Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: Formulation and in vitro/in vivo evaluation
Graphical abstract
Introduction
The buccal mucosa, lining of the oral cavity, is an attractive site for drug administration as it is highly vascular, easily accessible and suitable for retentive dosage forms administration. The buccal transmucosal drug delivery claims advantage over per-oral administration as it bypasses the first-pass effect and avoids the presystemic drug elimination within the gastrointestinal tract (Patel et al., 2012, Salamat-Miller et al., 2005, Sudhakar et al., 2006). Buccal mucoadhesive dosage forms include: tablets (Boyapally et al., 2010, Cilurzo et al., 2010), films (Rossi et al., 2003), patches (Nafee et al., 2003, Reddy et al., 2013, Shidhaye et al., 2008), gels (Perioli et al., 2008) and sponges (Portero et al., 2007). Dosage forms designed for buccal drug delivery should possess good bioadhesive properties, high drug loading capacity and cause no irritation. In addition, it should have controlled drug release properties preferably in a unidirectional way toward the mucosa and to be an erodible system so that the dosage form removal at the end of the desired dosing interval is not required (Salamat-Miller et al., 2005). Buccal tablets are the most common dosage forms for buccal drug delivery. Buccal tablets are usually prepared by direct compression and intended to dissolve or erode slowly. Buccal tablets may be prepared in different forms including, monolithic, bilayered and cup and core buccal tablets to achieve unidirectional drug release (Salamat-Miller et al., 2005).
Many mucoadhesive polymers are employed in the preparation of the buccal mucoadhesive systems: anionic such as carbopol (CP), sodium alginate (SALG) and sodium carboxymethyl cellulose (SCMC); cationic such as chitosan; and non-ionic polymers such as hydroxypropyl methylcellulose (HPMC) and guar gum (GG) (Andrews et al., 2009).
Buspirone HCl (BH) is an anxiolytic drug acting by modulating the serotonergic system (Shumilov and Touitou, 2010). It is used in the treatment of generalized anxiety disorder and for anxiety symptoms in depression (Nash and Nutt, 2005). BH undergoes extensive first-pass metabolism leading to very low oral bioavailability (4%) (Gannu et al., 2009, Moffat et al., 2011). The short and variable elimination half-life of BH (mean of 2.4 h) (Moffat et al., 2011, Sakr and Andheria, 2001), its low bioavailability and low molecular weight (422) (Moffat et al., 2011) recommend it a good candidate for sustained release buccal dosage forms.
In vitro/in vivo correlation (IVIVC) is the relation between the in vitro dissolution data and the in vivo input rate. A good IVIVC can be used as a surrogate for further bioequivalence studies and to predict in vivo results based on in vitro data. Four levels of IVIVC (level A, B, C and multiple level C) have been described in the FDA guidance. Of these levels, level A IVIVC is considered the most informative, representing a point to point relationship between the in vitro dissolution rate and the in vivo absorption rate (Shah et al., 2009, Uppoor, 2001).
In the present study, BH mucoadhesive buccal tablets of both matrix and cup and core designs were developed using: CP 934P, HPMC K4M, SALG, SCMC and GG. The effect of these polymers on BH release profile and on the mucoadhesion properties of the tablets was studied. The compatibility between BH and the tablet excipients was studied using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The buccal tablets were evaluated in term of content uniformity, weight variation, thickness, diameter, hardness, friability, surface pH, swelling index, mucoadhesion strength, ex vivo mucoadhesion time and in vitro drug release. The selected formula was further evaluated for its in vivo performance in four healthy human volunteers compared to commercially available BH tablet (Buspar®, 15 mg BH, Glaxo-Smith Kline Co., Cairo, Egypt). Level A IVIVC was conducted between the in vitro dissolution data and the in vivo absorption data of the selected formula.
Section snippets
Materials
Buspirone hydrochloride (BH) was kindly supplied by Glaxo-Smith Kline Co. (Cairo, Egypt). Carbopol 934P was obtained from Goodrich Chemical Co. (OH, USA). Hydroxypropyl methyl cellulose K4M was purchased from Colorcon (Midland, USA). Sodium alginate (viscosity = 14,000 cps) was purchased from MP chemicals (France). Ketorolac (internal standard), sodium carboxymethyl cellulose, guar gum, ethyl cellulose 100 cps (Ethocel), formic acid and acetonitrile (HPLC grade) were purchased from Sigma-Aldrich
Solubility of BH in SSF
The mean equilibrium solubility of BH in SSF (pH 6.8) was found to be 3.73 ± 0.13 mg/ml. Such high solubility proved that the volume of dissolution medium used in the in vitro study ensured sink condition for the doses of BH used to load the formulations.
DSC
Pure BH exhibited an endothermic peak of 203.23 °C corresponding to its melting point (Al-Zoubi et al., 2008). The DSC peak of BH was preserved in its physical mixtures with each of the aforementioned excipients indicating that there was no
Conclusion
BH mucoadhesive buccal tablets prepared and showed acceptable physical properties. The analysis of the factorial design revealed that none of the prepared BH buccal matrix tablets fulfilled the desired release pattern in combination with the desired mucoadhesion time (8 h). Further optimization through preparation of BH cup and core buccal tablets was performed. Mucoadhesive cup C8 had the required optimum mucoadhesion time (8 h) and highest mucoadhesion force (1.2 N) so it was used in the
References (62)
- et al.
Sustained-release of buspirone HCl by co spray-drying with aqueous polymeric dispersions
Eur. J. Pharm. Biopharm.
(2008) - et al.
Mucoadhesive polymeric platforms for controlled drug delivery
Eur. J. Pharm. Biopharm.
(2009) - et al.
Controlled release from directly compressible theophylline buccal tablets
Colloids Surf. B: Biointerfaces
(2010) - et al.
Influence of the viscosity grade and the particle size of HPMC on metronidazole release from matrix tablets
Eur. J. Pharm. Biopharm.
(1997) - et al.
Quantification of a cytochrome P450 3A4 substrate, buspirone, in human plasma by liquid chromatography–tandem mass spectrometry
J. Chromatogr. B
(2006) - et al.
A new mucoadhesive dosage form for the management of oral lichen planus: formulation study and clinical study
Eur. J. Pharm. Biopharm.
(2010) - et al.
Matrices containing NaCMC and HPMC 1. Dissolution performance characterization
Int. J. Pharm.
(2007) - et al.
Development of high performance liquid chromatography method for buspirone in rabbit serum: application to pharmacokinetic study
Anal. Chim. Acta
(2009) Mechanism of Sustained-Action Medication. Theoretical Analysis of Rate of Release of Solid Drugs Dispersed in Solid Matrices
J. Pharm. Sci.
(1963)- et al.
Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation
Int. J. Pharm.
(2004)
Design and evaluation of controlled drug delivery system of buspirone using inorganic layered clay mineral
Micropor. Mesopor. Mater.
Mechanisms of solute release from porous hydrophilic polymers
Int. J. Pharm.
Effect of HPMC and carbopol on the release and floating properties of gastric floating drug delivery system using factorial design
Int. J. Pharm.
Evaluation of sodium alginate as drug release modifier in matrix tablets
Int. J. Pharm.
Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of ageing
Int. J. Pharm.
Development and evaluation of a biphasic buccal adhesive tablet for nicotine replacement therapy
Int. J. Pharm.
Modeling the oral cavity: in vitro and in vivo evaluations of buccal drug delivery systems
J. Control. Release
A simple equation for the description of solute release. III. Coupling of diffusion and relaxation
Int. J. Pharm.
FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration
Int. J. Pharm.
Novel mucoadhesive buccal formulation containing metronidazole for the treatment of periodontal disease
J. Control. Release
Rheological and functional characterization of new antiinflammatory delivery systems designed for buccal administration
Int. J. Pharm.
Development of chitosan sponges for buccal administration of insulin
Carbohydr. Polym.
A simple equation for description of solute release II. Fickian and anomalous release from swellable devices
J. Control. Release
The use of mucoadhesive polymers in buccal drug delivery
Adv. Drug Deliv. Rev.
Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC
J. Control. Release
Buspirone transdermal administration for menopausal syndromes, in vitro and in animal model studies
Int. J. Pharm.
Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC)
Adv. Drug Deliv. Rev.
Correlation of in vitro release and in vivo absorption characteristics of rifampicin from ethylcellulose coated nonpareil beads
Int. J. Pharm.
Buccal bioadhesive drug delivery—a promising option for orally less efficient drugs
J. Control. Release
Effect of anionic polymers on the release of propranolol hydrochloride from matrix tablets
Eur. J. Pharm. Biopharm.
Preparation, characterization, and evaluation of miconazole–cyclodextrin complexes for improved oral and topical delivery
J. Pharm. Sci.
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