed to the higher concentration of ionized specie and a faster tissue partitioning of unionized saquinavir, respectively. These results suggest that effervescent pHM modifying film is a potential formulation strategy for buccal delivery of saquinavir.",
keywords = "Buccal delivery, Effervescence, pH modification, Saquinavir",
author = "Shaolong He and Nielsen, {Carsten Uhd} and Huiling Mu and Jette Jacobsen",
note = "Funding Information: We acknowledge the China Scholarship Council (201708510087) for financial support to Shaolong He and the technical support from Rita Wulff Rasmussen, S{\o}ren Michael Nielsen, Jan G{\o}ral, Yang Hwan Yun and Mette Frandsen. We also acknowledge Susan Weng Larsen for the guidance of UV-HPLC analysis. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
doi = "10.1016/j.jddst.2022.103954",
language = "English",
volume = "78",
journal = "Journal of Drug Delivery Science and Technology",
issn = "1773-2247",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - In vitro and ex vivo evaluation of bilayered effervescent microenvironmental pH modifying buccal films with saquinavir

AU - He, Shaolong

AU - Nielsen, Carsten Uhd

AU - Mu, Huiling

AU - Jacobsen, Jette

N1 - Funding Information: We acknowledge the China Scholarship Council (201708510087) for financial support to Shaolong He and the technical support from Rita Wulff Rasmussen, Søren Michael Nielsen, Jan Gøral, Yang Hwan Yun and Mette Frandsen. We also acknowledge Susan Weng Larsen for the guidance of UV-HPLC analysis. Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - Buccal delivery of saquinavir has the advantage to bypass the hepatic first-pass metabolism associated with oral administration. Local microenvironmental pH (pHM) modification at the buccal mucosa might increase absorption of saquinavir by balancing the solubility and partition of saquinavir into the buccal mucosa. The present study aimed to evaluate a novel saquinavir pHM modifying buccal film using effervescence, as well as to elucidate the relationship between pHM and permeation of saquinavir released from the buccal films. Hydroxypropyl methylcellulose-based films were prepared: 1) a bilayered effervescent film composed of an alkaline layer and a layer containing saquinavir and malic acid, 2) a monolayered film composed of saquinavir and malic acid (pHM modifying film), and 3) a monolayered film composed of saquinvir (control). The release of saquinavir from these films and permeation of saquinavir across porcine mucosae were evaluated. The monolayered pHM modifying film led to a decrease in pHM from pH 6.8 to 3.0 after 5.5 min, while the effervescent film had an initial decrease in pHM (from pH 6.8 to 4.0) caused by the co-release of malic acid and a subsequent pHM increase (from pH 4.0 to 5.9) caused by the release of carbonate from the alkaline layer within 15 min. Saquinavir released faster from the pHM modifying film than from the effervescent film. However, a higher permeation of saquinavir and mucosal accumulation was observed for the effervescent film. This could be attributed to the higher concentration of ionized specie and a faster tissue partitioning of unionized saquinavir, respectively. These results suggest that effervescent pHM modifying film is a potential formulation strategy for buccal delivery of saquinavir.

AB - Buccal delivery of saquinavir has the advantage to bypass the hepatic first-pass metabolism associated with oral administration. Local microenvironmental pH (pHM) modification at the buccal mucosa might increase absorption of saquinavir by balancing the solubility and partition of saquinavir into the buccal mucosa. The present study aimed to evaluate a novel saquinavir pHM modifying buccal film using effervescence, as well as to elucidate the relationship between pHM and permeation of saquinavir released from the buccal films. Hydroxypropyl methylcellulose-based films were prepared: 1) a bilayered effervescent film composed of an alkaline layer and a layer containing saquinavir and malic acid, 2) a monolayered film composed of saquinavir and malic acid (pHM modifying film), and 3) a monolayered film composed of saquinvir (control). The release of saquinavir from these films and permeation of saquinavir across porcine mucosae were evaluated. The monolayered pHM modifying film led to a decrease in pHM from pH 6.8 to 3.0 after 5.5 min, while the effervescent film had an initial decrease in pHM (from pH 6.8 to 4.0) caused by the co-release of malic acid and a subsequent pHM increase (from pH 4.0 to 5.9) caused by the release of carbonate from the alkaline layer within 15 min. Saquinavir released faster from the pHM modifying film than from the effervescent film. However, a higher permeation of saquinavir and mucosal accumulation was observed for the effervescent film. This could be attributed to the higher concentration of ionized specie and a faster tissue partitioning of unionized saquinavir, respectively. These results suggest that effervescent pHM modifying film is a potential formulation strategy for buccal delivery of saquinavir.

KW - Buccal delivery

KW - Effervescence

KW - pH modification

KW - Saquinavir

U2 - 10.1016/j.jddst.2022.103954

DO - 10.1016/j.jddst.2022.103954

M3 - Journal article

AN - SCOPUS:85144319743

VL - 78

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

SN - 1773-2247

M1 - 103954

ER -

ID: 331583537