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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

Papp ×10−6 of LB, DDEA, DDEA-SLN, and TP drugs from Caco-2 mono culture.Notes: All values are expressed as mean ± SEM (*P<0.05, **P<0.005, ***P<0.0005). Papp represents the apparent permeability.Abbreviations: DDEA, diclofenac diethylamine; LB, lignocaine base; SLN, solid lipid nanoparticle; SEM, standard error of the mean; TP, transmucosal patch; ex, extracted.
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f5-ijn-11-2901: Papp ×10−6 of LB, DDEA, DDEA-SLN, and TP drugs from Caco-2 mono culture.Notes: All values are expressed as mean ± SEM (*P<0.05, **P<0.005, ***P<0.0005). Papp represents the apparent permeability.Abbreviations: DDEA, diclofenac diethylamine; LB, lignocaine base; SLN, solid lipid nanoparticle; SEM, standard error of the mean; TP, transmucosal patch; ex, extracted.

Mentions: As shown in Figure 5, the permeability of LB present in TP was increased considerably when compared to the pure drug. This could be due to the presence of permeation enhancers LPG and clove oil, which loosen the lipid bilayer of the cell membrane and facilitate the movement of lipophilic drugs across the membrane. The permeability of DDEA was found to decrease when analyzed by filtering the collected media across 0.22 μm membrane. However, when the collected media were analyzed after extracting the DDEA from SLN the apparent permeability was found to be enhanced significantly. This phenomenon could be explained as the DDEA-SLN would have readily permeated through the lipoidal cell membrane but may not be completely available as free DDEA.


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)

Papp ×10−6 of LB, DDEA, DDEA-SLN, and TP drugs from Caco-2 mono culture.Notes: All values are expressed as mean ± SEM (*P<0.05, **P<0.005, ***P<0.0005). Papp represents the apparent permeability.Abbreviations: DDEA, diclofenac diethylamine; LB, lignocaine base; SLN, solid lipid nanoparticle; SEM, standard error of the mean; TP, transmucosal patch; ex, extracted.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-11-2901: Papp ×10−6 of LB, DDEA, DDEA-SLN, and TP drugs from Caco-2 mono culture.Notes: All values are expressed as mean ± SEM (*P<0.05, **P<0.005, ***P<0.0005). Papp represents the apparent permeability.Abbreviations: DDEA, diclofenac diethylamine; LB, lignocaine base; SLN, solid lipid nanoparticle; SEM, standard error of the mean; TP, transmucosal patch; ex, extracted.
Mentions: As shown in Figure 5, the permeability of LB present in TP was increased considerably when compared to the pure drug. This could be due to the presence of permeation enhancers LPG and clove oil, which loosen the lipid bilayer of the cell membrane and facilitate the movement of lipophilic drugs across the membrane. The permeability of DDEA was found to decrease when analyzed by filtering the collected media across 0.22 μm membrane. However, when the collected media were analyzed after extracting the DDEA from SLN the apparent permeability was found to be enhanced significantly. This phenomenon could be explained as the DDEA-SLN would have readily permeated through the lipoidal cell membrane but may not be completely available as free DDEA.

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