NDLI: Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

Content Provider	Springer Nature Link
Author	Xia, Binfeng Yang, Zhen Zhou, Haiying Lukacova, Viera Zhu, Wei Milewski, Mikolaj Kesisoglou, Filippos
Copyright Year	2015
Abstract	Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo® sublingual tablets (zolpidem tartrate). The model was evaluated by the goodness-of-fit between simulated and observed concentrations and the deviation of key PK parameters (e.g., C $_{max}$, T $_{max}$, and AUC). In addition, a sensitivity analysis was conducted to demonstrate the interplay and impact of key modeling parameters on the fraction absorbed via oral mucosa (F $_{a_IO}$). The OCCAT™ model captured the observed pharmacokinetics for Intermezzo® sublingual tablets (R $^{2}$ > 0.9). The predicted deviations (%) for C $_{max}$, AUC$_{0–inf}$, AUC$_{0–20 min}$, and T $_{max}$ were 5.7, 28.0, 11.8, and 28.6%, respectively, indicating good prediction accuracy. The model also estimated ~18% of total drug was absorbed via the IO route. Furthermore, the sensitivity analysis indicated that the F $_{a_IO}$ was not only associated with drug diffusivity and unbound fraction in epithelium tissue (f $_{ut}$) but also depended on the physicochemical properties of compounds for IO delivery (e.g., solubility and logD $_{pH = 7.4}$). The novel physiologically based IO absorption OCCAT™ model showed satisfactory performance and will be helpful to guide development of future intraoral formulations.
Starting Page	631
Ending Page	642
Page Count	12
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	17
Issue Number	3
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2015-02-26
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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