Drug Delivery from the Oral Cavity: A Focus on Mucoadhesive Buccal Drug Delivery Systems

Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. LAY ABSTRACT: Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.

[1]  H. Hägerström,et al.  Evaluation of mucoadhesion for two polyelectrolyte gels in simulated physiological conditions using a rheological method. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[2]  R. Khar,et al.  Measurement of bioadhesive strength of muco-adhesive buccal tablets: design of an in-vitro assembly , 1993 .

[3]  H. Yamano,et al.  Transport of D‐glucose across cultured stratified cell layer of human oral mucosal cells , 2002, The Journal of pharmacy and pharmacology.

[4]  Claus-Michael Lehr,et al.  An estimate of turnover time of intestinal mucus gel layer in the rat in situ loop , 1991 .

[5]  C. Lehr,et al.  Assessment of mucoadhesion by a resonant mirror biosensor. , 2006, International journal of pharmaceutics.

[6]  J. Remon,et al.  Direct compression properties of melt-extruded isomalt. , 2002, International journal of pharmaceutics.

[7]  Nikolaos A. Peppas,et al.  Pharmaceutical and Medical Aspects of Bioadhesive Systems for Drug Administration , 1988 .

[8]  D. Breimer,et al.  Improvement of drug absorption through enhancers , 1990, European Journal of Drug Metabolism and Pharmacokinetics.

[9]  H E Junginger,et al.  Developments in buccal drug delivery. , 1991, Critical reviews in therapeutic drug carrier systems.

[10]  J. Robinson,et al.  Bioadhesive-based dosage forms: the next generation. , 2000, Journal of pharmaceutical sciences.

[11]  J. Feijen,et al.  Interaction of cultured human endothelial cells with polymeric surfaces of different wettabilities. , 1985, Biomaterials.

[12]  H. M. Nielsen,et al.  TR146 cells grown on filters as a model of human buccal epithelium: IV. Permeability of water, mannitol, testosterone and beta-adrenoceptor antagonists. Comparison to human, monkey and porcine buccal mucosa. , 2000, International journal of pharmaceutics.

[13]  R. Gannu,et al.  Development of bioadhesive buccal tablets for felodipine and pioglitazone in combined dosage form: In vitro, ex vivo, and in vivo characterization , 2011, Drug delivery.

[14]  Majella E Lane,et al.  Skin penetration enhancers. , 2013, International journal of pharmaceutics.

[15]  Y. Chien,et al.  Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced transmucosal permeation. , 1996, Pharmaceutical development and technology (Print).

[16]  Xiaoling Li,et al.  Advances in buccal drug delivery. , 2005, Critical reviews in therapeutic drug carrier systems.

[17]  J. Cassidy,et al.  Buccal and colonic absorption of CGS 16617, a novel ACE inhibitor , 1992 .

[18]  B. Jayakar,et al.  In vivo bioavailability studies of sumatriptan succinate buccal tablets , 2011, DARU.

[19]  T. Nagai,et al.  In vitro and in vivo nasal mucoadhesion of some water-soluble polymers , 1996 .

[20]  A. Domb,et al.  Efficacy of a Mucoadhesive Patch Compared with an Oral Solution for Treatment of Aphthous Stomatitis , 2008, Drugs in R&D.

[21]  Véronique Préat,et al.  Skin electroporation for transdermal and topical delivery. , 2004, Advanced drug delivery reviews.

[22]  D. Breimer,et al.  Pharmacokinetics of Rectal Drug Administration, Part I , 1991, Clinical pharmacokinetics.

[23]  Aarti Naik,et al.  Iontophoretic drug delivery. , 2004, Advanced drug delivery reviews.

[24]  B. Aungst,et al.  Development and in vivo evaluation of buccal tablets prepared using danazol-sulfobutylether 7 beta-cyclodextrin (SBE 7) complexes. , 2002, Journal of pharmaceutical sciences.

[25]  J D Smart,et al.  An investigation of mucus/polymer rheological synergism using synthesised and characterised poly(acrylic acid)s. , 2001, International journal of pharmaceutics.

[26]  S. Mortazavi,et al.  An investigation into the role of water movement and mucus gel dehydration in mucoadhesion , 1993 .

[27]  Kinam Park A new approach to study mucoadhesion: colloidal gold staining , 1989 .

[28]  A. Bandyopadhyay,et al.  Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[29]  H. Boddé,et al.  Diffusion rates and transport pathways of FITC-labelled model compounds through buccal epithelium , 1994 .

[30]  L. Nielsen,et al.  Bioadhesive drug delivery systems: I. Characterisation of mucoadhesive properties of systems based on glyceryl mono-oleate and glyceryl monolinoleate , 1998 .

[31]  Y. Kalia,et al.  Factors and strategies for improving buccal absorption of peptides. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[32]  N. Nafee,et al.  Mucoadhesive Delivery Systems. I. Evaluation of Mucoadhesive Polymers for Buccal Tablet Formulation , 2004, Drug development and industrial pharmacy.

[33]  C. Lehr,et al.  Lectin-mediated drug delivery: the second generation of bioadhesives. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[34]  G. Fetih,et al.  Transbuccal permeation, anti-inflammatory activity and clinical efficacy of piroxicam formulated in different gels. , 2004, International journal of pharmaceutics.

[35]  Nili Grossman,et al.  Bubble growth within the skin by rectified diffusion might play a significant role in sonophoresis. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[36]  M. Bruschi,et al.  Oral Bioadhesive Drug Delivery Systems , 2005, Drug development and industrial pharmacy.

[37]  M. Rathbone,et al.  The oral cavity as a site for systemic drug delivery , 1994 .

[38]  R. E. King Oral Solid Dosage Forms , 2022 .

[39]  Nikolaos A. Peppas,et al.  Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues , 1985 .

[40]  Qiang Zhang,et al.  Phospholipid deformable vesicles for buccal delivery of insulin. , 2002, Chemical & pharmaceutical bulletin.

[41]  C. Squier,et al.  The permeability of skin and oral mucosa to water and horseradish peroxidase as related to the thickness of the permeability barrier. , 1985, The Journal of investigative dermatology.

[42]  R. Kinget,et al.  Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives. , 2005, Advanced drug delivery reviews.

[43]  R. Khanna,et al.  Mucoadhesive Buccal Drug Delivery : A Potential Alternative To Conventional Therapy , 1998 .

[44]  J. Robinson,et al.  Transport of Thyrotropin Releasing Hormone in Rabbit Buccal Mucosa in Vitro , 1992, Pharmaceutical Research.

[45]  J. Robinson,et al.  Drug delivery via the mucous membranes of the oral cavity. , 1992, Journal of pharmaceutical sciences.

[46]  H. Merkle,et al.  Evaluation of laminated muco-adhesive patches for buccal drug delivery , 1989 .

[47]  Y. Machida,et al.  Biodegradation and distribution of water-soluble chitosan in mice. , 1999, Biomaterials.

[48]  J. Robinson,et al.  Preliminary studies of oral mucosal delivery of peptide drugs , 1987 .

[49]  J. Gallo,et al.  A Simple Rheological Method for the in Vitro Assessment of Mucin-Polymer Bioadhesive Bond Strength , 1990, Pharmaceutical Research.

[50]  Beckett Ah,et al.  Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. , 1967 .

[51]  P Chinna Reddy,et al.  A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods , 2011, Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences.

[52]  Y. Huang,et al.  Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[53]  S. H. Leung,et al.  Binding of acrylic polymers to mucin/epithelial surfaces: structure-property relationships. , 1988, Critical reviews in therapeutic drug carrier systems.

[54]  M. Jug,et al.  Influence of hydroxypropyl-beta-cyclodextrin complexation on piroxicam release from buccoadhesive tablets. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[55]  R. Khar,et al.  Development And Evaluation Of Mucoadhesive films of Miconazole Nitrate , 2000 .

[56]  J. Robinson,et al.  Enzyme characterization studies on the rate-limiting barrier in rabbit buccal mucosa , 1992 .

[57]  E. Triggs,et al.  Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. , 1967, The Journal of pharmacy and pharmacology.

[58]  J. Nicolazzo,et al.  Buccal penetration enhancers--how do they really work? , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[59]  D. J. White,et al.  On the wettability of soft tissues in the human oral cavity. , 2004, Archives of oral biology.

[60]  David S. Jones,et al.  Mucoadhesive polymeric platforms for controlled drug delivery. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[61]  S. A. Nirmal,et al.  Polymers for Mucoadhesive Drug Delivery System: A Current Status , 2008 .

[62]  P. van der Bijl,et al.  Comparative permeability of various chemical markers through human vaginal and buccal mucosa as well as porcine buccal and mouth floor mucosa. , 2004, Archives of oral biology.

[63]  N. Nafee,et al.  Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. , 2003, Acta pharmaceutica.

[64]  P. Madan,et al.  Evaluation of polyoxyethylene homopolymers for buccal bioadhesive drug delivery device formulations , 1999, AAPS PharmSci.

[65]  D. Magermans Biomechanical analysis of shoulder arthroplasty , 2004 .

[66]  G. Campisi,et al.  Current status in buccal drug delivery , 2008 .

[67]  V. Lenaerts,et al.  Bioadhesive Drug Delivery Systems , 1989 .

[68]  P. McCarron,et al.  Potential of photodynamic therapy in treatment of fungal infections of the mouth. Design and characterisation of a mucoadhesive patch containing toluidine blue O. , 2007, Journal of photochemistry and photobiology. B, Biology.

[69]  M. Marsh,et al.  Binding and entry of animal viruses , 1989, Advanced Drug Delivery Reviews.

[70]  O. Güven,et al.  Design and evaluation of sustained-release and buccal adhesive propranolol hydrochloride tablets , 1996 .

[71]  B. Hirst,et al.  Lectin-mediated mucosal delivery of drugs and microparticles. , 2000, Advanced drug delivery reviews.

[72]  Dimitra Dodou,et al.  Mucoadhesives in the gastrointestinal tract: revisiting the literature for novel applications. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[73]  Y. Rao,et al.  In vitro and in vivo adhesion testing of mucoadhesive drug delivery systems. , 1999, Drug development and industrial pharmacy.

[74]  Kinam Park,et al.  Bioadhesive polymers as platforms for oral-controlled drug delivery: method to study bioadhesion , 1984 .

[75]  J. Irache,et al.  Bioadhesive Properties of Gantrez Nanoparticles , 2005, Molecules.

[76]  Charles E. Martin,et al.  Single-Screw Extrusion and Screw Design , 2003 .

[77]  H E Junginger,et al.  Recent advances in buccal drug delivery and absorption--in vitro and in vivo studies. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[78]  J. Robinson,et al.  BIOADHESIVE POLYMERS AS PLATFORM FOR ORAL CONTROLLED DRUG DELIVERY , 1985 .

[79]  J. Robinson,et al.  Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers. , 1985, Journal of pharmaceutical sciences.

[80]  C. Squier,et al.  The Structure and Function of Oral Mucosa , 1984 .

[81]  B Claustrat,et al.  Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin. , 1997, Journal of pharmaceutical sciences.

[82]  E. Mathiowitz,et al.  NOVEL MAGNETIC TECHNIQUE TO MEASURE BIOADHESION , 1999 .

[83]  Donald L. Wise,et al.  Handbook of Pharmaceutical Controlled Release Technology , 2000 .

[84]  M D Donovan,et al.  Drug transfer through mucus. , 2001, Advanced drug delivery reviews.

[85]  S. C. Ullyot Paediatric premedication , 1992, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[86]  Montakarn Chittchang,et al.  The use of mucoadhesive polymers in buccal drug delivery. , 2005, Advanced drug delivery reviews.

[87]  Javed Ali,et al.  Mucoadhesive Drug Delivery Systems , 1997 .

[88]  H. Noteborn,et al.  Drug delivery systems. , 1989, Current opinion in oncology.

[89]  M. Roberts,et al.  Transdermal delivery of drugs by iontophoresis: a review. , 1989, Drug design and delivery.

[90]  B. Kemppainen,et al.  In vitro penetration of tritium-labelled water (THO) and [3H]PbTx-3 (a red tide toxin) through monkey buccal mucosa and skin. , 1991, Toxicology letters.

[91]  J. Robinson,et al.  Alternative Approaches to Oral Controlled Drug Delivery: Bioadhesives and In-Situ Systems , 1984 .

[92]  A. Shojaei Buccal mucosa as a route for systemic drug delivery: a review. , 1998, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[93]  I. Kellaway,et al.  Buccal permeation of [D-Ala(2), D-Leu(5)]enkephalin from liquid crystalline phases of glyceryl monooleate. , 2000, International journal of pharmaceutics.

[94]  B. Lipworth,et al.  Clinical Pharmacokinetics of Drugs Administered Buccally and Sublingually , 1991, Clinical pharmacokinetics.

[95]  R. Gannu,et al.  Development of bilayered mucoadhesive patches for buccal delivery of felodipine: in vitro and ex vivo characterization , 2010 .

[96]  M. Mihic,et al.  The evolving role of oral insulin in the treatment of diabetes using a novel RapidMist™ System , 2002, Diabetes/metabolism research and reviews.

[97]  V. Karde,et al.  MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM: A REVIEW , 2013 .

[98]  S. Mitragotri,et al.  Low-frequency sonophoresis: a review. , 2004, Advanced drug delivery reviews.

[99]  R. Mcquinn,et al.  Sustained oral mucosal delivery in human volunteers of buprenorphine from a thin non-eroding mucoadhesive polymeric disk , 1995 .

[100]  Joseph R. Robinson,et al.  Mechanisms of Mucoadhesion of Poly(acrylic Acid) Hydrogels , 1987, Pharmaceutical Research.

[101]  D. Coomans,et al.  Development and Testing of Bioadhesive, Fluoride‐containing Slow‐release Tablets for Oral Use , 1991, The Journal of pharmacy and pharmacology.

[102]  B. Derjaguin,et al.  Electronic Theory of Adhesion , 1967 .

[103]  J. Robinson,et al.  Oral cavity as a site for bioadhesive drug delivery , 1994 .

[104]  J. Robinson,et al.  Physico-chemical properties of water insoluble polymers important to mucin/epithelial adhesion☆ , 1985 .

[105]  J. Swarbrick,et al.  Encyclopedia of Pharmaceutical Technology , 2006 .

[106]  D. Williams,et al.  The Permeability of Human Oral Mucosa and Skin to Water , 1989, Journal of dental research.

[107]  A. Mikos,et al.  Bioadhesive analysis of controlled-release systems. IV. An experimental method for testing the adhesion of microparticles with mucus , 1990 .

[108]  K. Foley,et al.  Sublingual absorption of selected opioid analgesics , 1988, Clinical pharmacology and therapeutics.

[109]  Rahamatullah Shaikh,et al.  Mucoadhesive drug delivery systems , 2011, Journal of pharmacy & bioallied sciences.

[110]  K. Erdmann,et al.  [The effect of rectal pH values on the absorption of methohexital]. , 1986, Der Anaesthesist.

[111]  S. Sreenivas,et al.  Design and evaluation of gastroretentive mucoadhesive cephalexin tablets. , 2009, Pharmaceutical development and technology (Print).