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Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation
Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920237/ https://www.ncbi.nlm.nih.gov/pubmed/27382279 http://dx.doi.org/10.2147/IJN.S94658 |
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author | Nidhi, Malviya Patro, M Nagaraju Kusumvalli, Somisetty Kusumdevi, Vemula |
author_facet | Nidhi, Malviya Patro, M Nagaraju Kusumvalli, Somisetty Kusumdevi, Vemula |
author_sort | Nidhi, Malviya |
collection | PubMed |
description | Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion–evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box–Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN “S8” were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C(max) and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized. |
format | Online Article Text |
id | pubmed-4920237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49202372016-07-05 Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation Nidhi, Malviya Patro, M Nagaraju Kusumvalli, Somisetty Kusumdevi, Vemula Int J Nanomedicine Original Research Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion–evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box–Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN “S8” were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C(max) and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized. Dove Medical Press 2016-06-20 /pmc/articles/PMC4920237/ /pubmed/27382279 http://dx.doi.org/10.2147/IJN.S94658 Text en © 2016 Nidhi et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Nidhi, Malviya Patro, M Nagaraju Kusumvalli, Somisetty Kusumdevi, Vemula Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
title | Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
title_full | Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
title_fullStr | Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
title_full_unstemmed | Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
title_short | Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
title_sort | development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920237/ https://www.ncbi.nlm.nih.gov/pubmed/27382279 http://dx.doi.org/10.2147/IJN.S94658 |
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