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Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation.

Nidhi M, Patro MN, Kusumvalli S, Kusumdevi V - Int J Nanomedicine (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Al-Ameen College of Pharmacy.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

In vivo evaluation of TP.Notes: (A) GCF and (B) plasma concentration–time profile of LB and DDEA after application of TP (group 1) and of the control (group 2) (n=6).Abbreviations: DDEA, diclofenac diethylamine; Dic, diclofenac; GCF, gingival crevicular fluid; LB, lignocaine base; Lig, lignocaine; TP, transmucosal patch.
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f6-ijn-11-2901: In vivo evaluation of TP.Notes: (A) GCF and (B) plasma concentration–time profile of LB and DDEA after application of TP (group 1) and of the control (group 2) (n=6).Abbreviations: DDEA, diclofenac diethylamine; Dic, diclofenac; GCF, gingival crevicular fluid; LB, lignocaine base; Lig, lignocaine; TP, transmucosal patch.

Mentions: The GCF and plasma concentration–time profiles of LB and DDEA as represented in Figure 6 and Table 5 show the pharmacokinetic data. When applied as TP, the mean peak GCF concentration for Lig and Dic was 8.87-fold and 2.8-fold greater, respectively, whereas the area under the curve (AUC) of LB and DDEA in GCF was fivefold and 93-fold, respectively, greater when compared to GCF of the control. The mean peak plasma concentration of Lig was twofold greater and that of Dic was 202-fold lower, whereas the AUC of Lig was 8.6-fold greater and that of Dic was 1.1-fold lower in the case of TP when compared to the control. The GCF concentration of both the drugs was higher when compared to plasma concentration.32,33 The GCF represents the local availability of drugs present in the gingiva;33,34 also the absorption, accumulation, and permeation of Lig were rapid from TP representing comparatively higher concentration in GCF. Dic from TP was also absorbed and represented well in GCF signifying local accumulation, and hence comparatively lower plasma concentration was observed.32–34 Tissue concentrations (Table 6) of Lig and Dic were higher for the group receiving TP when compared to the control.


Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation.

Nidhi M, Patro MN, Kusumvalli S, Kusumdevi V - Int J Nanomedicine (2016)

In vivo evaluation of TP.Notes: (A) GCF and (B) plasma concentration–time profile of LB and DDEA after application of TP (group 1) and of the control (group 2) (n=6).Abbreviations: DDEA, diclofenac diethylamine; Dic, diclofenac; GCF, gingival crevicular fluid; LB, lignocaine base; Lig, lignocaine; TP, transmucosal patch.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4920237&req=5

f6-ijn-11-2901: In vivo evaluation of TP.Notes: (A) GCF and (B) plasma concentration–time profile of LB and DDEA after application of TP (group 1) and of the control (group 2) (n=6).Abbreviations: DDEA, diclofenac diethylamine; Dic, diclofenac; GCF, gingival crevicular fluid; LB, lignocaine base; Lig, lignocaine; TP, transmucosal patch.
Mentions: The GCF and plasma concentration–time profiles of LB and DDEA as represented in Figure 6 and Table 5 show the pharmacokinetic data. When applied as TP, the mean peak GCF concentration for Lig and Dic was 8.87-fold and 2.8-fold greater, respectively, whereas the area under the curve (AUC) of LB and DDEA in GCF was fivefold and 93-fold, respectively, greater when compared to GCF of the control. The mean peak plasma concentration of Lig was twofold greater and that of Dic was 202-fold lower, whereas the AUC of Lig was 8.6-fold greater and that of Dic was 1.1-fold lower in the case of TP when compared to the control. The GCF concentration of both the drugs was higher when compared to plasma concentration.32,33 The GCF represents the local availability of drugs present in the gingiva;33,34 also the absorption, accumulation, and permeation of Lig were rapid from TP representing comparatively higher concentration in GCF. Dic from TP was also absorbed and represented well in GCF signifying local accumulation, and hence comparatively lower plasma concentration was observed.32–34 Tissue concentrations (Table 6) of Lig and Dic were higher for the group receiving TP when compared to the control.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Al-Ameen College of Pharmacy.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus