Mucoadhesive buccal tablet

A typical basic formulation of a mucoadhesive buccal tablet is given in Table 182. In this case the adhesive effect of copovidone was much higher than the adhesion of povidone K 30 or povidone K 90. 

Table 182. Basic formulations of a mucoadhesive buccal tablet...

Buccal testosterone tablets provide sustained release of testosterone and also bypass first-pass metabolism in the liver. Small-scale work with a bioadhesive buccal tablet of testosterone has shown that adequate serum concentrations can be obtained and that the buccal tablet (administered twice daily) is well tolerated (102). Other work has confirmed that twice-daily buccal application is optimal to maintain therapeutic serum concentrations of testosterone and its metabolites (103-105) however, it appears that about one patient in six initially has a degree of oral discomfort from the presence of the mucoadhesive tablet, although this fades after a few days and does not seriously affect compliance. Common adverse effects of buccal testosterone include gum irritation, pain, and tenderness, and edema (106) and headache (107). 

Recently a study investigated different types of mucoadhesive polymers for buccal tablet formation [80]. The polymers used were Carbopol (CP934 and CP940), PCP, sodium... 

Nafee, N.A., et al. 2004. Mucoadhesive delivery systems. I. Evaluation of mucoadhesive polymers for buccal tablet formulation. Drug Dev Ind Pharm 30 985. 

In the 1980s, Machida and Nagai evaluated spray dosage forms based on hydroxypropyl cellulose (HPC) for the delivery of beclomethasone to treat recurrent and multiple apthae. Previously a double-layered tablet of HPC and Carbopol 934P was introduced in the market for the treatment of apthous stomatitis. " Bouckaert, Lefebvre, and Remon " tested buccal tablets of miconazole based on modified starch-polyacrylic acid mixtures. Although these tablets showed different mucoadhesion properties in vitro, no significant differences in the salivary content of miconazole could be observed in human volunteers. 

Examples of marketed mucoadhesive formulations are Attach buccal tablets (triamcinolone acetonide), Susadrin sublingual tablets (nitroglycerin Forest Laboratories, NY), and Buccastem buccal tablets (prochlorperazine maleate Reckitt and Colman, England). 

The size of the delivery system varies with the type of formulation, i.e., a buccal tablet may be approximately 5-8 mm in diameter, whereas a flexible buccal patch may be as large as 10-15 cm in area. Mucoadhesive buccal patches with a surface area of 1-3 cm are most acceptable. It has been estimated that the total amount of drug that can be delivered across the buccal mucosa from a 2-cm system in 1 day is approximately 10-20 mg.f The shape of the delivery system may also vary, although for buccal drug administration, an ellipsoid shape appears to be most acceptable. The thickness of the delivery device is usually restricted to only a few millimeters. The location of the delivery device also needs to be considered. A mucoadhesive retentive system is preferred over a conventional dosage form. A bioadhesive buccal patch would appear to be the most appropriate delivery system because of its flexibility and the area of the buccal mucosa available for its application. The maximal duration of buccal drug retention and absorption is approximately 4-6 h because food and/or liquid intake may require removal of the delivery device. 

Alur, H.H. Beal, J.D. Father, S.I. Mitra, A.K. Johnston, T.P. Evaluation of a novel, natural oligosaccharide gum as a sustained-release and mucoadhesive component of calcitonin buccal tablets. J. Pharm. Sci. 1999, 88, 1313-1319. 

Teng, C.L.D. Groves, M.J. The effect of compactional pressure on urease activity. Pharm. Res. 1988, 5, 776-780. Alur, H.H. Paher, S.I. Mitra, A.K. Johnston, T.P. Transmucosal sustained delivery of chlorpheniramine maleate in rabbits using a novel, natural mucoadhesive gum as an excipient in buccal tablets. Int. J. Pharm. 1999,188, 1-10. Kondo, S. Sugimoto, I. Moment analysis of intravenous, intraduodenal, buccal, rectal, and percutaneous nifedipine in rats. J. Pharmacobio. Dyn. 1987, 10, 462 69. Yamamoto, A. Hayakawa, E. Lee, V.H. Insulin and proinsulin proteolysis in mucosal homogenates of the albino rabbit implications in peptide delivery from nonoral routes. Life Sci. 1990, 26, 2465-2474. 

Povidone reduces the adherence of oral bacteria to tooth enamel and therefore it could be used in buccal preparations e.g. mouthwash solution as microbial antiadherent agent [589]. It also can be used as mucoadhesive for buccal coats of verapamil [612] or for bioadhesive buccal tablets of nicotine [639,641]. 

Kotagale, N. Patel, C. Parkhe, A. Khandelwal, H. Taksande, J. Umekar, M. Carbopol 934-sodium alginate-gelatin mucoadhesive ondansetron tablets for buccal delivery Effect of PH modifiers. Indian J. Pharm. Sci. 2010, 72 (4), 471 79. 

The strength of mucoadhesion of the tablets was quantified based on the tensile force required to break the adhesive bond between a model membrane, i.e., porcine buccal mucosa and the test pol5mier. The study revealed that locust bean gum and chitosan in a weight ratio of 2 3 not only releases the drug unidirectionally from the dosage form, but also results in buccal tablets which are sufficiently mucoadhesive for clinical applications (34). 

Due to its mucoadhesive and sustained-release properties, hakea gum (HG), obtained from the shrub Hakea gibbosa (Sm.) Cav. (Proteaceae), is used for the formulation of some buccal tablets containing chlorpheniramine maleate [242,243] or calcitonin [243]. Flat-faced Cutina-coated core tablets containing either 22/32 mg of HG, 25/40 mg of chlorpheniramine maleate and sodium bicarbonate/tartaric acid (1 1.5 molar ratio) were obtained by direct compression technique [243]. Also, an improved trans-buccal delivery system for therapeutic polypeptides obtained using direct compression technique supposes flat-faced Cutina-coated core tablets containing either 12/32 mg of HG and 40 pg (200 lU) of salmon calcitonin [244]. 

Alur HH, Becd JD, Father SI, Mitra AK, Johnston TP. Evcduation of a novel, naturcd oligosaccharide gum cis a sustcuned-release and mucoadhesive component of Ccddtonin buccal tablets. J Pharm Sci. 88 (12) 1313-1319,1999. 

An alternative to the oral route is the buccal mucoadhesive system. The Striant buccal system adheres to the inside of the mouth and the testosterone is absorbed through the oral mucosa and delivered to the systemic circulation. There is no first-pass effect, as the liver is bypassed by this route of administration. Patients apply a 30-mg tablet to the upper gum twice daily. The cost is similar to that of the patch or gel. Side effects unique to this dosage form include oral irritation, bitter taste, and gum edema. 

Sustained adhesion of the dosage form (tablet, patch) to the mucosa is an important first step to successful buccal delivery. The mucus plays an important role during this mucoadhe-sive process by buccal drug delivery systems. The interaction between the mucus and mucoadhesive polymers generally used in most dosage forms can be explained by theories summarized in Table 9.1. 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

For local but also systemic delivery, the oromucosal route might be suitable if safety is established. Mucoadhesive preparations, especially films, semi-solids and liquids, might be of interest if they do not interfere with suction and frequent feeding. Nevertheless, one of the major issues remains the taste of the preparation and the willingness as well as the ability of the child to retain buccal or sublingual tablets in the mouth, thus ensuring that sufficient absorption takes place. 

Hydroxypropyl cellulose (HPC) is a non-ionic water-soluble and pH insensitive cellulose ether. It can be used as thickening agent, tablet binder and modified release and film coating polymer. Buccal delivery formulations containing HPC and polyacrylic acid are used for many years and is used for mucoadhesive delivery systems for several drugs. 

Buccal mucoadhesive tablets are mostly intended for systemic use, but adhesive tablets and semisolid forms can also be used to obtain a local effect. 

An example is a mucoadhesive tablet with miconazole. With this dosage form higher saliva concentrations are obtained compared to an oral gel, whilst no miconazole is detectable in blood plasma [9]. Other examples are buccal films, in use for the treatment of herpes labialis [10]. 

Other modern research has highlighted the importance of CG for different drug delivery systems, as follows CG and chitosan combinations (2 3,3 2, and 4 1) as a carriers for buccal drug delivery of 10 mg propranolol hydrochloride mucoadhesive tablets coated on one face with 5% (w/v) ethyl cellulose or formulated using a direct compression technique [226] enhancement of solubility, dissolution rate and bioavailability of poorly water-soluble drug lovastatin using modified CG (by heating) and solid dispersion techniques [227] formulation and evaluation of nimesulide orodispersible tablets... 

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