• SUMANJALI DODLA Department of Pharmaceutics, KLR Pharmacy College, Paloncha, Khammam, Andhra Pradesh, India,
  • SELLAPPAN VELMURUGAN Department of Pharmaceutics, KLR Pharmacy College, Paloncha, Khammam, Andhra Pradesh, India


Penetration enhancers, buccal mucosa, Drug delivery system, Intercellular lipids


Over the last decade, there has been a particular interest in delivering drugs in buccal mucosa and aiming to increase bioavailability of varied controlled drug delivery systems (CDDS), mucoadhesion (the capability of a object to adhere to mucous membranes) occupies a unique position. Buccal administration of API provides a convenient route of administration for both systemic and local actions. It provides direct entry into the systemic circulation thus avoiding the hepatic first-pass effect and degradation in the gastrointestinal tract. However permeability of oral mucosa is limiting factor which relatively low compared to intestinal mucosa and the skin. When permeability differences between various organs of the oral region are taken into consideration, buccal membrane found to be more permeable. In order to deliver wider classes of drugs across the buccal mucosa, the barrier potential of mucosa must be reduced. This requisite has forced the study of buccal penetration enhancers that will overcome the permeability barrier of the buccal mucosa. Numerous compounds have been evaluated for penetration enhancing activity, including bile salts, surfactants, fatty acids and derivatives, ethanol, cyclodextrins and chitosan etc. The purpose of this review is to identify the structural and chemical nature of the permeability barrier the buccal mucosa, to clarify the mechanisms of action of buccal penetration enhancers.


Author Biography

SELLAPPAN VELMURUGAN, Department of Pharmaceutics, KLR Pharmacy College, Paloncha, Khammam, Andhra Pradesh, India



John D. Smart .The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev 2005; 57: 1556– 1568.

Kishore grandhi, M. Muthukumaran, B. Krishna Moorthy. Recent advances in mucoadhesive hydrogels in drug delivery system. Int. J. of Pharm. & Research Sci 2012; 1(5): 355-367.

Khanna R, Agrawal SP. Mucoadhesive buccal drug delivery: a potential alternative to conventional therapy. Indian Journal of Pharmaceutical Science 1998; 60(1):1-11.

Jinsong hao and Paul W. S. Heng. Buccal delivery systems. Drug development and industrial pharmacy 2003;29(8): 821–832.

Yajaman Sudhakar, Ketousetuo Kuotsu, A.K. Bandyopadhyay .Buccal bioadhesive drug delivery - A promising option for orally less efficient drugs. Journal of Controlled Release 2006; 114:15–40.

Surender Verma, Mahima Kaul, Aruna Rawat and Sapna Saini . An Overview on Buccal Drug Delivery System. International Journal of Pharmaceutical Sciences and Research 2011; 2(6):1303-132.

Jonwal Nitin,Mane Pallavi, Sharma Kapil Kumar . Buccoadhesive drug delivery - a potential route of drug administration. International Journal of Pharmaceutical & Biological Archives 2010; 1(1): 11-23.

Pragati Shakya , N.V. Satheesh Madhav Ashok K. Shakya , Kuldeep Singh. Palatal mucosa as a route for systemic drug delivery: A review. Journal of Controlled Release 2011; 151:2–9.

Rossi Silvia, Sandri, and Caramella.Buccal drug delivery: A challenge already won? Drug Discov Today Technol 2005; 2(1): 59-65.

C.A. Squier, P. W. Wertz. Structure and function of the oral mucosa and implications for drug delivery, in: M. J. Rathbone (Ed.), Oral Mucosal Drug Delivery, Marcel Dekker, Inc., New York 1996; 74: 1-26.

I.D. Consuelo, Y. Jacques, G. Pizzolato, R.H. Guy, F. Falson. Comparison of the lipid composition of porcine buccal and esophageal permeability barriers. Arch. Oral Biol 2005; 50: 981-987.

S.P. Humphrey, R.T. Williamson. A review of saliva: normal composition, flow and function. J. Prosthet. Den 2001; 85: 162-169.

Dhaval A. Patel et al: Buccal Mucosa as A Route for Systemic Drug Delivery: A Review.Int. J. Drug Dev. & Res 2012; 4 (2): 99-116.

Janet A.J. Hoogstraate and Philip W. Wertz. Drug delivery via the buccal mucosa. Research focus 2008; 7:309-316.

Gills onchel. Formulation of oral mucosal drug delivery systems for systemic delivery of bioactive materials. Adved drug delivery systems 1998; 13:75-87.

A.H. Shojaei. Buccal mucosa as a route for systemic drug delivery: a review. J. Pharm. Pharm. Sci 1998; 1(1):15–30.

Galey, W.R., Lonsdale, H.K and Nacht, S.The in vitro permeability of skin and buccal mucosa to selected drugs and tritiated water. J. Invest. Dermat 1976; 67:713-717.

A.J. Hoogstraate, C. Cullander, J.F. Nagelkerke, S. Senel, J.C. Verhoef, H.E. Junginger, H.E. Bodde. Diffusion rates and transport pathways of fluorescein isothiocyanate (FITC)- labeled model compounds through buccal epithelium. Pharm. Res 1994; 11: 83– 89.

Magnusson, B. M., Walters, K. A., Roberts, M. S.Veterinary drug delivery: potential for skin penetration enhancement. Advanced Drug Delivery Reviews 2001; 50: 205 –227.

Vanessa Hearnden, Vidya Sankar, Katrusha Hull, Danica Vidovic Juras, Martin Greenberg etl.A New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Advanced Drug Delivery Reviews 2012; 64:16–28.

Joseph A. Nicolazzo, Barry L. Reed, Barrie C. Finnin. Buccal penetration enhancers-How do they really work? Journal of Controlled Release 2005; 105:1-15.

Steward, A., Bayley, D.L., and Howes, C. The effect of enhancers on the buccal absorption of hybrid (BDBB) alpha-interferom. Int. J. Pharm 1994; 104:145- 149.

S. Senel, A.A. Hıncal .Drug permeation enhancement via buccal route: possibilities and limitations. Journal of Controlled Release 2001; 72: 133-144.

Chinna Reddy P,Chaitanya K.S.C., Madhusudan Rao Y.A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. DARU 2011; 19(6):385-403.

Katrin Moser, Katrin Kriwet, Aarti Naik, Yogeshvar N Kalia, Richard H Guy. Passive skin permeation enhancement and its qualification invitro. European journal of pharmaceutics and Biopharmaceutics 2001; 52:103-112.

Y.Vamshi Vishnu,K.Chandrasekhar,G. Ramesh and Y.Madhusudan Rao.Development of Mucoadhesive Patches for Buccal Administration of Carvedilol. Current Drug Delivery 2007; 4: 27-39.

Noha Adel Nafee, Nabila Ahmed Boraie, Fatma Ahmed Ismail, Lobna Mohamed Mortada. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride .Acta Pharm 2003; 53: 199–212.

S. Singh, S. Jain, M. S. Muthu, S. Tiwari, and R. Tilak Stephen A. Preparation and Evaluation of Buccal Bioadhesive Films Containing Clotrimazole .AAPS PharmSciTech 2008;9(2):660-7.

Bharath Kumar.V, Ashok kumar.A, Sudheer.B, Suresh Kumar.K, Srinivasa Rao.V, Kirtinidhi.K, Hitesh R Patel and Putta Rajesh Kumar. Formulation design, in vitro evaluation and stability studies on mucoadhesive buccal films of anti-anginal calcium channel blocker. Journal of Applied Pharmaceutical Science 2011; 1(6): 136-142.

Semalty A, Semalty M, Nautiyal U .Formulation and Evaluation of Enaprail Maleate buccal films. Indian J Pharm Sci 2010; 72(5):571-5.

Y.indira muzub.Formulation and evaluation of glibenclamide mucoadhesive buccal films. Int J Pharma Investig 2012; 2(1):26-33.

Semalty M, Semalty A, Kumar G, Juyal V. Development of Mucoadhesive Buccal Films of Glipizide. International Journal of Pharmaceutical Sciences and Nanotechnology 2008; 1(2):185-190.

J. Thimmasetty, C. Suresh Babu and N. Udupa .Preparation and evaluation of buccal dosage forms of insulin, Source Pharmag 1996.

Marina Koland, R.N. Charyulu and Prabhakara Prabhu.Design and Characterization Mucoadhesive films of Losartan Potassium for Buccal delivery.Indian J.Pharm. Educ. Res 2010; 44(4):315-23.

M. Alagusundaram1, B. Chengaiah1, S. Ramkanth1, S. Angala Parameswari1 C. Madhu Sudhana Chetty and D. Dhachinamoorthi. Formulation and evaluation of mucoadhesivebuccal films of ranitidine. International Journal of PharmTech Research 2009; 3(1): 557-563.

Rama Bukka, Kalyani Prakasam, Chintan D Patel.Preparation and Evaluation of Intraoral Drug Delivery System for Rasagiline mesylate.International Journal of Pharmaceutical Sciences and Drug Research 2010; 2(4): 294-301.

Avinash singh, Pinkesh patel, Rama bukka, Jimmy patel .Preparation and Evaluation of buccal formulation for Triamcinolone.International Journal of Current Pharmaceutical Research 2011; 3(3):74-80.

Parikh Bhavik ,Anjankumar .Design and evaluation of buccal patches of valsartan. Journal of pharmaceutics and cosmetology 2011;21(3) :241-248.

Biswajit Basu1, Kevin Garal1, Thimmasetty J. Formulation and Evaluation of Pimozide Buccal Mucoadhesive Patches. International Journal of Pharmaceutical Sciences and Nanotechnology 2010; 2(4):739-748.

Subash Pillai, Saraswathi.R, Dilip.C. Design and evaluation of buccal films of isoxsuprine hydrochloride.Research Journal of Pharmaceutical, Biological and Chemical Sciences 2010; 1(2): 160-167.

Bazigha k abdul rasool1, saeed a. khan. In vitro evaluation of miconazole mucoadhesive buccal films. International journal of apllied pharmaceutics 2010; 2(4):739-748.

Manish kumar, Garima garg, Pushpendra kumar, g.t. kulkarni, Arun kumar. Design and in vitro evaluation of mucoadhesive buccal films containing famotidine. International Journal of Pharmacy and Pharmaceutical Sciences 2010; 2(3): 86-90.

Aarifkhan. M. pathan, Madhuri a. channawar, Bharti. v. bakde, Dr. anil v. Development and invitro evaluation of Salbutamol Sulphate mucoadhesive buccal patches ,Inter national Journal of Pharmacy and Pharmaceutical Sciences 2011; 3(2):39-44.

Satish darani and Shayada. Development and Invitro evaluation of Ondersteron hydrochloride mucoadhesive buccal patches. International Journal of Pharmaceutical Sciences and nanotechnology 2010; 3(1):860-866.

Magdy I. Mohamed,Mohamed Haider, Muaadh A. Mohamed Ali .Buccal Mucoadhesive Films Containing Antihypertensive Drug: In vitro/in vivo Evaluation. J. Chem. Pharm. Res 2011; 3(6):665-686.

Amit khairnar, Parridhi jain1, Dheeraj baviskar and Dinesh jain1.Developmement of mucoadhesive buccal patch containing Aceclofenac: in vitro evaluations.International journal of pharmtech research 2009; 1(4): 978-981.

Mishra A, Ramteke S. Formulation and evaluation of mucoadhesive buccal film of flurbiprofen. International journal of pharmtech research 2011; 3(3):1825-1830.

Satyabrata B., Ellaiah P., Choudhury R., Murthy K.V.R., Bibhutibhusan P., and Kumar M.S. Design and evaluation of methotrexate buccal mucoadhesive patches. Inter. J. Pharm. Biomed. Sci 2010; 1(2): 31-36.

Rao R.N.G., and Suryakar V.B. Formulation and evaluation of motelukast sodium mucoadhesive buccal patches for chronic asthma attacks. Inter. J. Pharm. and Bio. Sci 2010; 1 (2): 1-14.

Manasa B., Gudas G.K., Sravanthi N., Madhuri R.A., Lavanya Y., and Pranitha C. Formulation and evaluation of mucoadhesive buccal patches of resperidone. J Chem. and Pharm. Res 2010; 2(4): 866-872.

Patel K.V., Patel N.D, Dodiya H.D, Shelat P.K. Buccal Bioadhesive Drug Delivery System: An Overview International Journal of Pharmaceutical & Biological Archives 2011; 2(2): 600-609.

V.H.M. Deneer, G.B. Drese, P.E.H. Roemele, J.C. Verhoef, L. Lie-A-Huen, J.H. Kingma, J.R.B.J. Brouwers, H.E. Junginger,.Buccal transport of flecainide and sotalol: effect of a bile salt and ionization state. Int. J. Pharm 2002; 241: 127–134.

S. Senel, Y. Capan, M.F. Sargon, G. Ikinci, D. Solpan, O. Gu¨ven, H.E. Bodde, A.A. Hincal. Enhancement of transbuccal permeation of morphine sulfate by sodium glycodeoxycholate in vitro. J. Control. Release 1997; 45: 153– 162.

S. Senel, D. Duchene, A.A. Hincal, Y. Capan, G. Ponchel. In vitro studies on enhancing effect of sodium glycocholate on transbuccal permeation of morphine hydrochloride. J. Control. Release 1998; 51: 107–113.

J. Xiang, X. Fang, X. Li. Transbuccal delivery of 2V,3Vdideoxycytidine: in vitro permeation study and histological investigation. Int. J. Pharm 2002; 231 :57– 66

A.Ganem-Quintanar, Y.N. Kalia, F. Falson-Rieg, P. Buri. Mechanism of oral permeation enhancer. Int. J. Pharm 1997; 156: 127-142.

Y. Nakada, N. Awata, C. Nakamichi, I. Sugimoto. The effects of additives on the oral mucosal absorption of human calcitonin in rats. J. Pharmacobio-Dyn 1998; 11: 395-401.

C.K. Oh, W.A. Ritschel. Absorption characteristics of insulin through the buccal mucosa, Methods Find. Exp. Clin. Pharmacol 1990; 12: 275-279.

B.J. Aungst, N.J. Rogers. Comparison of the effects of various Transmucosal absorption promoters on buccal insulin delivery. Int. J. Pharm 1998; 53: 227-235

J.A. Hoogstraate, J.C. Verhoef, A. Pijpers, L.A.M.G. Van Leengoed, J.H.M. Verheiden, H.E. Junginger, H.E. BoddeÂ. In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs. Pharm. Res 1996; 13:1233-1237.

M. Ishida, Y. Machida, N. Nambu, T. Nagai. New mucosal dosage form of insulin. Chem. Pharm. Bull 1981; 29: 810-816.

M. Morishita, J.M. Barichello, K. Takayama, Y. Chiba, S. Tokiwa, T. Nagai. PluronicR F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin.Int. J. Pharm 2001; 212 : 289- 293.

K. Tsutsumi, Y. Obata, K. Takayama, T. Loftsson, T. Nagai. Effect of cod-liver oil extract on the buccal permeation of ergotamine tartrate. Drug Dev. Ind. Pharm 1998; 24:757- 762.

Y. Kurosaki, S. Hisaichi, T. Nakayama, T. Kimura. Enhancing effect of 1 dodecylaza cycloheptan-2-one (Azone) on the absorption of salicylic acid from keratinized oral mucosa and the duration of enhancement in vivo. Int. J. Pharm 1989; 51:47- 54.

Y. Kurosaki, S.I. Hisaichi, L.Z. Hong, T.Nakayama, T. Kimura. Enhanced permeability of keratinized oral-mucosa to salicylic acid with 1-dodecylazacycloheptan-2-one (Azone): in vitro studies in hamster cheek pouch. Int. J. Pharm 1989; 49: 47- 55.

J.A. Nicolazzo, B.L. Reed, B.C. Finnin. Modification of buccal drug delivery following pretreatment with skin penetration enhancers. J. Pharm. Sci 2004; 93:2054–2063.

A.N. Joseph, L.R. Barry, C.F. Barrie, Enhanced buccal mucosal retention and reduced buccal permeability of estradiol in the presence of padimate O and Azone®: a mech anistic study. J. Control. Release 2005; 94: 873–882.

J.A. Nicolazzo, B.L. Reed, B.C. Finnin. Enhancing the buccal mucosal uptake and retention of triamcinolone acetonide. J. Control. Release 2005; 105: 240–248.

B.J. Aungst, N.J. Rogers. Comparison of the effects of various Transmucosal absorption promoters on buccal insulin delivery. Int. J. Pharm 1989; 53: 227-235.

A. Steward, D.L. Bayley, C. Howes. The effect of enhancers on the buccal absorption of hybrid (BDBB) alpha-interferon. Int. J. Pharm 1994; 104: 145-149.

Hassan N, Ahad A, Ali M, Ali J. Chemical permeation enhancers for transbuccal drug delivery. Expert Opin Drug Deliv 2010; 7(1):97-112.

N.M. Howie, T.K. Trigkas, A.T. Cruchley, P.W. Wertz, C.A. Squier, D.M. Williams. Short-term exposure to alcohol increases the permeability of human oral mucosa. Oral Dis 2001; 7(6): 349–354.

M.J. Kremer, S. Senel, S.H. Kas, P.W. Wertz, A.A. Hincal, C.A. Squier. Oral mucosal drug delivery: chitosan as vehicle and permeabilizer. J. Dent. Res 1999; 77:718.

S. Senel, M.J. Kremer, S. Kas, P.W. Wertz, A.A. Hincal, C.A. Squier. Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials 2000; 21: 2067– 2071.

I.G. Needleman, F.C. Smales, G.P. Martin. An investigation of bioadhesion for periodontal and oral mucosal drug delivery. J. Clin. Periodontol 1997; 24: 394–400.

A. Portero, C. Remuna n-Lo pez, H.M. Nielsen. The potential of chitosan in enhancing peptide and protein absorption across the TR146 cell culture model—an in vitro model of the buccal epithelium. Pharm. Res 2002; 19:169– 174.

Palem CR, Kumar Battu S, Gannu R, Yamsani VV, Repka MA, Yamsani MR. Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: In vitro and ex vivo characterization. Pharm. Dev. Tech 2012; 17(3) 321-332.

Jacobsen J, Bjerregaard S, Pedersen M. Cyclodextrin inclusion complexes of anti mycotics intended to act in the oral cavity-drug supersaturation, toxicity on TR 146 cells and release from a delivery system. Eur. J. Pharm. Biopharm 1999; 48 (3):217-224.

N. Langoth, H. Kahlbacher, G. Schoffmann, I. Schmerold, M. Schuh, S. Franz, P.Kurka, A. Bernkop-Schnurch, Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system. Pharm. Res 2006; 23:573–579.

B.J. Aungst, N.J. Rogers. Dependence of absorption-promoting actions of laureth-9, salicylate, Na2EDTA, and aprotinin on rectal, nasal, and buccal insulin delivery. Pharm. Res 1988; 5: 305-308.

A.J. Hoogstraate, S. Senel, C. Cullander, J. Verhoef, H.E. Junginger, H.E. Bodde. Effects of bile salts on transport rates and routes of FITC-labelled compounds across porcine buccal epithelium in vivo. J. Control. Release 1996; 40: 211–221.

Nina Langoth, Andreas Bernkop-Schnürch, Peter Kurka. In Vitro Evaluation of Various Buccal Permeation Enhancing Systems for PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide). Pharmaceutical Research 2005; 22(12): 2045-2050.



How to Cite

DODLA, S., and S. VELMURUGAN. “BUCCAL PENETRATION ENHANCERS-AN OVERVIEW”. Asian Journal of Pharmaceutical and Clinical Research, vol. 6, no. 3, July 2013, pp. 39-47, https://innovareacademics.in/journals/index.php/ajpcr/article/view/176.