212
Views
22
CrossRef citations to date
0
Altmetric
Original Research

Transbuccal delivery of betahistine dihydrochloride from mucoadhesive tablets with a unidirectional drug flow: in vitro, ex vivo and in vivo evaluation

, , , &
Pages 4031-4045 | Published online: 14 Dec 2016

Figures & data

Table 1 Composition of BH.2HCl mucoadhesive buccal tablets

Figure 1 Diagrammatic sketch of mucoadhesive buccal tablet with a unidirectional drug flow.

Figure 1 Diagrammatic sketch of mucoadhesive buccal tablet with a unidirectional drug flow.

Table 2 Physicochemical parameters of the developed BH.2HCl mucoadhesive buccal tablets

Figure 2 Plot of % swelling vs time for BH.2HCl mucoadhesive buccal formulations (A) F1–F6 and (B) F7–F12.

Abbreviation: BH.2HCl, betahistine dihydrochloride.
Figure 2 Plot of % swelling vs time for BH.2HCl mucoadhesive buccal formulations (A) F1–F6 and (B) F7–F12.

Table 3 Mucoadhesive strength, force and residence time of BH.2HCl mucoadhesive buccal tablets

Table 4 In vivo mucoadhesion properties of BH.2HCl mucoadhesive buccal tablets

Figure 3 Release profile of BH.2HCl from different mucoadhesive buccal formulations: (A) F1–F6 and (B) F7–F12.

Abbreviation: BH.2HCl, betahistine dihydrochloride.
Figure 3 Release profile of BH.2HCl from different mucoadhesive buccal formulations: (A) F1–F6 and (B) F7–F12.

Table 5 Ex vivo permeation parameters of BH.2HCl mucoadhesive buccal tablets

Figure 4 Permeation profile of BH.2HCl from different mucoadhesive buccal formulations.

Abbreviations: BH.2HCl, betahistine dihydrochloride; SCH, sodium cholate hydrate; SDC, sodium deoxycholate.
Figure 4 Permeation profile of BH.2HCl from different mucoadhesive buccal formulations.

Figure 5 DSC thermograms of (A) pure BH.2HCl, (B) guar gum, (C) Na CMC, (D) HPMC K4M, (E) mannitol, (F) Aerosil 200, (G) magnesium stearate (H) SCH and (I) formulation F10 in addition to SCH.

Abbreviations: BH.2HCl, betahistine dihydrochloride; DSC, differential scanning calorimetry; HPMC K4M, hydroxypropyl methyl cellulose grade K4M; Na CMC, sodium carboxymethyl cellulose; SCH, sodium cholate hydrate.
Figure 5 DSC thermograms of (A) pure BH.2HCl, (B) guar gum, (C) Na CMC, (D) HPMC K4M, (E) mannitol, (F) Aerosil 200, (G) magnesium stearate (H) SCH and (I) formulation F10 in addition to SCH.

Figure 6 FTIR spectra of (A) pure BH.2HCl, (B) guar gum, (C) Na CMC, (D) HPMC K4M, (E) mannitol, (F) Aerosil 200, (G) magnesium stearate (H) SCH and (I) formulation F10 in addition to SCH.

Abbreviations: BH.2HCl, betahistine dihydrochloride; FTIR, fourier-transform infrared spectroscopy; HPMC K4M, hydroxypropyl methyl cellulose grade K4M; Na CMC, sodium carboxymethyl cellulose; SCH, sodium cholate hydrate.
Figure 6 FTIR spectra of (A) pure BH.2HCl, (B) guar gum, (C) Na CMC, (D) HPMC K4M, (E) mannitol, (F) Aerosil 200, (G) magnesium stearate (H) SCH and (I) formulation F10 in addition to SCH.

Figure 7 Chromatogram of BH.2HCl in the mobile phase at λmax 260 nm.

Abbreviations: BH.2HCl, betahistine dihydrochloride; min, minutes.
Figure 7 Chromatogram of BH.2HCl in the mobile phase at λmax 260 nm.

Table 6 Percentage of BH.2HCl remained in formulation F10 when stored at different temperatures (40°C and 60°C) for 12 weeks

Figure 8 Plot of log % BH.2HCl remained vs time after storage of the optimized buccal formulation for 12 weeks at 40°C and 60°C according to first-order kinetics.

Abbreviation: BH.2HCl, betahistine dihydrochloride.
Figure 8 Plot of log % BH.2HCl remained vs time after storage of the optimized buccal formulation for 12 weeks at 40°C and 60°C according to first-order kinetics.

Figure 9 BH.2HCl plasma concentrations following the administration of the optimized buccal formulation and oral tablets Betaserc® 24 mg.

Abbreviation: BH.2HCl, betahistine dihydrochloride.
Figure 9 BH.2HCl plasma concentrations following the administration of the optimized buccal formulation and oral tablets Betaserc® 24 mg.

Table 7 Mean pharmacokinetic parameters for the volunteers following administration of the optimized mucoadhesive buccal formulation and oral Betaserc® tablets