Penetration enhancers buccal

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

While there are limitations associated with the use of an in vitro permeability model for assessing the transport of compounds across the buccal mucosa, it can still be useful in assessing and comparing the permeability of compounds under different conditions, such as pH, temperature, and osmolarity, which provide valuable information on the mechanisms involved in drug transport. Additionally, the preliminary effects of potential chemical penetration enhancers or formulation excipients may be assessed, and these may provide a substantial rationale for subsequently assessing the effect of these agents in man. 

The buccal mucosa does serve as an alternative route for administering compounds systematically however, to ensure particular compounds are candidates for delivery across this biological tissue, preclinical screening is essential. While in vivo human permeability studies are ideal, due to their costs and associated issues, it is necessary to perform such screening in vitro. Assessment of compound permeability across porcine buccal mucosa has been widely used and can provide the preclinical biopharmaceutical scientist with much information relating to permeability, routes of transport, and effects of various chemical penetration enhancers. 

Coutel-Egros A, Maitani Y, Veillard M, Machida Y, Nagai T (1992) Combined effects of pH, cosolvent and penetration enhancers on the in vitro buccal absorption of propranolol through excised hamster cheek pouch. Int J Pharm 84 117-128... 

Gandhi R, Robinson J (1992) Mechanisms of penetration enhancement for trans-buccal delivery of salicylic acid. Int J Pharm 85 129-140... 

Nicolazzo JA, Reed BL, Finnin BC (2004b) Modification of buccal drug delivery following pretreatment with skin penetration enhancers. J Pharm Sci 93 ... 

Sandri G, Poggi P, Bonferoni MC, Rossi S, Ferrari F, and Caramella C (2006) Histological evaluation of buccal penetration enhancement properties of chitosan and trimethyl chitosan. J. Pharm. Pharmacol. 58 1327-1336. 

Sandri G, Rossi S, Ferrari F, Bonferoni MC, Zerrouk N, Caramella C (2004) Mucoadhesive and penetration enhancement properties of three different grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines and rat jejunum. J Pharm Pharmacol 56 1083-1090. 

Nicolazzo et al. [52] considered the use of the lipophilic skin penetration enhancers, octisalate and padimate (both used in sunscreens), in comparison to Azone on the buccal absorption of various drugs in vitro. They were found to have limited effect in enhancing the permeation of triamcinolone acetonide (although some increase in tissue uptake was proposed in some cases) relative to Azone, while reducing the penetration of estradiol and caffeine. One interesting report is that of the effect of capsaicin from capsicum, a commonly used food ingredient, which has been reported to enhance the permeability of sulfathiazole in human volunteers [53] presumably by a direct irritation effect on the mucosa. This raised an interesting issue of the effect of diet on oral mucosal permeability. 

Hoogstraate A.J., et al. 1997. Effects of the penetration enhancer glycodeoxycholate on the lipid integrity in porcine buccal epithelium in-vitro. Eur J Pharm Sci 5 189. 

Sandri, G., et al. 2004. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci 21 35. 

This approach consists of transiently increasing the permeability characteristics of the cornea by appropriate substances, known as penetration enhancers or absorption promoters. It bears a strict analogy to techniques aimed at facilitating drug penetration through the skin and other epithelia such as the buccal, nasal, intestinal, or rectal. 

The nonperoral mucosal delivery routes such as buccal, nasal, and vaginal sites offer barriers to drug molecules similar to that of the peroral route. Drugs delivered via these routes have to be small (<300 Da), lipophilic in nature, and with low dosage regimen requirements. The different approaches used to deliver drugs across these mucosae include the use of enzyme inhibitors, penetration enhancers, bioadhesive patches, prodrugs, liposomes, and solubility modifiers.96,106,130... 

As discussed above, patient acceptability and comfort requirements dictate that the surface area of a buccal patch is not greater than 15 cm2. The limited surface area available for absorption often means that a penetration enhancer is necessary to ensure ... 

Locally irritating or sensitizing dmgs must be used with caution in this route. Nasal epithelia, and in particular the cilia, are highly sensitive and fragile. This contrasts with, for example, the buccal epithelium which is much more robust and less prone to irritation. The fragility of the tissue also means that this route is particularly sensitive to the adverse effects of penetration enhancers. Damage to the epithelium could result in compromised mucocilary clearance which is associated with respiratory disease. 

There are a number of excellent reviews on the requirements for enhancing drug permeability across lipophilic biological barriers, with particular reference to the importance of the lipophilic properties of formula-tions. A listing of some penetration enhancing lipids can be found in Table 3. Administration sites include buccal, oral, nasal, ocular, transdermal, rectal, and pulmonary. 

This luteinizing hormone-releasing hormone has been used in the treatment of endometriosis and hormone-dependent tumors. Modes of administration have included injections, nasal sprays and subcutaneous implantations. One study, conducted in pigs, demonstrated the value of glycodeoxycholate (a penetration enhancer) in improving the bioavailability of buserelin by up to five-fold after buccal delivery. ... 

Movement of penetrants across the mucous membranes is by diffusion. At steady state, the amount of a substance crossing the tissue per unit of time is constant and the permeability coefficients are not influenced by the concentration of the solutions or the direction of nonelectrolyte transfer. As in the epidermis of the skin, the pathways of permeation through the epithelial barriers are intercellular rather than intracellular. The permeability can be enhanced by the use surfactants such as sodium lauryl sulfate (a cationic surfactant). An unsaturated fatty acid, oleic acid, in a propylene glycol vehicle can act as a penetration enhancer for diffusion of propranolol through the porcine buccal mucosa in vitro. Delivery of biopharmaceuticals across mucosal surfaces may offer several advantages over injection techniqnes, which include the following ... 

Sandri, G., S. Rossi, F. Ferrari, M. C. Bonferoni, C. Muzzarelh, and C. Caramella. 2004. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. European Journal of Pharmaceutical Sciences 21 (2-3) 351-359. 

Sandri, G., Rossi, S., Bonferoni, M.C., Ferrari, F., Zambito, Y., Di Colo, G., Caramella, C. Buccal penetration enhancement properties of N-trimethyl chitosan influence of quaterni-zation degree on absorption of a high molecular weight molecule. Int. J. Pharm. 297, 146 (2005)... 

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