Send Orders for Reprints to [email protected] 26 Drug Delivery Letters, 2014, 4, 26-37 Transmucosal Drug Delivery- An Overview Pooja Abhang*, Munira Momin, Mayur Inamdar and Swapan Kar Oriental College of Pharmacy, Secctor-2, Sanpada, Navi Mumbai-400705, Maharastra, India Abstract: During the past 20 years, advances in drug formulations and innovative routes of administration have been made. The understanding of drug transport across tissues has increased. The administration of drug by transmucosal routes offers the advantage of being a relatively painless administration and has the potential for greater flexibility in a variety of clinical situations. The transmucosal route includes oral, nasal, vaginal, and urethral and presents a challenge in the field of novel drug delivery technology. The oral transmucosal delivery, especially the buccal and sublingual routes have been explored successfully for a number of drugs in the last few decades with novel approaches emerging continuously. The transmucosal membranes are relatively permeable, have a rich blood flow and hence allow the rapid uptake of a drug into systemic circulation to avoid first pass metabolism. This route of drug delivery offers a number of benefits over other drug delivery approaches and allows drugs to circumvent some of the body’s natural defense mechanisms like first pass me- tabolism, harsh stomach environment etc. Several approaches have been used like drug delivery through the nasal route by using sprays, pumps and gels while the mucoadhesive, quick dissolve tablets and solid lozenge formulations are for the oral mucosal route. Also, vaginal or urethral routes can be explored using mucoadhesive suppositories, in-situ gel and foam etc. The purpose of this review is to compile the basic approach studies by different research groups in the last few years. Keywords: Bioadhesive polymer, drug delivery, mucoadhesion, transmucosal. INTRODUCTION NEED OF TRANSMUCOSAL DRUG DELIVERY Transmucosal delivery of therapeutic agents is a popular There is a need for transmucosal drug delivery for Con- method because mucous membranes are relatively perme- trolled release, for targeted and localized drug delivery, for able, allowing for rapid uptake of a drug into the systemic bypass first pass metabolism, for avoidance of drug degrada- circulation and avoiding the first pass metabolism. This effi- tion, for prolonged effect, for high drug flux through the ab- cient uptake offers several benefits over other methods of sorbing tissue, and for reduction in fluctuation of steady state delivery and allows drugs to circumvent some of the body’s plasma level. natural defense mechanisms. Transmucosal products can be designed to be administered via the nasal route by using An ideal dosage form is one which attains the desired sprays, pumps and gels, via the oral/buccal route using mu- therapeutic concentration of drug in plasma and maintains a coadhesive, quick dissolve tablets and solid lozenge formula- constant for the entire duration of treatment. This is possi- tions and via vaginal or urethral routes using suppositories ble through administration of a conventional dosage form [1]. in a particular dose and at a particular frequency. In most cases, the dosing intervals are much shorter than the half In the development of these drug delivery systems, mu- life of the drug resulting in a number of limitations associ- coadhesion of the device is a key element. The term ‘muco- ated with such a conventional dosage form which is as adhesive’ is commonly used for materials that bind to the follows: mucin layer of a biological membrane. Mucoadhesive poly- mers have been utilized in many different dosage forms in Poor patient compliance; increased chances of missing efforts to achieve systemic delivery of drugs through the the dose of a drug with a short half-life for which frequent different mucosae. These dosage forms include tablets, administration is necessary; a typical peak plasma concentra- patches, tapes, films, semisolids and powders. To serve as tion time profile which makes attainment of a steady state mucoadhesive polymers, the polymers should possess some condition difficult; unavoidable fluctuation in the drug con- general physiochemical features such as predominantly ani- centration that may lead to under medication or over medica- onic hydrophilicity with numerous hydrogen bond-forming tion as the steady state concentration values fall or rise be- groups, suitable surface property for wetting mucus/mucosal yond the therapeutic range; fluctuating drug levels that may tissue surfaces and sufficient flexibility to penetrate the mu- lead to precipitation of adverse effects especially of a drug cus network or tissue crevices [2, 3]. with a small therapeutic index whenever overmedication occurs [4]. *Address correspondence to this author at the Oriental College of Phar- macy, Secctor-2, Sanpada, Navi Mumbai-400705, Maharastra, India; Tel: +91-8108146662; E-mail: [email protected] 2210-304X/14 $58.00+.00 © 2014 Bentham Science Publishers Transmucosal Drug Delivery- An Overview Drug Delivery Letters, 2014, Vol. 4, No. 1 27 ADVANTAGES OF TRANSMUCOSAL DRUG DE- safety margin of high potency drugs due to better con- LIVERY trol of plasma levels, maximum utilization of the drug enabling a reduction in the total amount of drug admin- Advantages of Transmucosal Drug Delivery are Stated as istered, improved patient convenience and compliance Follows: due to less frequent drug administration, reduction in • A prolonged residence time at the site of drug action or fluctuation of steady state levels and therefore better absorption. control of disease conditions and a reduced intensity of local or systemic side effects. • Localization of drug action of the delivery system at a given target site Despite the several advantages associated with oral con- trolled drug delivery systems, there are many limitations [5]. • Ease of administration • Convenient termination of therapy (except through gas- LIMITATIONS OF TRANSMUCOSAL DRUG DELIV- trointestinal route), ERY • Permits localization of the drug to the oral cavity for a Drugs, which irritate the oral mucosa, have a bitter or prolonged period of time unpleasant taste and odour and cannot be administered by • Can be administered to unconscious patients, except this route. Drugs which are unstable at buccal pH cannot be gastrointestinal administered by this route. Only drugs with small dose re- quirements can be administered. Drugs may be swallowed • Offers an excellent route for the systemic delivery of with saliva and lose the advantages of the buccal route. Only drugs with high first pass metabolism, thereby offering a those drugs which are absorbed by passive diffusion can be greater bioavailability, administered by this route. Eating and drinking may become • Facilitation in achieving a significant reduction in dose restricted, however swallowing of the formulation by the thereby reducing dose related side effects, patient may be possible. Over hydration may lead to the for- mation of a slippery surface and the structural integrity of the • Causing drugs which are unstable in the acidic environ- formulation may get disrupted by the swelling and hydration ment to be destroyed by the enzymatic or alkaline envi- of the bioadhesive polymers [6]. ronment of the intestine to be administered by this route. Eg. Buccal, sublingual and vaginal. Drugs which show MECHANISM OF MUCOADHESION poor bioavailability via the oral route can be adminis- tered conveniently The concept of mucoadhesion is one that has the poten- tial to improve the highly variable residence times experi- • Offers a passive system of drug absorption and does not enced by drugs and dosage forms at various sites in the gas- require any activation, trointestinal tract, and consequently, to reduce variability and • The presence of saliva ensures a relatively large amount improve efficacy. Intimate contact with the mucosa should of water for drug dissolution unlike in the case of rectal enhance absorption. The mechanisms responsible in the for- and transdermal routes mation of bioadhesive bonds are not fully known, however most research has described bioadhesive bond formation as a Rapid systemic absorption • three step process: [7, 8]. Provides an alternative for the administration of various • Step 1: Wetting and swelling of the polymer. hormones, narcotic analgesic, steroids, enzymes, cardio- vascular agents, etc Step 2: Interpenetration between the polymer chains and the mucosal membrane. • The buccal mucosa is highly perfused with blood vessels and offers a greater permeability than the skin, with less Step 3: Formation of Chemical bonds between the entangled dosing frequency, shorter treatment period, increased chains. Fig. (1). Wetting and swelling of polymer. 28 Drug Delivery Letters, 2014, Vol. 4, No. 1 Abhang et al. Step 1 The wetting and swelling step occurs when the polymer spreads over the surface of the biological substrate or mu- cosal membrane in order to develop an intimate contact with the substrate. This can be readily achieved for example by placing a bioadhesive formulation such as a tablet or paste within the oral cavity or vagina. Bioadhesives are able to adhere to or bond with biological tissues by the help of the Fig. (3). Entanglement of Polymer and Mucus by Chemical bonds. surface tension and forces that exist at the site of adsorption or contact. Swelling of polymers occurs because the compo- TRANSMUCOSAL ROUTES OF DRUG DELIVERY nents within