Buccal Absorption of Biopharmaceutics Classification System III Drugs: Formulation Approaches and Mechanistic Insights

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2025 Jan 8

PMID 39771541

Authors

Rayan Sabra

Daniel Kirby

Vikram Chouk

Kleta Malgorzata

Afzal R Mohammed

Affiliations

Soon will be listed here.

Abstract

Buccal drug delivery emerges as a promising strategy to enhance the absorption of drugs classified under the Biopharmaceutics Classification System (BCS) Class III, characterized by high solubility and low permeability. However, addressing the absorption challenges of BCS Class III drugs necessitates innovative formulation strategies. This review delves into optimizing buccal drug delivery for BCS III drugs, focusing on various formulation approaches to improve absorption. Strategies such as permeation enhancers, mucoadhesive polymers, pH modifiers, ion pairing, and prodrugs are systematically explored for their potential to overcome challenges associated with BCS Class III drugs. The mechanistic insight into how these strategies influence drug absorption is discussed, providing a detailed understanding of their applicability. Furthermore, the review advocates for integrating conventional buccal dosage forms with these formulation approaches as a potential strategy to enhance absorption. By emphasizing bioavailability enhancement, this review contributes to a holistic understanding of optimizing buccal absorption for BCS Class III drugs, presenting a unified approach to overcome inherent limitations in their delivery.

References

Masson M, Loftsson T, Masson G, Stefansson E . Cyclodextrins as permeation enhancers: some theoretical evaluations and in vitro testing. J Control Release. 1999; 59(1):107-18. DOI: 10.1016/s0168-3659(98)00182-5. View

Figueiras A, Pais A, Veiga F . A comprehensive development strategy in buccal drug delivery. AAPS PharmSciTech. 2010; 11(4):1703-12. PMC: 3011081. DOI: 10.1208/s12249-010-9546-1. View

Sahni J, Raj S, Ahmad F, Khar R . Design and in vitro characterization of buccoadhesive drug delivery system of insulin. Indian J Pharm Sci. 2010; 70(1):61-5. PMC: 2852063. DOI: 10.4103/0250-474X.40333. View

Samiei N, Shafaati A, Zarghi A, Moghimi H, Foroutan S . Enhancement and in vitro evaluation of amifostine permeation through artificial membrane (PAMPA) via ion pairing approach and mechanistic selection of its optimal counter ion. Eur J Pharm Sci. 2013; 51:218-23. DOI: 10.1016/j.ejps.2013.10.002. View

He S, Mu H . Microenvironmental pH Modification in Buccal/Sublingual Dosage Forms for Systemic Drug Delivery. Pharmaceutics. 2023; 15(2). PMC: 9961113. DOI: 10.3390/pharmaceutics15020637. View

Sattar M, Sayed O, Lane M . Oral transmucosal drug delivery--current status and future prospects. Int J Pharm. 2014; 471(1-2):498-506. DOI: 10.1016/j.ijpharm.2014.05.043. View

Dahan A, Khamis M, Agbaria R, Karaman R . Targeted prodrugs in oral drug delivery: the modern molecular biopharmaceutical approach. Expert Opin Drug Deliv. 2012; 9(8):1001-13. DOI: 10.1517/17425247.2012.697055. View

Asad M, Rasul A, Abbas G, Shah M, Nazir I . Self-emulsifying drug delivery systems: A versatile approach to enhance the oral delivery of BCS class III drug via hydrophobic ion pairing. PLoS One. 2023; 18(6):e0286668. PMC: 10256195. DOI: 10.1371/journal.pone.0286668. View

Sharma N, Baldi A . Exploring versatile applications of cyclodextrins: an overview. Drug Deliv. 2014; 23(3):739-57. DOI: 10.3109/10717544.2014.938839. View

10.

AlQahtani M, Kazi M, Alsenaidy M, Ahmad M . Advances in Oral Drug Delivery. Front Pharmacol. 2021; 12:618411. PMC: 7933596. DOI: 10.3389/fphar.2021.618411. View

11.

Zhang H, Zhang J, Streisand J . Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002; 41(9):661-80. DOI: 10.2165/00003088-200241090-00003. View

12.

Jacob S, Nair A, Boddu S, Gorain B, Sreeharsha N, Shah J . An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems. Pharmaceutics. 2021; 13(8). PMC: 8399227. DOI: 10.3390/pharmaceutics13081206. View

13.

Wertz P . Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa. Int J Mol Sci. 2021; 22(10). PMC: 8155912. DOI: 10.3390/ijms22105229. View

14.

Dave V, Gupta D, Yu M, Nguyen P, Varghese Gupta S . Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules. Drug Dev Ind Pharm. 2016; 43(2):177-189. DOI: 10.1080/03639045.2016.1269122. View

15.

Salamat-Miller N, Chittchang M, Johnston T . The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev. 2005; 57(11):1666-91. DOI: 10.1016/j.addr.2005.07.003. View

16.

Pickering G, Macian N, Libert F, Cardot J, Coissard S, Perovitch P . Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers. Drug Des Devel Ther. 2014; 8:1621-7. PMC: 4189711. DOI: 10.2147/DDDT.S63476. View

17.

Dahan A, Zimmermann E, Ben-Shabat S . Modern prodrug design for targeted oral drug delivery. Molecules. 2014; 19(10):16489-505. PMC: 6271014. DOI: 10.3390/molecules191016489. View

18.

Shaikh R, Raghu Raj Singh T, Garland M, Woolfson A, Donnelly R . Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011; 3(1):89-100. PMC: 3053525. DOI: 10.4103/0975-7406.76478. View

19.

Yoo S, Yoon B, Lee H, Lee K . Increased bioavailability of clomipramine after sublingual administration in rats. J Pharm Sci. 1999; 88(11):1119-21. DOI: 10.1021/js990163p. View

20.

Hua S . Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration. Front Pharmacol. 2019; 10:1328. PMC: 6848967. DOI: 10.3389/fphar.2019.01328. View