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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

Physicochemical characterization of DDEA-SLN, TP, physical mixtures and excipients.Notes: (A) DSC thermograms of (a) DDEA; (b) Compritol ATO 888; (c) Precirol ATO 5; (d) Geleol; (e) PA; (f) SA; (g) melted Compritol with DDEA; (h) melted Precirol with DDEA; (i) melted Geleol with DDEA; (j) melted PA with DDEA; (k) melted SA containing DDEA; (l) melted mixture of Precirol and Geleol containing DDEA; (m) DDEA-SLN; (n) LB; (o) physical mixture of LB and DDEA and HPC-LF; (p) TP. (B) FTIR spectrum of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) melted mixture of Precirol and Geleol containing DDEA; (e) DDEA-SLN; (f) LB; (g) physical mixture of LB, DDEA, and HPC-LF; (h) TP. (C) XRD diffractograms of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) SLN; (e) LB; (f) physical mixture of LB, DDEA, and HPC-LF; (g) TP.Abbreviations: DDEA, diclofenac diethylamine; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared spectrophotometry; HPC, hydroxypropyl cellulose; LB, lignocaine base; PA, palmitic acid; SLN, solid lipid nanoparticle; TP, transmucosal patch; XRD, X-ray diffraction; SA, stearic acid.
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f1-ijn-11-2901: Physicochemical characterization of DDEA-SLN, TP, physical mixtures and excipients.Notes: (A) DSC thermograms of (a) DDEA; (b) Compritol ATO 888; (c) Precirol ATO 5; (d) Geleol; (e) PA; (f) SA; (g) melted Compritol with DDEA; (h) melted Precirol with DDEA; (i) melted Geleol with DDEA; (j) melted PA with DDEA; (k) melted SA containing DDEA; (l) melted mixture of Precirol and Geleol containing DDEA; (m) DDEA-SLN; (n) LB; (o) physical mixture of LB and DDEA and HPC-LF; (p) TP. (B) FTIR spectrum of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) melted mixture of Precirol and Geleol containing DDEA; (e) DDEA-SLN; (f) LB; (g) physical mixture of LB, DDEA, and HPC-LF; (h) TP. (C) XRD diffractograms of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) SLN; (e) LB; (f) physical mixture of LB, DDEA, and HPC-LF; (g) TP.Abbreviations: DDEA, diclofenac diethylamine; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared spectrophotometry; HPC, hydroxypropyl cellulose; LB, lignocaine base; PA, palmitic acid; SLN, solid lipid nanoparticle; TP, transmucosal patch; XRD, X-ray diffraction; SA, stearic acid.

Mentions: Solubility of DDEA was determined in various lipids by DSC method. Figure 1A shows the thermograms of DDEA, lipids, and DDEA–lipid mixture and Table 1 illustrates melting point analysis. Characteristic melting point peak of DDEA (149.08°C) disappeared in all the mixtures, which indicated that the drug is soluble in all the lipids,23 namely, Compritol, Precirol, Geleol, PA, and stearic acid. But only in the case of Precirol and Geleol, maximum depression in melting point of the lipids was observed, indicating that DDEA is more soluble in these and comparatively less soluble in other lipids, and hence these were selected for preparation of DDEA-SLN.


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)

Physicochemical characterization of DDEA-SLN, TP, physical mixtures and excipients.Notes: (A) DSC thermograms of (a) DDEA; (b) Compritol ATO 888; (c) Precirol ATO 5; (d) Geleol; (e) PA; (f) SA; (g) melted Compritol with DDEA; (h) melted Precirol with DDEA; (i) melted Geleol with DDEA; (j) melted PA with DDEA; (k) melted SA containing DDEA; (l) melted mixture of Precirol and Geleol containing DDEA; (m) DDEA-SLN; (n) LB; (o) physical mixture of LB and DDEA and HPC-LF; (p) TP. (B) FTIR spectrum of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) melted mixture of Precirol and Geleol containing DDEA; (e) DDEA-SLN; (f) LB; (g) physical mixture of LB, DDEA, and HPC-LF; (h) TP. (C) XRD diffractograms of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) SLN; (e) LB; (f) physical mixture of LB, DDEA, and HPC-LF; (g) TP.Abbreviations: DDEA, diclofenac diethylamine; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared spectrophotometry; HPC, hydroxypropyl cellulose; LB, lignocaine base; PA, palmitic acid; SLN, solid lipid nanoparticle; TP, transmucosal patch; XRD, X-ray diffraction; SA, stearic acid.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-11-2901: Physicochemical characterization of DDEA-SLN, TP, physical mixtures and excipients.Notes: (A) DSC thermograms of (a) DDEA; (b) Compritol ATO 888; (c) Precirol ATO 5; (d) Geleol; (e) PA; (f) SA; (g) melted Compritol with DDEA; (h) melted Precirol with DDEA; (i) melted Geleol with DDEA; (j) melted PA with DDEA; (k) melted SA containing DDEA; (l) melted mixture of Precirol and Geleol containing DDEA; (m) DDEA-SLN; (n) LB; (o) physical mixture of LB and DDEA and HPC-LF; (p) TP. (B) FTIR spectrum of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) melted mixture of Precirol and Geleol containing DDEA; (e) DDEA-SLN; (f) LB; (g) physical mixture of LB, DDEA, and HPC-LF; (h) TP. (C) XRD diffractograms of (a) DDEA; (b) Precirol ATO 5; (c) Geleol; (d) SLN; (e) LB; (f) physical mixture of LB, DDEA, and HPC-LF; (g) TP.Abbreviations: DDEA, diclofenac diethylamine; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared spectrophotometry; HPC, hydroxypropyl cellulose; LB, lignocaine base; PA, palmitic acid; SLN, solid lipid nanoparticle; TP, transmucosal patch; XRD, X-ray diffraction; SA, stearic acid.
Mentions: Solubility of DDEA was determined in various lipids by DSC method. Figure 1A shows the thermograms of DDEA, lipids, and DDEA–lipid mixture and Table 1 illustrates melting point analysis. Characteristic melting point peak of DDEA (149.08°C) disappeared in all the mixtures, which indicated that the drug is soluble in all the lipids,23 namely, Compritol, Precirol, Geleol, PA, and stearic acid. But only in the case of Precirol and Geleol, maximum depression in melting point of the lipids was observed, indicating that DDEA is more soluble in these and comparatively less soluble in other lipids, and hence these were selected for preparation of DDEA-SLN.

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