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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

ANOVA results of PS and EE as responses.Notes: 3D plots showing the effect of independent variables on responses Y1 (A–C) and Y2 (D–F). (G and H) Linear correlation plot between actual and predicted values for response Y1 and Y2. (I and J) Corresponding residual plot for response Y1 and Y2. PS (Y1) =Particle size and EE (Y2) =Entrapment efficiency.Abbreviations: AP, aqueous phase; 3D, three dimensional.
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f2-ijn-11-2901: ANOVA results of PS and EE as responses.Notes: 3D plots showing the effect of independent variables on responses Y1 (A–C) and Y2 (D–F). (G and H) Linear correlation plot between actual and predicted values for response Y1 and Y2. (I and J) Corresponding residual plot for response Y1 and Y2. PS (Y1) =Particle size and EE (Y2) =Entrapment efficiency.Abbreviations: AP, aqueous phase; 3D, three dimensional.

Mentions: The three-dimensional surface plots for PS (Figure 2A–C) and EE (Figure 2D–F) were used to demonstrate the relationship and interaction between the coded/actual independent variables and the responses.25 This shows that there was a decrease in PS and an increase in EE with a decrease in the amount of lipid and an increase in the amount of surfactant and volume of AP. Mathematical models describing the relationship between variables (A, B, and C) and responses (Y1 and Y2) could be reduced to Equations 6 and 7, respectively.Particlesize(Y1)=99.062−13.155A+34.9113B−10.6663C−16.8475AB+27.1375AC−27.16BC+18.3015A2+66.739B2+43.084C2(6)Entrapmentefficiency(Y2)=82+2.5A+4.5B+2C−3.25AC+4.25BC−2.625A2−6.125B2−15.625C2(7)


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)

ANOVA results of PS and EE as responses.Notes: 3D plots showing the effect of independent variables on responses Y1 (A–C) and Y2 (D–F). (G and H) Linear correlation plot between actual and predicted values for response Y1 and Y2. (I and J) Corresponding residual plot for response Y1 and Y2. PS (Y1) =Particle size and EE (Y2) =Entrapment efficiency.Abbreviations: AP, aqueous phase; 3D, three dimensional.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-11-2901: ANOVA results of PS and EE as responses.Notes: 3D plots showing the effect of independent variables on responses Y1 (A–C) and Y2 (D–F). (G and H) Linear correlation plot between actual and predicted values for response Y1 and Y2. (I and J) Corresponding residual plot for response Y1 and Y2. PS (Y1) =Particle size and EE (Y2) =Entrapment efficiency.Abbreviations: AP, aqueous phase; 3D, three dimensional.
Mentions: The three-dimensional surface plots for PS (Figure 2A–C) and EE (Figure 2D–F) were used to demonstrate the relationship and interaction between the coded/actual independent variables and the responses.25 This shows that there was a decrease in PS and an increase in EE with a decrease in the amount of lipid and an increase in the amount of surfactant and volume of AP. Mathematical models describing the relationship between variables (A, B, and C) and responses (Y1 and Y2) could be reduced to Equations 6 and 7, respectively.Particlesize(Y1)=99.062−13.155A+34.9113B−10.6663C−16.8475AB+27.1375AC−27.16BC+18.3015A2+66.739B2+43.084C2(6)Entrapmentefficiency(Y2)=82+2.5A+4.5B+2C−3.25AC+4.25BC−2.625A2−6.125B2−15.625C2(7)

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