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Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation
The purpose of the study was to develop Tizanidine HCl (TZN) and Meloxicam (MLX) loaded bilayer mucoadhesive films intended for buccal administration, aiming to enhance the bioavailability. Bilayer films were prepared by solvent evaporation technique selecting arabinoxylan (ARX) as a sustained relea...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864138/ https://www.ncbi.nlm.nih.gov/pubmed/29566073 http://dx.doi.org/10.1371/journal.pone.0194410 |
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author | Zaman, Muhammad Hanif, Muhammad Shaheryar, Zaib Ali |
author_facet | Zaman, Muhammad Hanif, Muhammad Shaheryar, Zaib Ali |
author_sort | Zaman, Muhammad |
collection | PubMed |
description | The purpose of the study was to develop Tizanidine HCl (TZN) and Meloxicam (MLX) loaded bilayer mucoadhesive films intended for buccal administration, aiming to enhance the bioavailability. Bilayer films were prepared by solvent evaporation technique selecting arabinoxylan (ARX) as a sustained release (SR) layer forming polymer and hydroxypropyl methylcellulose (HPMC) E-15 as an immediate release (IR) layer-forming polymer. Prepared films were subjected to in-vitro drug release, surface morphology, mechanical strength, compatibility of the ingredients, drug contents, ex-vivo mucoadhesion strength and drug permeation. Crossover study design was applied to study the in-vivo pharmacokinetics by using albino rabbits. Various pharmacokinetic parameters including AUC, C(max), t(max) and t(1/2) of both drugs loaded in films were compared with standard solution/dispersion administered to the rabbits at the dose of 1mg/kg. The results unveiled instant release and permeation of MLX from IR layer, while good controlled release and permeation characteristics of TZN from SR films over 8 h. films were of uniform thickness with smooth surface and satisfactory mechanical strength. Mucoadhesion strength was sufficient to provide suitable contact time with mucosal membrane. The pharmacokinetic study exhibited prompt absorption of MLX with better AUC (0-t) (6655.64 ng/ml*h vs 6538.99 ng/ml*h) and C(max) (436.98 ng/ml vs 411.33 ng/ml) from oral dispersion. Similarly buccal films has shown enhanced half-life (9.91hr vs 2.51 hr), AUC (0-t) (1043.4 ng/ml*h vs 149.1 ng/ml*h) and C(max) (91.92 ng/ml vs 42.29 ng/ml) from oral solution. A statistical investigation disclosed a significantly improved pharmacokinetics of TZN and MLX after their absorption across buccal route following administration of buccal film (p<0.05). ARX proved expedient and bilayer buccal films as a drug delivery system ascertained the dual effect of providing instant release of one active agent and persistent release of another one with improved pharmacokinetics. |
format | Online Article Text |
id | pubmed-5864138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58641382018-03-28 Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation Zaman, Muhammad Hanif, Muhammad Shaheryar, Zaib Ali PLoS One Research Article The purpose of the study was to develop Tizanidine HCl (TZN) and Meloxicam (MLX) loaded bilayer mucoadhesive films intended for buccal administration, aiming to enhance the bioavailability. Bilayer films were prepared by solvent evaporation technique selecting arabinoxylan (ARX) as a sustained release (SR) layer forming polymer and hydroxypropyl methylcellulose (HPMC) E-15 as an immediate release (IR) layer-forming polymer. Prepared films were subjected to in-vitro drug release, surface morphology, mechanical strength, compatibility of the ingredients, drug contents, ex-vivo mucoadhesion strength and drug permeation. Crossover study design was applied to study the in-vivo pharmacokinetics by using albino rabbits. Various pharmacokinetic parameters including AUC, C(max), t(max) and t(1/2) of both drugs loaded in films were compared with standard solution/dispersion administered to the rabbits at the dose of 1mg/kg. The results unveiled instant release and permeation of MLX from IR layer, while good controlled release and permeation characteristics of TZN from SR films over 8 h. films were of uniform thickness with smooth surface and satisfactory mechanical strength. Mucoadhesion strength was sufficient to provide suitable contact time with mucosal membrane. The pharmacokinetic study exhibited prompt absorption of MLX with better AUC (0-t) (6655.64 ng/ml*h vs 6538.99 ng/ml*h) and C(max) (436.98 ng/ml vs 411.33 ng/ml) from oral dispersion. Similarly buccal films has shown enhanced half-life (9.91hr vs 2.51 hr), AUC (0-t) (1043.4 ng/ml*h vs 149.1 ng/ml*h) and C(max) (91.92 ng/ml vs 42.29 ng/ml) from oral solution. A statistical investigation disclosed a significantly improved pharmacokinetics of TZN and MLX after their absorption across buccal route following administration of buccal film (p<0.05). ARX proved expedient and bilayer buccal films as a drug delivery system ascertained the dual effect of providing instant release of one active agent and persistent release of another one with improved pharmacokinetics. Public Library of Science 2018-03-22 /pmc/articles/PMC5864138/ /pubmed/29566073 http://dx.doi.org/10.1371/journal.pone.0194410 Text en © 2018 Zaman et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zaman, Muhammad Hanif, Muhammad Shaheryar, Zaib Ali Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation |
title | Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation |
title_full | Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation |
title_fullStr | Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation |
title_full_unstemmed | Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation |
title_short | Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation |
title_sort | development of tizanidine hcl-meloxicam loaded mucoadhesive buccal films: in-vitro and in-vivo evaluation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864138/ https://www.ncbi.nlm.nih.gov/pubmed/29566073 http://dx.doi.org/10.1371/journal.pone.0194410 |
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