Several approaches have been investigated to improve absorption through buccal mucosa by addition of permeation enhancers is one of the approaches. Substances that facilitate the permeation through buccal mucosa are referred as permeation enhancers. Incorporation of permeation enhancers improves the delivery of drug via buccal membrane, which could reduce barrier properties of the buccal epithelium (Schipper et al., 1997Schipper NG, Olsson S, Hoogstraate JA, deBoer AG, Varum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs 2: Mechanism of absorption enhancement. Pharm Res . 1997;14:923-929.). Compared to the intestinal, rectal and nasal mucosa, oral mucosa is highly vascularized with reduced enzyme activity, less sensitive to damage and irritation. The oral mucosa consists of sublingual mucosa and buccal mucosa for delivery of drugs with high permeability for acute diseases and prolonged for chronic diseases respectively (Kumar et al., 2014Kumar GP, Geethika R, Anusha T, Jaweria S, Prathyusha G. The potential of statins for buccal delivery. J Mol Pharm Org Process Res. 2014;2(1):111.). For oral mucosal drug delivery system, the mucosa consists of great surface area which is usually rich in blood supply. To provides for rapid drug transport to the systemic circulation through the internal jugular bypasses drugs from the hepatic first-pass metabolism, avoiding drug degradation in acidic stomach environment and enhances drug bioavailability (Rojanasakul et al., 1992Rojanasakul Y, Wang LM, Bhat M, Glover DD, Malanga CJ, Ma JKH. The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit. Pharm Res. 1992;9:1029-1034.; Zhang et al., 2002Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002;41:9:661-80.; Harris, Robinson, 1992Harris D, Robinson JR. Drug delivery via the mucous membranes of the oral cavity. J Pharm Sci. 1992;81:1-10.; Palem et al., 2016bPalem CR, Reddy ND, Satyanarayana G, Varsha BP. Development and optimization of Atorvastatin calcium- cyclodextrin inclusion complexed oral disintegrating tablets for enhancement of solubility, dissolution, pharmacokinetic and pharmacodynamic activity by central composite design. Int J Pharm Sci Nanotech . 2016;9(2):1-11.; Jaipal et al., 2016Jaipal A, Pandey MM, Charde SY, Sadhu N, Srinivas A, Prasad RG. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies. Drug Deliv. 2016;23(2): 452-458.).
The porcine buccal mucosa was collected from the local slaughter house and was immediately transported to the laboratory in cold normal saline solution. The buccal mucosa was carefully separated from fat and muscles using a small sharp blade. The buccal mucosal epithelium was used within two hours. The in-vitro buccal drug permeation study was performed using a Franz diffusion cell at 37 ºC ± 0.5 ºC. The buccal mucosa was fixed between the donor and receptor compartments. The receiver chamber (50 ml capacity) was filled with phosphate buffer pH 6.8. The buccal mucosa was allowed to stabilize for a period of 30 min. The buccal tablet was placed in donor chamber and 1mL of buffer solution (pH 6.8) was added and the tablet was placed with the core facing the mucosa, and the compartments were clamped together. The hydrodynamics in the receiving compartment was maintained by continuous stirring with a magnetic bead at a uniform speed throughout the study (Brahmankar, Jaiswal, 2003Brahmankar DM, Jaiswal SB. Biopharmaceutics and pharmacokinetics a treatise. 1. Ed. Delhi: Vallabh Prakashan 2003; p.230-272.; Satyabrata, Murthy, Padhy, 2010Satyabrata B, Murthy K V R, Padhy S. Design and in vitro evaluation of muco-adhesive buccal tablet of Perindopril prepared by Sintering technique. Pharm Clin Res. 2010;3(4): 4-10.; Himabindu et al., 2018Himabindu P, Narendar D, Krishna Mohan C, Nagaraju B. Transmucosal delivery of duloxetine hydrochloride for prolonged release: preparation, in vitro, ex vivo Characterization and in vitro-ex vivo correlation. Int J Pharm Sci Nanotech . 2018;11(5):4249-4258.). Samples were collected at predetermined time intervals. The amount of drug permeated through the buccal mucosa was then determined by UV spectrophotometer at 260 nm. 2b1af7f3a8