U.S. flag

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

  • Publications
  • Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

  • Advanced Search
  • Journal List
  • J Adv Pharm Technol Res
  • v.1(4); Oct-Dec 2010

Mucoadhesive drug delivery system: An overview

Bindu m. boddupalli.

Department of Pharmaceutics, Nalanda College of Pharmacy, Nalgonda, Andhra Pradesh - 508 001, India

Zulkar N. K. Mohammed

Ravinder a. nath.

1 Faculty of Technology, Osmania University, Hyderabad, Andhra Pradesh – 500 013, India

David Banji

Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms.

INTRODUCTION

Since the early 1980s, the concept of mucoadhesion has gained considerable interest in pharmaceutical technology.[ 1 ] Adhesion can be defined as the bond produced by contact between a pressure sensitive adhesive and a surface. The American Society of Testing and Materials has defined it as the state in which two surfaces are held together by interfacial forces, which may consist of valence forces, interlocking action or both. Mucoadhesive drug delivery systems prolong the residence time of the dosage form at the site of application or absorption. They facilitate an intimate contact of the dosage form with the underlying absorption surface and thus improve the therapeutic performance of the drug. In recent years, many such mucoadhesive drug delivery systems have been developed for oral, buccal, nasal, rectal and vaginal routes for both systemic and local effects.[ 2 ]

Dosage forms designed for mucoadhesive drug delivery should be small and flexible enough to be acceptable for patients and should not cause irritation. Other desired characteristics of a mucoadhesive dosage form include high drug loading capacity, controlled drug release (preferably unidirectional release), good mucoadhesive properties, smooth surface, tastelessness, and convenient application. Erodible formulations can be beneficial because they do not require system retrieval at the end of desired dosing interval. A number of relevant mucoadhesive dosage forms have been developed for a variety of drugs. Several peptides, including thyrotropin-releasing hormone (TRH), insulin, octreotide, leuprolide, and oxytocin, have been delivered via the mucosal route, albeit with relatively low bioavailability (0.1–5%),[ 3 ] owing to their hydrophilicity and large molecular weight, as well as the inherent permeation and enzymatic barriers of the mucosa.

The development of sustain release dosage form can achieve the aim of releasing the drug slowly for a long period but this is not sufficient to get sustained therapeutic effect. They may be cleared from the site of absorption before emptying the drug content. Instead, the mucoadhesive dosage form will serve both the purposes of sustain release and presence of dosage form at the site of absorption. In this regard, our review is high lighting few aspects of mucoadhesive drug delivery systems.

ADVANTAGES OF MUCOADHESIVE DRUG DELIVERY SYSTEM

Mucoadhesive delivery systems offer several advantages over other oral controlled release systems by virtue of prolongation of residence time of drug in gastrointestinal tract (GIT).

  • Targeting and localization of the dosage form at a specific site.
  • Also, the mucoadhesive systems are known to provide intimate contact between dosage form and the absorptive mucosa, resulting in high drug flux at the absorbing tissue.[ 4 ]

Mucus Membranes

Mucus membranes (mucosae) [ Figure 1 ] are the moist surfaces lining the walls of various body cavities such as the gastrointestinal and respiratory tracts. They consist of a connective tissue layer (the lamina propria) above which is an epithelial layer, the surface of which is made moist usually by the presence of a mucus layer. The epithelia may be either single layered (e.g. the stomach, small and large intestines and bronchi) or multilayered/stratified (e.g. in the esophagus, vagina and cornea). The former contain goblet cells which secrete mucus directly onto the epithelial surfaces; the latter contain, or are adjacent to tissues containing, specialized glands such as salivary glands that secrete mucus onto the epithelial surface. Mucus is present either as a gel layer adherent to the mucosal surface or as a luminal soluble or suspended form. The major components of all mucus gels are mucin glycoproteins, lipids, inorganic salts and water, the latter accounting for more than 95% of their weight, making them a highly hydrated system.[ 5 ] The major functions of mucus are that of protection and lubrication.

An external file that holds a picture, illustration, etc.
Object name is JAPTR-1-381-g001.jpg

Mucus membrane structure

Mechanisms of Mucoadhesion

The mechanism of mucoadhesion is generally divided into two steps: the contact stage and the consolidation stage [ Figure 2 ]. The first stage is characterized by the contact between the mucoadhesive and the mucus membrane, with spreading and swelling of the formulation, initiating its deep contact with the mucus layer.[ 6 ]

An external file that holds a picture, illustration, etc.
Object name is JAPTR-1-381-g002.jpg

The process of contact and consolidation

In the consolidation step [ Figure 2 ], the mucoadhesive materials are activated by the presence of moisture. Moisture plasticizes the system, allowing the mucoadhesive molecules to break free and to link up by weak van der Waals and hydrogen bonds. Essentially, there are two theories explaining the consolidation step: the diffusion theory and the dehydration theory. According to the diffusion theory, the mucoadhesive molecules and the glycoproteins of the mucus mutually interact by means of interpenetration of their chains and the building of secondary bonds. For this to take place, the mucoadhesive device has features favoring both chemical and mechanical interactions. For example, molecules with hydrogen bond building groups (–OH, –COOH), an anionic surface charge, high molecular weight, flexible chains and surface-active properties, which help in spreading throughout the mucus layer, can present mucoadhesive properties.[ 6 ]

Mucoadhesion Theories

Mucoadhesion is a complex process and numerous theories have been proposed to explain the mechanisms involved. These theories include mechanical interlocking, electrostatic, diffusion interpenetration, adsorption and fracture processes.

Wetting theory

The wetting theory applies to liquid systems which present affinity to the surface in order to spread over it. This affinity can be found by using measuring techniques such as the contact angle. The general rule states that the lower the contact angle, the greater is the affinity [ Figure 3 ]. The contact angle should be equal or close to zero to provide adequate spreadability. The spreadability coefficient, S AB , can be calculated from the difference between the surface energies γ B and γ A and the interfacial energy γ AB , as indicated in the equation given below.[ 5 ] This theory explains the importance of contact angle and reduction of surface and interfacial energies to achieve good amount of mucoadhesion.

An external file that holds a picture, illustration, etc.
Object name is JAPTR-1-381-g003.jpg

Influence of contact angle on mucoadhesion

S AB = γ B – γ A – γ AB

Diffusion theory

Diffusion theory describes the interpenetration of both polymer and mucin chains to a sufficient depth to create a semi-permanent adhesive bond [ Figure 4 ]. It is believed that the adhesion force increases with the degree of penetration of the polymer chains. This penetration rate depends on the diffusion coefficient, flexibility and nature of the mucoadhesive chains, mobility and contact time. According to the literature, the depth of interpenetration required to produce an efficient bioadhesive bond lies in the range 0.2–0.5 μm. This interpenetration depth of polymer and mucin chains can be estimated by the following equation:[ 5 ]

An external file that holds a picture, illustration, etc.
Object name is JAPTR-1-381-g004.jpg

Secondary interaction between mucoadhesive device and of mucus

l = ( tD b )½

where t is the contact time and D b is the diffusion coefficient of the mucoadhesive material in the mucus. The adhesion strength for a polymer is reached when the depth of penetration is approximately equivalent to the polymer chain size. In order for diffusion to occur, it is important that the components involved have good mutual solubility, that is, both the bioadhesive and the mucus have similar chemical structures. The greater the structural similarity, the better is the mucoadhesive bond.[ 5 ]

Fracture theory

This is perhaps the most used theory in studies on the mechanical measurement of mucoadhesion. It analyzes the force required to separate two surfaces after adhesion is established. This force, s m , is frequently calculated in tests of resistance to rupture by the ratio of the maximal detachment force, F m , and the total surface area, A 0 , involved in the adhesive interaction

An external file that holds a picture, illustration, etc.
Object name is JAPTR-1-381-g005.jpg

Since the fracture theory [ Figure 5 ] is concerned only with the force required to separate the parts, it does not take into account the interpenetration or diffusion of polymer chains. Consequently, it is appropriate for use in the calculations for rigid or semi-rigid bioadhesive materials, in which the polymer chains do not penetrate into the mucus layer.[ 5 , 6 ]

An external file that holds a picture, illustration, etc.
Object name is JAPTR-1-381-g006.jpg

Fractures occurring for mucoadhesion

The electronic theory

This theory describes adhesion occurring by means of electron transfer between the mucus and the mucoadhesive system, arising through differences in their electronic structures. The electron transfer between the mucus and the mucoadhesive results in the formation of double layer of electrical charges at the mucus and mucoadhesive interface. The net result of such a process is the formation of attractive forces within this double layer.[ 7 ]

The adsorption theory

In this instance, adhesion is the result of various surface interactions (primary and secondary bonding) between the adhesive polymer and mucus substrate. Primary bonds due to chemisorptions result in adhesion due to ionic, covalent and metallic bonding, which is generally undesirable due to their permanency.[ 8 ] Secondary bonds arise mainly due to van der Waals forces, hydrophobic interactions and hydrogen bonding. Whilst these interactions require less energy to “break”, they are the most prominent form of surface interaction in mucoadhesion processes as they have the advantage of being semi-permanent bonds.[ 9 ]

All these numerous theories should be considered as supplementary processes involved in the different stages of the mucus/substrate interaction, rather than individual and alternative theories. Each and every theory is equally important to describe the mucoadhesion process. There is a possibility that there will be initial wetting of the mucin, and then diffusion of the polymer into mucin layer, thus causing the fracture in the layers to effect the adhesion or electronic transfer or simple adsorption phenomenon that finally leads to the perfect mucoadhesion. The mechanism by which a mucoadhesive bond is formed will depend on the nature of the mucus membrane and mucoadhesive material, the type of formulation, the attachment process and the subsequent environment of the bond. It is apparent that a single mechanism for mucoadhesion proposed in many texts is unlikely for all the different occasions when adhesion occurs.

Factors Affecting Mucoadhesion

Molecular weight.

The mucoadhesive strength of a polymer increases with molecular weights above 100,000. Direct correlation between the mucoadhesive strength of polyoxyethylene polymers and their molecular weights lies in the range of 200,000–7,000,000.[ 10 ]

Flexibility

Mucoadhesion starts with the diffusion of the polymer chains in the interfacial region. Therefore, it is important that the polymer chains contain a substantial degree of flexibility in order to achieve the desired entanglement with the mucus.[ 11 ] The increased chain interpenetration was attributed to the increased structural flexibility of the polymer upon incorporation of polyethylene glycol. In general, mobility and flexibility of polymers can be related to their viscosities and diffusion coefficients, as higher flexibility of a polymer causes greater diffusion into the mucus network.[ 12 ]

Cross-linking density

The average pore size, the number and average molecular weight of the cross-linked polymers, and the density of cross-linking are three important and inter-related structural parameters of a polymer network. Therefore, it seems reasonable that with increasing density of cross-linking, diffusion of water into the polymer network occurs at a lower rate which, in turn, causes an insufficient swelling of the polymer and a decreased rate of interpenetration between polymer and mucin.[ 12 ]

Hydrogen bonding capacity

Hydrogen bonding is another important factor in mucoadhesion of a polymer. Desired polymers must have functional groups that are able to form hydrogen bonds, and flexibility of the polymer is important to improve this hydrogen bonding potential.[ 12 ] Polymers such as poly(vinyl alcohol), hydroxylated methacrylate, and poly(methacrylic acid), as well as all their copolymers, have good hydrogen bonding capacity.[ 13 ]

Hydration is required for a mucoadhesive polymer to expand and create a proper macromolecular mes of sufficient size, and also to induce mobility in the polymer chains in order to enhance the interpenetration process between polymer and mucin. Polymer swelling permits a mechanical entanglement by exposing the bioadhesive sites for hydrogen bonding and/or electrostatic interaction between the polymer and the mucus network.[ 12 ] However, a critical degree of hydration of the mucoadhesive polymer exists where optimum swelling and mucoadhesion occurs.[ 13 ]

Some generalizations about the charge of bioadhesive polymers have been made previously, where nonionic polymers appear to undergo a smaller degree of adhesion compared to anionic polymers. Strong anionic charge on the polymer is one of the required characteristics for mucoadhesion.[ 13 ] Some cationic polymers are likely to demonstrate superior mucoadhesive properties, especially in a neutral or slightly alkaline medium.[ 14 ] Additionally, some cationic high–molecular-weight polymers, such as chitosan, have shown to possess good adhesive properties.[ 15 ] There is no significant literature about the influence of the charge of the membrane on the mucoadhesion but the pH of the membrane affects the mucoadhesion as it can influence the ionized or un-ionized forms of the polymers.[ 16 ]

Concentration

The importance of this factor lies in the development of a strong adhesive bond with the mucus, and can be explained by the polymer chain length available for penetration into the mucus layer. When the concentration of the polymer is too low, the number of penetrating polymer chains per unit volume of the mucus is small and the interaction between polymer and mucus is unstable. In general, the more concentrated polymer would result in a longer penetrating chain length and better adhesion. However, for each polymer, there is a critical concentration, above which the polymer produces an “unperturbed” state due to a significantly coiled structure. As a result, the accessibility of the solvent to the polymer decreases, and chain penetration of the polymer is drastically reduced. Therefore, higher concentrations of polymers do not necessarily improve and, in some cases, actually diminish mucoadhesive properties. One of the studies addressing this factor demonstrated that high concentrations of flexible polymeric films based on polyvinylpyrrolidone or poly(vinyl alcohol) as film-forming polymers did not further enhance the mucoadhesive properties of the polymer.[ 17 ]

Sites for Mucoadhesive Drug Delivery Systems

The common sites of application where mucoadhesive polymers have the ability to deliver pharmacologically active agents include oral cavity, eye conjunctiva, vagina, nasal cavity and GIT.

The buccal cavity has a very limited surface area of around 50 cm 2 but the easy access to the site makes it a preferred location for delivering active agents. The site provides an opportunity to deliver pharmacologically active agents systemically by avoiding hepatic first-pass metabolism in addition to the local treatment of the oral lesions.

The sublingual mucosa is relatively more permeable than the buccal mucosa due to the presence of large number of smooth muscle and immobile mucosa. Hence, formulations for sublingual delivery are designed to release the active agent quickly while mucoadhesive formulation is of importance for the delivery of active agents to the buccal mucosa, where the active agent has to be released in a controlled manner. This makes the buccal cavity more suitable for mucoadhesive drug delivery.[ 18 ] The various mucoadhesive polymers used for the development of buccal delivery systems include cyanoacrylates, polyacrylic acid, sodium carboxymethylcellulose, hyaluronic acid, hydroxypropylcellulose, polycarbophil, chitosan and gellan. The delivery systems are generally coated with a drug and water impermeable film so as to prevent the washing of the active agent by the saliva.[ 19 ]

Like buccal cavity, nasal cavity also provides a potential site for the development of formulations where mucoadhesive polymers can play an important role. The nasal mucosal layer has a surface area of around 150–200 cm 2 . The residence time of a particulate matter in the nasal mucosa varies between 15 and 30 min, which has been attributed to the increased activity of the mucociliary layer in the presence of foreign particulate matter. The polymers used in the development of formulations for the development of nasal delivery system include copolymer of methyl vinyl ether, hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose, carbopol-934P and Eudragit RL-100.[ 20 , 21 ]

Due to the continuous formation of tears and blinking of eye lids, there is a rapid removal of the active medicament from the ocular cavity, which results in the poor bioavailability of the active agents. This can be minimized by delivering the drugs using ocular insert or patches. The mucoadhesive polymers used for the ocular delivery include thiolated poly(acrylic acid), poloxamer, celluloseacetophthalate, methyl cellulose, hydroxy ethyl cellulose, poly(amidoamine) dendrimers, poly(dimethyl siloxane) and poly(vinyl pyrrolidone).[ 22 , 23 ]

The vaginal and the rectal lumen have also been explored for the delivery of the active agents both systemically and locally. The active agents meant for the systemic delivery by this route of administration bypass the hepatic first-pass metabolism. Quite often, the delivery systems suffer from migration within the vaginal/rectal lumen, which might affect the delivery of the active agent to the specific location. The use of mucoadhesive polymers for the development of delivery system helps in reducing the migration of the same, thereby promoting better therapeutic efficacy. The polymers used in the development of vaginal and rectal delivery systems include mucin, gelatin, polycarbophil and poloxamer.[ 24 – 26 ]

GIT is also a potential site which has been explored for a long time for the development of mucoadhesive based formulations. The modulation of the transit time of the delivery systems in a particular location of the gastrointestinal system by using mucoadhesive polymers has generated much interest among researchers around the world. The various mucoadhesive polymers which have been used for the development of oral delivery systems include chitosan, poly(acrylic acid), alginate, poly(methacrylic acid) and sodium carboxymethyl cellulose.[ 27 ]

Each site of mucoadhesion has its own advantages and disadvantages along with the basic property of prolonged residence of dosage form at that particular site. In buccal and sublingual sites, there is an advantage of fast onset along with bypassing the first-pass metabolism, but these sites suffer from inconvenience because of taste and intake of food. In GIT, there is a chance for improved amount of absorption because of microvilli, but it has a drawback of acid instability and first-pass effects. Rectal and vaginal sites are the best ones for the local action of the drug but they suffer from inconvenience of administration. Nasal and ophthalmic routes have another drawback of mucociliary drainage that would clear the dosage form from the site.

Mucoadhesive Dosage Forms

Tablets are small, flat, and oval, with a diameter of approximately 5–8 mm.[ 28 ] Unlike the conventional tablets, mucoadhesive tablets allow for drinking and speaking without major discomfort. They soften, adhere to the mucosa, and are retained in position until dissolution and/or release is complete. Mucoadhesive tablets, in general, have the potential to be used for controlled release drug delivery, but coupling of mucoadhesive properties to tablet has additional advantages, for example, it offers efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio and facilitates a much more intimate contact with the mucus layer. Mucoadhesive tablets can be tailored to adhere to any mucosal tissue including those found in stomach, thus offering the possibilities of localized as well as systemic controlled release of drugs. The application of mucoadhesive tablets to the mucosal tissues of gastric epithelium is used for administration of drugs for localized action. Mucoadhesive tablets are widely used because they release the drug for a prolonged period, reduce frequency of drug administration and improve the patient compliance. The major drawback of mucoadhesive tablets is their lack of physical flexibility, leading to poor patient compliance for long-term and repeated use.[ 29 – 31 ]

Mucoadhesive films may be preferred over adhesive tablets in terms of flexibility and comfort. In addition, they can circumvent the relatively short residence time of oral gels on the mucosa, which are easily washed away and removed by saliva. Moreover, in the case of local delivery for oral diseases, the films also help protect the wound surface, thus helping to reduce pain, and treat the disease more effectively. An ideal film should be flexible, elastic, and soft, yet adequately strong to withstand breakage due to stress from mouth movements. It must also possess good mucoadhesive strength in order to be retained in the mouth for the desired duration of action. Swelling of film, if it occurs, should not be too extensive in order to prevent discomfort.[ 32 ]

Patches are laminates consisting of an impermeable backing layer, a drug-containing reservoir layer from which the drug is released in a controlled manner, and a mucoadhesive surface for mucosal attachment. Patch systems are similar to those used in transdermal drug delivery. Two methods used to prepare adhesive patches include solvent casting and direct milling. In the solvent casting method, the intermediate sheet from which patches are punched is prepared by casting the solution of the drug and polymer(s) onto a backing layer sheet, and subsequently allowing the solvent(s) to evaporate. In the direct milling method, formulation constituents are homogeneously mixed and compressed to the desired thickness, and patches of predetermined size and shape are then cut or punched out. An impermeable backing layer may also be applied to control the direction of drug release, prevent drug loss, and minimize deformation and disintegration of the device during the application period.[ 33 , 34 ]

Gels and ointments

Semisolid dosage forms, such as gels and ointments, have the advantage of easy dispersion throughout the oral mucosa. However, drug dosing from semisolid dosage forms may not be as accurate as from tablets, patches, or films. Poor retention of the gels at the site of application has been overcome by using mucoadhesive formulations. Certain mucoadhesive polymers, for example, sodium carboxymethylcellulose,[ 35 ] carbopol,[ 36 ] hyaluronic acid,[ 37 ] and xanthan gum,[ 38 ] undergo a phase change from liquid to semisolid. This change enhances the viscosity, which results in sustained and controlled release of drugs. Hydrogels are also a promising dosage form for buccal drug delivery. They are formed from polymers that are hydrated in an aqueous environment and physically entrap drug molecules for subsequent slow release by diffusion or erosion.[ 39 ] The application of mucoadhesive gels provides an extended retention time in the oral cavity, adequate drug penetration, as well as high efficacy and patient acceptability. A major application of adhesive gels is the local delivery of medicinal agents for the treatment of periodontitis, which is an inflammatory and infectious disease that causes formation of pockets between the gum and the tooth, and can eventually cause loss of teeth. It has been suggested that mucoadhesive polymers might be useful for periodontitis therapy when incorporated in antimicrobial-containing formulations that are easily introduced into the periodontal pocket with a syringe.[ 40 – 42 ] HPMC has been used as an adhesive ointment ingredient. Additionally, a highly viscous gel was developed from carbopal and hydroxypropylcellulose for ointment dosage forms that could be maintained on the tissue for up to 8 hours.[ 2 ]

This overview about the mucoadhesive dosage forms might be a useful tool for the efficient design of novel mucoadhesive drug delivery systems. Mucoadhesive drug delivery systems have applications from different angles, including development of novel mucoadhesives, design of the device, mechanisms of mucoadhesion and permeation enhancement. With the influx of a large number of new drug molecules due to drug discovery, mucoadhesive drug delivery will play an even more important role in delivering these molecules.

ACKNOWLEDGMENTS

The authors wish to thank the Management and HOD, Department of Pharmaceutics, Nalanda College of Pharmacy, Nalgonda, AP, India, and also Faculty of Pharmacy, Osmania University, for providing facilities to carry out this review work.

Source of Support: Nil

Conflict of Interest: Nil.

Recent Advancements and Patents on Buccal Drug Delivery Systems: A Comprehensive Review

Affiliation.

  • 1 Department of Pharmaceutics, Faculty of Pharmacy, Amity University Uttar Pradesh, Lucknow, India.
  • PMID: 34126916
  • DOI: 10.2174/1872210515666210609145144

The major requirement for a dosage form to be successful is its ability to penetrate the site of application and the bioavailability of the drug released from the dosage form. The buccal drug delivery is an influential route to deliver the drug into the body. Here, in this context, various novel approaches that include lipoidal carriers like ethosomes, transferosomes, niosomes etc. and electrospun nanofibers are discussed, with respect to buccal drug delivery. These carriers can be easily incorporated into buccal dosage forms like patches and gels that are responsible for increased permeation across the buccal epithelium. The in vivo methods of evaluation on animal models are conscribed here. The novel biocarriers of lipoidal and non-lipoidal nature can be utilized by loading the drug into them, which are helpful in preventing drug degradation and other drawbacks as compared to conventional formulations. The globally patented buccal formulations give us a wide context in literature about the patents filed and granted in the recent years. When it comes to patient compliance, age is an issue, which is also solved by the buccal route. The pediatric buccal formulations are researched for the customization to be delivered to children. Diseases like mouth ulcers, oral cancer, Parkinson's disease, aphthous stomatitis etc. have been successfully treated through the buccal route, which infers that the buccal drug delivery system is an effective and emerging area for formulation and development in the field of pharmaceutics.

Keywords: Buccal; animal models; buccal mucosa; diseases; lipid carriers; patents; penetration.

Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Publication types

  • Administration, Buccal
  • Drug Delivery Systems
  • Mouth Mucosa* / metabolism
  • Patents as Topic*
  • Pharmaceutical Preparations / metabolism
  • Pharmaceutical Preparations

Advertisement

Advertisement

Drug delivery techniques for buccal route: formulation strategies and recent advances in dosage form design

  • Published: 15 October 2016
  • Volume 46 , pages 593–613, ( 2016 )

Cite this article

research articles on buccal drug delivery system

  • Sonia Barua 1 ,
  • Hyeongmin Kim 1 ,
  • Kanghee Jo 1 ,
  • Chang Won Seo 1 ,
  • Tae Jun Park 1 ,
  • Kyung Bin Lee 1 ,
  • Gyiae Yun 2 ,
  • Kyungsoo Oh 1 &
  • Jaehwi Lee 1  

1796 Accesses

22 Citations

Explore all metrics

The buccal mucosa has been investigated for the local drug therapy and the systemic delivery of potent peptides, proteins, and other small drug molecules that are subjected to hepatic metabolism and enzymatic degradation in the gastrointestinal tract. Being non-invasive, this route is more feasible for the delivery of therapeutic entities than that of invasive or parenteral drug administration. However, the mucosa of oral cavity represents a major barrier to drug penetration. In addition, the presence of several enzymes in saliva, salivary flow, discomfort feelings after administration of dosage forms, and bitter taste of the drugs have limited the drug delivery via the buccal cavity. Thus, extensive studies have been conducted to develop novel pharmaceutical formulations for effective buccal drug delivery. Various buccal dosage forms such as tablets, gels, and patches/films are now commercially available and have demonstrated high patient compliance. Recently, several manufacturing companies have launched new buccal drug delivery systems such as aerosol, sprays, and particulate systems and they have actively been investigated by numerous pharmaceutical scientists. If the successful development of such systems could be achieved, buccal drug delivery systems would be one of the most promising technology in the near future. In this review, we described the recent development of buccal dosage forms, anatomy of buccal mucosa, drug transport mechanisms, and formulation strategies to enhance the drug permeation through the buccal mucosa.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA) Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Similar content being viewed by others

research articles on buccal drug delivery system

Buccal Delivery of Nanoparticles

research articles on buccal drug delivery system

Buccal/Sublingual Drug Delivery for the Paediatric Population

Buccal dosage forms: general considerations for pediatric patients.

Abd-Elbary A, El-Laithy HM, Tadros MI (2008) Sucrose stearate-based proniosome-derived niosomes for the nebulisable delivery of cromolyn sodium. Int J Pharm 357:189–198

Article   CAS   PubMed   Google Scholar  

Abruzzo A, Cerchiara T, Bigucci F, Gallucci MC, Luppi B (2015) Mucoadhesive buccal tablets based on chitosan/gelatin microparticles for delivery of propranolol hydrochloride. J Pharm Sci 104:4365–4372

Adhikari SNR, Nayak BS, Nayak AK, Mohanty B (2010) Formulation and evaluation of buccal patches for delivery of atenolol. AAPS PharmSciTech 11:1038–1044

Article   CAS   PubMed   PubMed Central   Google Scholar  

Ali J, Khar R, Ahuja A, Kalra R (2002) Buccoadhesive erodible disk for treatment of oro-dental infections: design and characterisation. Int J Pharm 238:93–103

Ameye D, Voorspoels J, Foreman P, Tsai J, Richardson P, Geresh S, Remon JP (2002) Ex vivo bioadhesion and in vivo testosterone bioavailability study of different bioadhesive formulations based on starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures. J Control Release 79:173–182

Ammara HO, Ghorabb M, El-Nahhasc SA, Higazya IM (2011) Proniosomes as a carrier system for transdermal delivery of tenoxicam. Pharmceut Naotech 405:142–152

Google Scholar  

Amores S, Domenech J, Colom H, Calpena AC, Clares B, Gimeno A, Lauroba J (2014) An improved cryopreservation method for porcine buccal mucosa in ex vivo drug permeation studies using Franz diffusion cells. Eur J Pharm Sci 60:49–54

Andrews GP, Laverty TP, Jones DS (2009) Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 71:505–518

Artusi M, Santi P, Colombo P, Junginger HE (2003) Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies. Int J Pharm 250:203–213

Attai MA, EI-Gibaly I, Shaltout SE, Feith GN (2004) Transbuccal permeation, anti-inflammatory activity and clinical efficacy of piroxicam formulated in different gels. Int J Pharm 276:11–28

Article   CAS   Google Scholar  

Aungst BJ (2012) Absorption enhancers: applications and advances. AAPS J 14:10–18

Ayensu I, Mitchell JC, Boateng JS (2012) Effect of membrane dialysis on characteristics of lyophilised chitosan wafers for potential buccal delivery of proteins. Int J Biol Macromol 50:905–909

Azim E, Abd H, Nafee N, Ramadan A, Khalafallah N (2015) Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins. Int J Pharm 488:78–85

Baoteng JS, Mitchell JC, Pawar H, Ayensu I (2014) Functional characterisation and permeation studies of lyophilised thiolated chitosan xerogels for buccal delivery of insulin. Protein Pept Lett 21:1163–1175

Bayrak Z, Tas C, Tasdemir U, Erol H, Ozkan CK, Savaser A, Ozkan Y (2011) Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: in vitro and in vivo evaluation. Eur J Pharm Biopharm 78:499–505

Bernkop-Schnürch A, Krauland AH, Leitner VM, Palmberger T (2004) Thiomers: potential excipients for non-invasive peptide delivery systems. Eur J Pharm Biopharm 58:253–263

Article   PubMed   CAS   Google Scholar  

Bernkop-Schnürch A, Weithaler A, Albrecht K, Greimel A (2006) Thiomers: preparation and in vitro evaluation of a mucoadhesive nanoparticulate drug delivery system. Int J Pharm 317:76–81

Bhardwaj N, Kundu SC (2010) Electrospinning: a fascinating fiber fabrication technique. Biotechnol Adv 28:325–347

Bhati R, Nagrajan RK (2012) A detailed review on oral mucosal drug delivery system. Int J Pharm Sci Res 3:659–681

CAS   Google Scholar  

Bird AP, Faltinek JR, Shojaei AH (2001) Transbuccal peptide delivery: stability and in vitro permeation studies on endomorphine-1. J Control Release 73:31–36

Birudaraj R, Mahalingam R, Li X, Bhaskara RJ (2005) Advances in buccal drug delivery. Crit Rev Ther Drug Carrier Syst 22:295–330

Boateng JS, Areago D (2014) Composite Sodium Alginate and Chitosan Based Wafers for Buccal Delivery of Macromolecules. Austin J Anal Pharm Chem 5:1022

Boateng JS, Ayensu I (2014) Preparation and characterization of laminated thiolated chitosan-based freeze-dried wafers for potential buccal delivery of macromolecules. Drug Dev Ind Pharm 40:611–618

Boateng JS, Matthews KH, Stevens HNE, Eccleston GM (2008) Wound healing dressings and drug delivery systems: a review. J Pharmaceut Sci 97:2892–2923

Boateng JS, Auffret AD, Matthews KH, Humphrey MJ, Stevens HNE, Eccleston GM (2010) Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces. Int J Pharmaceut 389:24–31

Boddupalli BM, Mohammad ZNK, Nath RA, Banji D (2010) Mucoadhesive drug delivery system an overview. J Adv Pharm Tech Res 1:381–387

Bonferoni MC, Sandri G, Rossi S, Ferrari F, Caramella C (2009) Chitosan and its salts for mucosal and transmucosal delivery. Expert Opin Drug Deliv 6:923–939

Boyapally H, Nukala RK, Bhujbal P, Douroumis D (2010) Controlled release from directly compressible theophylline buccal tablets. Colloids Surfaces B Biointerfaces 77:227–233

Campisi G, Giannola LI, Florena AM, De Caro V, Schumacher A, Göttsche T, Paderni C, Wolff A (2010) Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: a trial on pigs. J. Control. Release 145:214–220

Caon T, Jin L, Simões CMO, Norton RS, Nicolazzo JA (2014) Enhancing the buccal mucosal delivery of peptide and protein therapeutics. Pharm Res. doi: 10.1007/s11095-014-1485-1

PubMed   Google Scholar  

Cavallari C, Brigidi P, Fini A (2015) Ex-vivoand in vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base. Int J Pharm 496:593–600

Caviglioli G, Baldassari S, Cirrincione P, Russo E, Parodi B, Gatti P, Drava G (2013) An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose. Int J Pharmaceut 458:74–82

Cid YP, Pedrazzi V, Pereira de Sousa V, Pierre MBR (2012) In Vitro Characterization of Chitosan Gels for Buccal Delivery of Celecoxib: influence of a Penetration Enhancer. AAPS Pharm Sci Tech 13:101–111

Cilurzo F, Gennari CG, Selmin F, Vistoli G (2010) Effects of metal ions on enterosoluble poly(methacrylic acid-methyl methacrylate) coating: a combined analysis by ATR-FTIR spectroscopy and computational approaches. Mol Pharm 7:421–430

Colonna C, Ida Ida Genta, Perugini P, Pavanetto F, Modena T, Valli M, Muzzarelli C, Conti B (2006) 5-methyl-pyrrolidinone chitosan films as carriers for buccal administration of proteins. AAPS Pharm Sci Tech 7:E107–E113

Article   Google Scholar  

Consuelo ID, Jacques Y, Pizzolato G, Guy RH, Falson F (2005) Comparison of the lipid composition of porcine buccal and esophageal permeability barriers. Arch Oral Biol 50:981–987

Cui Z, Mumper RJ (2002) Bilayer films for mucosal (genetic) immunization via the buccal route in rabbits Pharm. Res 19:947–953

Cui F, He C, He M, Tang C, Yin L, Qian F (2008) Preparation and evaluation of chitosan-ethylenediaminetetraacetic acid hydrogel films for the mucoadhesive transbuccal delivery of insulin. J Biomed Mat Res Part A 89:1063–1071

DeGrande G, Benes L, Horrière F, Karsenty H, Lacoste C, McQuinn R, Guo JH, Scherrer R (1996) Specialized oral mucosal drug delivery systems: Patches. In: Rathbone MJ (ed) oral mucosal drug delivery. Marcel Dekker, New York, pp 285–317

Discher DE, Ortiz V, Srinivas G, Klein ML, Kim Y, Christian D, Cai S, Photos P, Ahmed F (2007) Emerging applications of polymersomes in delivery: from molecular dynamics to shrinkage of tumors. Prog Polym Sci 32:838–857

Du JD, Liu Q, Salentinig S, Nguyen TH, Boyd BJ (2014) A novel approach to enhance the mucoadhesion of lipid drug nanocarriers for improved drug delivery to the buccal mucosa. Int J Pharm 471:358–365

Dyawanapelly S, Koli U, Dharamdasani V, Jain R, Dandekar P (2016) Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins. Drug Deliv Transl Res 6:365–379

CAS   PubMed   Google Scholar  

El-Alim abd SH, Kassem AA, Basha M (2014) Proniosomes as a novel drug carrier system for buccal delivery of benzocaine. J Drug Del Sci Tech 24:452–458

El-Samaligy MS, Afifi NN, Mahmoud EA (2006) Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. Int J Pharm 308:140–148

Emami J, Shetabboushehri MA, Varshosaz J, Eisaei A (2013) Preparation and characterization of a sustained release buccoadhesive system for delivery of terbutaline sulfate. Res Pharm Sci 8:219–231

CAS   PubMed   PubMed Central   Google Scholar  

Fernandez-Campos F, Calpena-Campmany AC, Rodriguez-Delgado G, Lopez-Serrano O, Clares-Naveros B (2012) Development and characterization of a novel nystatin-loaded nanoemulsion for the buccal treatment of candidosis: ultrastructural effects and release studies. J Pharm Sci 101:3739–3752

Geresh S, Gdalevsky GY, Gilboa I, Voorspoels J, Remon JP, Kost J (2004) Bioadhesive grafted copolymers as platforms for peroral drug delivery: a study of theophylline release. J. Control. Release 94:391–399

Gilhotra MR, Ikram M, Srivastava S, Gilhotra N (2014) A clinical perspective on mucoadhesive buccal drug delivery systems. Biomed Res 28:81–97

Giovino C, Ayensu I, Tetteh J, Boateng JS (2012) Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules. Int J Pharm 428:143–151

Giovino C, Ayensu I, Tetteh J, Boateng JS (2013) An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. Colloids Surfaces B Biointerfaces 112:9–15

Giunchedi P, Juliano C, Gavini E, Cossu M, Sorrenti M (2002) Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres. Eur J Pharm Biopharm 53:233–239

Graciano TB, Coutinho TS, Cressoni CB, Freitas Cde P, Pierre MB, Pereira SA, Shimano MM, Frange RC, Garcia MT (2015) Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: in vitro and in vivo studies. Photodiagnosis Photodyn Ther 12:98–107

Guo C, Wang J, Cao F, Lee RJ, Zhai G (2010) Lyotropic liquid crystal systems in drug delivery. Drug Discov Today 15:1032–1040

Han RY, Fang JY, Sung KC, Hu OYP (1999) Mucoadhesive buccal disks for novel nalbuphine prodrug controlled delivery: effect of formulation variables on drug release and mucoadhesive performance. Int J Pharm 177:201–209

Hao J, Heng PWS (2003) Buccal delivery systems. Drug Dev Ind Pharm 29:821–832

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

Hazzah HA, Farid RM, Nasra MM, El-Massik MA, Abdallah OY (2015) Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: development and characterization. Int J Pharm 492:248–257

Hearnden V, Sankar V, Hull K, Juras DV, Greenberg M, Kerr AR, Lockhart PB, Patton LL, Porter S, Thornhill MH (2012) New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev 64:16–28

Heinemann L, Jacques Y (2009) Oral Insulin and Buccal Insulin. J Diabetes Sci and Tech 3:568–584

Holm R, Meng-Lund E, Andersen MB, Jespersen ML, Karlsson JJ, Garmer M, Jorgensen EB, Jacobsen J (2013) In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Gottingen minipigs. Eur J Pharm Sci 49:117–124

Holpuch AS, Hummel GJ, Tong M, Seghi GA, Pei P, Russell PM, Mumper J, Mallery SR (2010) Nanoparticles for local drug delivery to the oral mucosa. Pharm Res 27:1224–1236

Jaipal A, Pandey MM, Abhishek A, Vinay S, Charde SY (2013) Interaction of calcium sulfate with xanthan gum: effect on in vitro bioadhesion and drug release behavior from xanthan gum based buccal discs of buspirone. Colloids Surfaces B Biointerfaces 111:644–650

Jaipal A, Pandey MM, Charde SY, Raut PP, Prasanth KV, Prasad RG (2015) Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: in-vitro and in vivo pharmacokinetic studies. J Saudi Pharm 23:315–326

Jankowska AK, Waszkiel D, Kowalczyk A (2007) Saliva as a main component of oral cavity ecosystem Part I. Secretion and function. Wiad Lek 60:148–154

Jelvehgari M, Valizadeh H, Jalali Motlagh R, Montazam H (2014) Formulation and physicochemical characterization of buccoadhesive microspheres containing diclofenac sodium. Adv Pharm Bull 4:295–301

Jiao Y, Pang X, Liu M, Zhang B, Li L, Zhai G (2016) Recent progresses in bioadhesive microspheres via transmucosal administration. Colloids Surfaces B Biointerfaces 140:361–372

Johnston (2015) Anatomy and physiology of the oral mucosa. In: Rathbone MJ, Senel S, Pather I (eds) Oral mucosa rug delivery and therapy, Springer, New York, p 1–16

Jug M, Bećirević-Laćan M, Bengez S (2009) Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol. Drug Dev Ind Pharm 35:796–807

Kaur A, Kaur G (2012) Mucoadhesive buccal patches based on interpolymer complexes of chitosan-pectin for delivery of carvedilol. J Saudi Pharm 20:21–27

Keegan GM, Smart JD, Ingram MJ, Barnes LM, Burnett GR, Rees GD (2012) Chitosan microparticles for the controlled delivery of fluoride. J Dent 40:229–240

Khan S, Gajbhiye C, Singhavi DJ, Yeole P (2012) In situ gel of metoprolol tartrate: physicochemical characterization, in vitro diffusion and histological studies. Indian J Pharmaceut Sci 74:564–570

Kianfar F, Chowdhry BZ, Antonijevic MD, Boateng JS (2012) Novel films for drug delivery via the buccal mucosa using model soluble and insoluble drugs. Drug Dev Ind Pharm 38:1207–1220

Kimura T, Yamano H, Tanaka A, Ueda M, Ogawara K, Higaki K (2002) Transport of d -glucose across cultured stratified cell layer of human oral mucosal cells. J Pharm Pharmacol 54:213–219

Kockisch S, Rees GD, Young SA, Tsibouklis J, Smart JD (2003) Polymeric microspheres for drug delivery to the oral cavity: an in vitro evaluation of mucoadhesive potential. J Pharm Sci 92:1614–1623

Kockisch S, Rees GD, Young SA, Tsibouklis J, Smart JD (2004) In situ evaluation of drug-loaded microspheres on a mucosal surface under dynamic test conditions. Int J Pharm 276:51–58

Kragelund C, Hansen C, Torpet LA, Nauntofte B, Brosen K, Pedersen AML, Buchwald C, Therkildsen MH, Reibel J (2008) Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands. Oral Dis 14:533–540

Kulkarni U, Mahalingam R, Pather SI, Li X, Jasti B (2010) Porcine buccal mucosa as an in vitro model: effect of biological and experimental variables. J Pharm Sci 99:1265–1277

Kumria R, Gupta V, Bansal S, Wadhw J, Nair AB (2013) Oral buccoadhesive films of ondansetron: development and evaluation. Int J Pharm Invest 3:112–118

Kurosaki Y, Yano K, Kimura T (1998) Perfusion cells for studying regional variation in oral mucosal permeability in humans. 2. A specialized transport mechanism in d -glucose absorption across cultured dorsum of tongue. J Pharm Sci 87:613–615

Laffleur F, Zilio M, Menzel C, Lupo N, Schumtzler M (2016) Design, modification and in vitro evaluation of pectin’s bucco-adhesiveness. Ther Deliv 7:369–375

Langoth N, Bernkop-Schnurch A, Kurka P (2005) The inhibitory effect of glutathione on buccal enzymatic degradation of therapeutic peptides (leu-enkephalin, luteinizing hormone-releasing hormone and pituitary adenylate cyclase activating peptide). J Drug Deliv Sci Technol 15:435–438

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

Lankalapalli S, Tenneti VKVS (2015) Formulation and Evaluation of Rifampicin Liposomes for Buccal Drug Delivery. Curr Drug Deliv [Epub ahead of print]

Lassmann-Vague V, Raccah D (2006) Alternatives routes of insulin delivery. Diabetes and metabolism 32:513–522

Lee J, Kellaway IW (2000) Buccal permeation of (D-Ala2, DLeu5) enkephalin from liquid crystalline phases of glyceryl monooleate. Int J Pharm 195:35–38

Lee JW, Park JH, Robinson JR (2000) Bioadhesive-based dosage forms: the next generation. J Pharm Sci 89:850–866

Lefnaoui S, Moulai-Mostefa N (2011) Formulation and in vitro evaluation of k-carrageenan pregelatinized starch-based mucoadhesive gels containing miconazole. Starch 63:512–521

Lei W, Yu C, Lin H, Zhou X (2013) Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo. Asian J Pharm Sci 8:336–345

Li B, Robinson JR (2005) Preclinical assessment of oral mucosal drug delivery systems. In: Ghosh TK, Pfister WR (eds) Drug delivery to the oral cavity: molecules to market. CRC Press, Boca Raton, pp 41–46

Li X, Ye Z, Wang J, Fan C, Pan A (2016) Mucoadhesive buccal films of tramadol for effective pain management. B J Anesthes. doi: 10.1016/j.bjane.2015.08.016

Lu X, Wang C, Wei Y (2009) One-dimensional composite nanomaterials: synthesis by electrospinning and their applications. Small 5(21):2349–2370

Ludwig A (2005) The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev 57:1595–1639

Mahalingam R, Ravivarapu H, Redkar S, Li X, Jasti BR (2007) Transbuccal delivery of 5-aza-2′-deoxycytidine: effects of drug concentration, buffer solution, and bile salts on permeation. AAPS Pharm Sci Tech 8:E1–E5

Makky AMA, El-Gendi NAH, El-Menshawe SF, El-Akkad YE (2012) A buccoadhesive disc as a novel drug delivery system of tenoxicam: formulation and in vitro/in vivo evaluation. J Drug Deliv Sci Technol 22:145–152

Malinová L, Stolínová M, Lubasová D, Martinová L, Brožek J (2013) Electrospinning of polyesteramides based on ε-caprolactam and ε-caprolactone from Solution. Eur Polym. J 49:3135–3143

Mansuri S, Kesharwani P, Jain K, Tekade RK, Jain NK (2016) Mucoadhesion: a promising approach in drug delivery system. React Func Poly 100:151–172

Mao S, Cun D, Kawashima Y (2009) Novel non-injectable formulation approaches of peptides and proteins. In: Jorgensen L, Nielsen HM (eds) Delivery technologies for biopharmaceuticals: peptides, proteins, nucleic Acids and vaccines. Wiley, New York. doi: 10.1002/9780470688397.ch3

Marschütz MK, Bernkop-Schnürch A (2000) Oral peptide drug delivery: polymer-inhibitor conjugates protecting insulin from enzymatic degradation in vitro. Biomaterials 21:1499–1507

Article   PubMed   Google Scholar  

Marxen E, Carlos M, Marie A, Pedersen L, Jacobsen J (2016) Effect of cryoprotectants for maintaining drug permeability barriers in porcine buccal mucosa. Int J Pharm 511:599–605

Masek J, Lubasova D, Lukac R, Turanek-Knotigova P, Kulich P, Plockova J, Maskova E, Prochazka L, Koudelka S, Sasithorn N, Gombos J, Bartheldyova E, Hubatka F, Raska M, Miller AD, Turanek J (2016) Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles-important step towards effective mucosal vaccines. J Control Release. doi: 10.1016/j.jconrel.2016.07.036

Mazzarino L, Borsali R, Lemos-Senna E (2014) Mucoadhesive films containing chitosan-coated nanoparticles: a new strategy for buccal curcumin release. J Pharm Sci 103:3764–3771

McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, Martland T, Berry K, Collier J, Smith S, Choonara I (2005) Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomized controlled trial. Lancet 366:205–210

Modi G, Mihic M, Lewin A (2002) Evolving role of oral insulin in the treatment of diabetes using a novel rapidmist system. Diabetes Metab Res Rev 18:38–42

Montenegro-Nicolini M, Morales OJ (2016) Overview and future potential of buccal mucoadheisve films as drug delivery systems for biologics. AAPS Pharm Sci Tech. doi: 10.1208/s12249-016-0525-z

Monti D, Burgalassi S, Rossato MS, Albertini B, Passerini N, Rodriguez L, Chetoni P (2010) Poloxamer 407 microspheres for orotransmucosal drug delivery. Part II: in vitro/in vivo evaluation. Int J Pharm 400:32–36

Morales JO, McConville JT (2014) Novel strategies for the buccal delivery of macromolecules. Drug Dev Ind Pharm 40:579–590

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

Morrow DIJ, McCarron PA, Woolfson AD, Juzenas P, Juzeniene A, Iani W, Moan J, Donnelty RF (2010) Novel patches based system for localized delivery of ALA esters. J Photochem Photobiol 101:58–69

Munasur AP, Pillay V, Chetty DJ, Govender T (2006) Statistical optimisation of the mucoadhesivity and characterisation of multipolymeric propranolol matrices for buccal therapy. Int J Pharm 323:43–51

Mundargi RC, Rangaswamy V, Aminabhavi TM (2011a) Poly(Nvinylcaprolactam-co methacrylic acid) hydrogel microparticles for oral insulin delivery. J Microencapsul 28:384–394

Mundargi RC, Vidhya R, Aminabhavi TM (2011b) pH-sensitive oral insulin delivery systems using Eudragit microspheres. Drug Dev Ind Pharm 37:977–985

Muzib YI, Kumari KS (2011) Mucoadhesive buccal films of glibenclamide: development and evaluation. Int J Pharm Investig 1:42–47

Article   PubMed   PubMed Central   CAS   Google Scholar  

Mylangam CK, Beeravelli S, Medikonda J, Pidaparthi JS, Kolapalli VRM (2016) Badam gum: a natural polymer in mucoadhesive drug delivery. Design, optimization, and biopharmaceutical evaluation of badam gum-based metoprolol succinate buccoadhesive tablets. Drug Deliv 23:195–206

Nafee N, Ismail F, Boraie N, Mortada L (2003) Mucoadhesive buccal patches of miconazole nitrare. In vitro/in vivo performance and effect of ageing. Int J Pharm 264:1–14

Nappinnai M, Chandanbala R, Balaijirajan R (2008) Formulation and evaluation of nitrendipine buccal films. Indian J Pharm Sci 70:631–635

Naz K, Shahnaz G, Ahmed N, Qureshi NA, Sarwar HS, Imran M, Khan GM (2016) Formulation and In Vitro Characterization of Thiolated Buccoadhesive Film of Fluconazole. AAPS Pharm Sci Tech. doi: 10.1208/s12249-016-0607-y

Nicolazzo JA, Finnin BC (2008) In vivo and in vitro models for assessing drug absorption across the buccal mucosa. In: Ehrhardt C, Kim KJ (eds) Drug absorption studies—in situ, in vitro, and in silico models. Springer, New York, pp 89–111

Chapter   Google Scholar  

Nicolazzo JA, Reed BL, Finnin BC (2004) Assessment of the effects of sodium dodecyl sulfate on the buccal permeability of caffeine and estradiol. J Pharm Sci 93:431–440

Oh DH, Chun KH, Jeon SO, Kang JW, Lee S (2011) Enhanced tranbuccal salmon calcitonin (Sct) delivery: effect of chemical enhancers and electrical assistance on in vitro Sct buccal permeation. Eur J Pharm Biopharm 79:357–363

Oyama Y, Yamano H, Ohkuma A, Ogawara K, Higaki K, Kimura T (1999) Carriermediated transport systems for glucose in mucosal cells of the human oral cavity. J Pharm Sci 88:830–834

Palermo A, Napoli N, Manfrini S, Lauria A, Strollo R, Pozzili P (2011) Buccal spray insulin in subjects with impaired glucose tolerance: the prevoral study. Diabs Obes Meta 13:42–46

Park K, Kwon IC, Park K (2011) Oral protein delivery: current status and future prospect. React Funct Polym 71:280–287

Patel VM, Prajapati BG, Patel MM (2007) Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride. AAPS Pharm Sci Tech 8:E147–E154

Patel VF, Liu F, Brown MB (2011) Advances in oral transmucosal drug delivery. J Control Release 153:106–116

Patel VF, Liu F, Brown MB (2012) Modeling the oral cavity: in vitro and in vivo evaluations of buccal drug delivery systems. J Control Release 161:746–756

Pathak MK, Chhabra G, Pathak K (2013) Design and development of a novel pH triggered nanoemulsified in situ ophthalmic gel of fluconazole: ex vivo transcorneal permeation, corneal toxicity and irritation testing. Drug Dev Ind Pharm 39:780–790

Pather SI, Rathbone MJ, Senel S (2008) Current status and the future of buccal drug delivery systems. Expert Opin Drug Deliv 5:531–542

Peh KK, Wong CF (1999) Polymeric films as a vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Pharm Sci 2:53–61

Pendekal SM, Tegginamat KP (2012) Formulation and evaluation of a bioadhesive patch for buccal delivery of tizanidine. Acta Pharm Sin B 2:318–324

Perioli L, Pagano C (2013) Preformulation studies of mucoadhesive tablets for carbamazepine sublingual administration. Colloid Surf B Biointerfaces 102:915–922

Petelin M, Šentjurc M, Stolič Z, Skalerič U (1998) EPR study of mucoadhesive ointments for delivery of liposomes into the oral mucosa. Int J Pharm 173:193–202

Petelin M, Pavlica Z, Bizimoska S, Šentjurc M (2004) In vivo study of different ointments for drug delivery into oral mucosa by EPR oximetry. Int J Pharm 270:83–91

Phan S, Fong WK, Kirby N, Hanley T, Boyd BJ (2011) Evaluating the link between self-assembled mesophase structure and drug release. Int J Pharm 421:176–182

Portero A, Remunan-Lopez C, Nielsen HM (2002) 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 19:169–174

Pozzilli P, Manfrini S, Costanza F, Coppolino G, Cavallo MG, Fioriti E, Modi P (2005) Biokinetics of buccal spray insulin in patients with type 1 diabetes. Metabolism 54:930–934

Puratchikody A, Prasanth VV, Sam TM, Kumar AB (2011) Buccal drug delivery: past, present and future—a review. Int J Drug Del 3:171–184

Rai V, Tan HS, Michniak-Kohn B (2011) Effect of surfactants and pH on naltrexone (NTX) permeation across buccal mucosa. Int J Pharm 411:92–97

Rai VK, Yadav NP, Sinha P, Mishra N, Luqman S, Dwivedi H, Kymonil KM, Saraf SA (2014) Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery. Carbohydr Polym 103:126–133

Rossi S, Sandri G, Caramella CM (2005) Buccal drug delivery: a challenge already won? Drug Discov Today Technol 2:59–65

Russo E, Selmin F, Baldassari S, Gennari CGM, Caviglioli G, Cilurzo F (2016) A focus on mucoadhesive polymers and their application in buccal dosage forms. J Drug Del Sci Tech 32:113–125

Salamat-Miller N, Chittchang M, Johnston TP (2005) The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev 57:1666–1691

Schwarz JC, Pagitsch E, Valenta C (2013) Comparison of ATR-FTIR spectra of porcine vaginal and buccal mucosa with ear skin and penetration analysis of drug and vehicle components into pig ear. Eur J Pharm Sci 50:595–600

Semalty A, Semalty M, Nautiyal U (2010) Formulation and evaluation of mucoadhesive buccal films of enalapril maleate. Indian J Pharm Sci 72:576–581

Şenel S, Hincal AA (2001) Drug permeation enhancement via buccal route: possibilities and limitations. J Control. Release 72:133–144

Shah JC, Sadhale Y, Chilukuri DM (2001) Cubic phase gels as drug delivery systems. Adv Drug Deliv Rev 47:229–250

Sharma GK, Kumar Sharma P, Bansal M (2012) A review on mucoadhesive buccal patch as a novel drug delivery system. Pharm Sci Monit 3:30–38

Shojaei AH (2011) Buccal mucosa as a route for systemic drug delivery: a review epithelium lamina propria structure. J Pharm Pharm Sci 1:15–30

Shojaei A, Li X (1997) Determination of transport route of acyclovir across buccal mucosa. Proc Int Symp Control Release Bioact Mater 24:427–428

Shuwaili AlAH, Rasool BK, Abdulrasool AA (2016) Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline. Eur J Pharm Biopharm 102:101–114

Smart JD (2005) Buccal drug delivery. Expert Opin Drug Deliv 2:507–517

Smart JD, Keegan G (2010) Buccal drug delivery systems. In: Wen H, Park K (eds) Oral controlled realese formulation design and drug delivery. Wiley, New York, pp 169–184

Smart JD, Nantwi PKK, Rogers DJ, Green KL (2002) A quantitative evaluation of radiolabelled lectin retention on oral mucosa in vitro and in vivo. Eur J Pharm Biopharm 53:289–292

Sogias IA, Williams AC, Khutoryanskiy VV (2012) Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen. Int J Pharm 436:602–610

Souza C, Watanabe E, Borgheti-Cardoso LN, De Abreu Fantini MC, Lara MG (2014) Mucoadhesive system formed by liquid crystals for buccal administration of poly(hexamethylene biguanide) hydrochloride. J Pharm Sci 103:3914–3923

Squier CA, Kremer MJ (2001) Biology of oral mucosa and esophagus. J Natl Cancer Inst Monogr 29:7–15

Sudhakar Y, Kuotsu K, Bandyopadhyay AK (2006) Buccal bioadhesive drug delivery—a promising option for orally less efficient drugs. J Control Release 114:15–40

Swarnakar NK, Jain V, Dubey V, Mishra D, Jain NK (2007) Enhanced oromucosal delivery of progesterone via hexosomes. Pharm Res 24:2223–2230

Tsutsumi K, Obata Y, Nagai T, Loftsson T, Takayama K (2002) Buccal absorption of ergotamine tartrate using the bioadhesive tablet system in guinea-pigs. Int J Pharm 238:161–170

Ungphaiboon S, Maitani Y (2001) In vitro permeation studies of triamcinolone acetonide mouthwashes. Int J Pharm 220:111–117

Utoguchi N, Watanabe Y, Suzuki T, Maehara J, Matsumoto Y, Matsumoto M (1997) Carrier-mediated transport of monocarboxylic acids in primary cultured epithelial cells from rabbit oral mucosa. Pharm Res 14:320–324

Utoguchi N, Watanabe Y, Suzuki T, Maehara J, Matsumoto Y, Matsumoto M (1999) Carrier-mediated absorption of salicylic acid from hamster cheek pouch mucosa. J Pharm Sci 88:142–146

Varshosaz J, Dehghan Z (2002) Development and characterization of buccoadhesive nifedipine tablets. Eur J Pharm Biopharm 54:135–141

Venugopalan P, Sapre A, Venkatesan N, Vyas SP (2001) Pelleted bioadhesive polymeric nanoparticles for buccal delivery of insulin: preparation and characterization. Pharmazie 56:217–219

Veuillez F, Kalia YN, Jacques Y, Deshusses J, Buri P (2001) Factors and strategies for improving buccal absorption of peptides. Eur J Pharm Biopharm 51:93–109

Walker GF (2002) Peptidase activity on the surface of the porcine buccal mucosa. Int J Pharm 233:141–147

Xiang J, Fang X, Li X (2002) Transbuccal delivery of 2′,3′-dideoxycytidine: in vitro permeation study and histological investigation. Int J Pharm 231:57–66

Xu H, Huang K, Zhu Y, Gao Q, Wu Q, Tian W (2002) Hypoglycaemic Effect of a novel Insulin buccal formulation on rabbits. Pharmacol Res 46:459–467

Yang TZ, Wang XT, Yan XY, Zhang Q (2002) Phospholipid deformable vesicles for buccal delivery of insulin. Chem Pharm Bull 50:749–753

Yaturu S (2013) Insulin therapies: current and future trends at dawn. W J Diabetes 4:1–7

Yedurkar P, Dhiman MK, Petkar K, Sawant K (2012) Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro, pharmacokinetic and pharmacodynamic investigations. J Microencapsul 29:126–137

Yuksel N, Bayindir ZS, Aksakal E, Ozcelikay AT (2016) In situ niosome forming maltodextrin proniosomes of candesartan cilexetil: in vitro and in vivo evaluations. Int J Biol Macromol 82:453–463

Download references

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1A5A1008958). This work was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2015R1D1A1A02062278). This article does not contain any studies with human and animal subjects performed by any of the authors.

Author information

Authors and affiliations.

College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul, 06974, Republic of Korea

Sonia Barua, Hyeongmin Kim, Kanghee Jo, Chang Won Seo, Tae Jun Park, Kyung Bin Lee, Kyungsoo Oh & Jaehwi Lee

Department of Food Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Jaehwi Lee .

Ethics declarations

Conflict of interest.

The authors S. Barua, H. Kim, K. Jo, C.W. Seo, T.J. Park, K.B. Lee, G. Yun, K. Oh, and J. Lee declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Barua, S., Kim, H., Jo, K. et al. Drug delivery techniques for buccal route: formulation strategies and recent advances in dosage form design. Journal of Pharmaceutical Investigation 46 , 593–613 (2016). https://doi.org/10.1007/s40005-016-0281-9

Download citation

Received : 18 August 2016

Accepted : 04 October 2016

Published : 15 October 2016

Issue Date : December 2016

DOI : https://doi.org/10.1007/s40005-016-0281-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • Buccal delivery
  • Penetration enhancers
  • Bioahesive polymers
  • Enzyme inhibitors
  • Innovative delivery systems
  • Find a journal
  • Publish with us
  • Track your research

IMAGES

  1. (PDF) A BRIEF REVIEW ON BUCCAL DRUG DELIVERY SYSTEM: ADVANTAGES

    research articles on buccal drug delivery system

  2. Buccal drug delivery system, by dr. umesh kumar sharma and shyma m s

    research articles on buccal drug delivery system

  3. Buccal bioadhesive drug delivery system G1ppt

    research articles on buccal drug delivery system

  4. Buccal and sublingual drug delivery system

    research articles on buccal drug delivery system

  5. [PDF] Buccal Drug Delivery System : A

    research articles on buccal drug delivery system

  6. (PDF) Buccal Drug Delivery System and Penetration Enhancer: A Review

    research articles on buccal drug delivery system

VIDEO

  1. Transmucosal Permeability & Formulation Consideration of Buccal Delivery System

  2. Introduction to buccal mucoadhesive drug delivery system I Drug Delivery Systems Chaitali Surve

  3. Novel Drug Delivery Systems (NDDS) Nasopulmonary Drug Delivery Systems Part-1

  4. UNDERSTAND

  5. UNBELIEVABLE!!! HELP, A CROCODILE SLEEPS WITH MY WIFE

  6. Buccal drug delivery systems in Novel drug delivery systems unit 2

COMMENTS

  1. (PDF) Buccal drug delivery system: A review

    This review article is an overview of buccal drug delivery systems encompassing a review of oral mucosa, active ingredient delivered via buccal route by different mucoadhesive formulations.

  2. An Updated Overview of the Emerging Role of Patch and Film-Based Buccal

    Introduction. The buccal region is an attractive site for target-specific delivery of the active (s) on the mucosa for local and/or systemic effect by absorbing through the mucosal membrane barrier covering the oral cavity. In comparison to oral drug delivery, the mucosal lining of the buccal region has a few unique advantages.

  3. A BRIEF REVIEW ON BUCCAL DRUG DELIVERY SYSTEM ...

    Buccal drug delivery system is a novel method of drug delivering system which have various benefits involving oral administration. The duration of placement of the pharmaceutical formulations at ...

  4. A clinical perspective on mucoadhesive buccal drug delivery systems

    Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective.

  5. A review on bioadhesive buccal drug delivery systems: current status of

    Commercial buccal adhesive drug delivery systems . Commercial formulations or formulations in clinical trials, intended for buccal delivery are presented in table 6. Only few formulations are available on market or under clinical evaluations which indicate the difficulty to develop drug delivery systems with clear efficacy and safety profiles.

  6. Mucoadhesive drug delivery system: An overview

    Abstract. Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration ...

  7. BUCCAL DRUG DELIVERY SYSTEM: THE CURRENT INTEREST

    BUCCAL DRUG DELIVERY SYSTEM: THE CURRENT INTEREST. December 2011. International Research Journal of Pharmacy 2 (12) License. CC BY-NC-ND 4.0. Authors: Mitul Patel. Rajiv Gandhi University of ...

  8. An Overview on Various Approaches and Recent Patents on Buccal Drug

    Background: Buccal delivery is an alluring course of organization for fundamental medication conveyance and it leads direct access to the systemic flow through the interior jugular vein sidesteps drugs from the hepatic first-pass digestion gives high bioavailability. Objective: This article aims at buccal medication conveyance by discussing the structure and condition of the oral mucosa and ...

  9. Design of nanoparticle-based systems for the systemic delivery of

    This review will cover the advantages and disadvantages of conventional drug delivery methods, current types of chemotherapies, factors to consider when designing such systems, and areas to be further researched, with a specific focus on the development of novel nanoparticle-based delivery systems for sublingual and buccal delivery routes.

  10. Recent Advancements and Patents on Buccal Drug Delivery Systems: A

    The buccal drug delivery is an influential route to deliver the drug into the body. Here, in this context, various novel approaches that include lipoidal carriers like ethosomes, transferosomes, niosomes etc. and electrospun nanofibers are discussed, with respect to buccal drug delivery. These carriers can be easily incorporated into buccal ...

  11. Buccal Route of Drug Delivery

    Delivery Approaches for Buccal Administration. Numerous conventional and novel drug delivery systems like sprays, liquids (solutions or suspensions), semisolids (hydrogels), and solids such as tablets/lozenges (including lyophilized and bioadhesive) [], chewing gums, and patches/films have been developed for buccal drug delivery, and the research continues to improve drug delivery across the ...

  12. Current status and the future of buccal drug delivery systems

    Abstract. Background: The delivery of drugs through the buccal mucosa has received a great deal of attention over the last two decades, and yet there are not many buccal delivery products available on the market.Objective: This review outlines the advantages and disadvantages of buccal drug delivery, provides a historical perspective and discusses representative developmental and marketed drugs.

  13. Buccal Delivery Systems: Drug Development and Industrial Pharmacy: Vol

    Buccal drug delivery specifically refers to the delivery of drugs within/through buccal mucosa to affect local/systemic pharmacological actions. This review briefly describes advantages and limitations of buccal drug delivery, anatomical structure of oral mucosa, and methodology in evaluating buccal drug delivery system, focusing on physiology ...

  14. Buccal Bioadhesive Drug Delivery Systems and Their Applications

    A buccal bioadhesive drug delivery system has the potential to overcome these problems. This system protects the drug from enzymes in the liver and GI tract. Drugs given by this route show systemic as well as local effects. The aim of this chapter is to cover every aspect of buccal bioadhesive systems.

  15. Drug delivery techniques for buccal route: formulation ...

    The buccal mucosa has been investigated for the local drug therapy and the systemic delivery of potent peptides, proteins, and other small drug molecules that are subjected to hepatic metabolism and enzymatic degradation in the gastrointestinal tract. Being non-invasive, this route is more feasible for the delivery of therapeutic entities than that of invasive or parenteral drug administration ...

  16. Novel and revisited approaches in nanoparticle systems for buccal drug

    The main aim of this review is to give an overview of the current state-of-the-art of the buccal delivery of nanoparticle systems and address the most promising strategies for drug delivery through the buccal mucosa. The nanoparticle buccal formulations in clinical trials or in the market are also addressed. 2.

  17. [Pdf] Buccal Drug Delivery System: an Overview About Dosage Forms and

    The aim of this review is to discuss the potential of buCCal drug delivery and buccal dosage forms and also explore recent studies and in vitro analysesmethodology of buccAl dosage forms. Management of illness through medication is entering a new era in which growing number of novel drug delivery systems are being employed and are available for therapeutic use. Pharmaceutical research and ...

  18. PDF Mucoadhesive Buccal Drug Delivery System: A Review

    REVIEW ARTICLE Am. J. PharmTech Res. 2020; 10(02) ISSN: 2249-3387 Please cite this article as: Budhrani AB et al., Mucoadhesive Buccal Drug Delivery System: A Review . American Journal of PharmTech Research 2020.

  19. RJPT

    Buccal Drug Delivery System: A Review. The buccal region of the oral cavity is an attractive target for administration of the drug of choice, particularly in overcoming deficiencies associated with the latter mode of administration. Problems such as high first-pass metabolism and drug degradation in the gastrointestinal environment can be ...

  20. Current Status of Mucoadhesive Gel Systems for Buccal Drug Delivery

    Background: Buccal drug delivery is a fascinating research field. Gel-based formulations present potent characteristics as buccal systems since they have great physicochemical properties. Methods: Among the various gels, in situ gels are viscous colloidal systems consisting of polymers; when physiological conditions change (pH, temperature, ion activation), they are transformed into the gel ...

  21. A Review on Current status of Buccal drug delivery system

    The main purpose of the present review is to compile the recent literature with special focus on different aspects of Buccal drug delivery system (BDDS) that achieve significance place among novel drug deliveries. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa.

  22. PDF An Overview on Buccal Drug Delivery System

    Buccal mucosa lines the inner cheek and is used to treat local and systemic conditions in the mouth between the upper gums and cheek. Buccal drug delivery has higher patient acceptability than other non-oral routes of drug administration because it is more vascularized and easier to administer and remove dosage.

  23. (PDF) Buccal Drug Delivery System: An Overview About ...

    blood flow and permeability of the oral mucosa makes. it an idea l site of administratio n for the rapid systemic. delivery of a drug in the treatment of pain, seizures and. angina pectoris 5,6 ...