Next generation of buccadhesive excipient: Preactivated carboxymethyl cellulose

Flavia Laffleur; Lukas Bacher; Stefan Vanicek; Claudia Menzel; Ijaz Muhammad

doi:10.1016/j.ijpharm.2016.01.012

Next generation of buccadhesive excipient: Preactivated carboxymethyl cellulose

Int J Pharm. 2016 Mar 16;500(1-2):120-7. doi: 10.1016/j.ijpharm.2016.01.012. Epub 2016 Jan 7.

Authors

Flavia Laffleur¹, Lukas Bacher², Stefan Vanicek³, Claudia Menzel², Ijaz Muhammad²

Affiliations

¹ Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria. Electronic address: Flavia.Laffleur@uibk.ac.at.
² Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria.
³ Institute for Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria.

PMID: 26773600
DOI: 10.1016/j.ijpharm.2016.01.012

Abstract

Aim: Assessment of preactivated carboxymethyl cellulose as potential excipient for buccal drug delivery.

Methods: Firstly, carboxymethyl cellulose (CMC) and cysteine (SH) were covalently coupled via amide bond formation to obtain thiolated carboxymethyl cellulose (CMC-SH). Further, preactivated carboxymethyl cellulose (CMC-S-S-MNA) was obtained by preactivation with 2-mercaptonicotinic acid (MNA). Sulforhodamine 101 (SRH101) was used as a model drug for permeation study through buccal mucosa. CMC-S-S-MNA was evaluated with respect to mucoadhesive and permeation enhancing effect and cytotoxicity.

Results: Thiolated carboxymethyl cellulose exhibited a total amount of 112.46 ± 0.46 thiol groups. CMC-S-S-MNA exhibited around 50% of preactivated thiol groups. The preactivated polymer showed no toxic effect. Furthermore, compared to unmodified CMC, CMC-S-S-MNA revealed 3.0-fold improved mucoadhesive properties according to the rotating cylinder method and 8.8-fold enhancement in mucoadhesiveness by tensile assay, respectively.

Conclusion: Preactivated carboxymethyl cellulose fulfills the requirements as potential excipient of being mucoadhesive and permeation enhancing for the buccal drug delivery.

Keywords: Buccal; Carboxymethyl cellulose; Mucosa; Preactivation; Thiomers.

MeSH terms

Adhesiveness
Animals
Caco-2 Cells
Carboxymethylcellulose Sodium* / administration & dosage
Carboxymethylcellulose Sodium* / chemistry
Carboxymethylcellulose Sodium* / pharmacology
Cell Survival / drug effects
Coloring Agents / administration & dosage
Coloring Agents / chemistry
Coloring Agents / pharmacology
Cysteine* / administration & dosage
Cysteine* / chemistry
Cysteine* / pharmacology
Drug Carriers* / administration & dosage
Drug Carriers* / chemistry
Drug Carriers* / pharmacology
Excipients* / administration & dosage
Excipients* / chemistry
Excipients* / pharmacology
Humans
In Vitro Techniques
Mouth Mucosa / metabolism*
Rhodamines / administration & dosage
Rhodamines / chemistry
Rhodamines / pharmacology
Swine

Substances

Coloring Agents
Drug Carriers
Excipients
Rhodamines
sulforhodamine 101
Carboxymethylcellulose Sodium
Cysteine