Transmucosal drug delivery systems

Madhav, N.V.S. Semwal, R. Semwal, D.K. Semwal, R.B. Recent trends in oral transmucosal drug delivery systems An emphasis on the soft palatal route. Expert Opin. Drug Deliv. 2012, 9 (6), 629-647. 

Figure 15 Transmucosal fentanyl drug delivery system Actiq .

A bioadhesive hot-melt extruded film for intraoral drug delivery and the processing thereof has been patented.f Applications of these films may be utilized in transmucosal drug delivery or even transder-mal systems. The films may be produced separately and layered after extrusion, or in some cases, a multilayered system may be extruded in one continuous process. Currently on the market is an extruded film device that is utilized as a denture adhesive. This system includes thermoplastic polymers that have a bioadhesive quality when the film is wetted. Before application and wetting, however, this thin film may be held in one s hand and shaped or cut. This device is again produced by a one-step, continuous process using hot-melt extrusion technology. 

Sprays are liquid dosage forms aerosolized into the oral cavity for transmucosal drug delivery. Due to the formation of small droplets upon aerosolization of the liquid, sprays can achieve shorter lag times and a faster onset of action than other liquid formulations. Oral-lyn is a micellar system utilizing a blend of surfactants as permeation enhancers and formulation stabilizers. The product is one application of the RapidMist system patented by Generex Biotechnology Corporation that has also been used to develop products for vaccine delivery, pain management, and weight loss. 

The nitrates are available in various forms (eg, sublingual, transmucosal, translingual spray, and inhalation). Some adverse reactions are a result of the metiiod of administration. For example, sublingual nitroglycerin may cause a local burning or tingling in the oral cavity. However, die patient must be aware that an absence of this effect does not indicate a decrease in the drug s potency. Contact dermatitis may occur from use of die transdermal delivery system. 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

The purpose of this overview chapter is to provide perspectives in the current status and future prospects of controlled release drug delivery. This is accomplished by examining various delivery systems from a mechanistic point of view, exploring applications of these systems, and discussing relevant biopharmaceutical parameters. A major section of this book is devoted to fundamental issues and applications of transdermal and transmucosal delivery systems (Chapter 6,8,17-23). Other developing systems of future potential... 

Transdermal Delivery Systems. Transdermal delivery of drugs over extended periods of time for systemic therapy has received significant attention. The importance and future prospects of this field are further reflected in the section on Transdermal and Transmucosal Delivery Systems (Chapters 17-23). Intact human skin, once thought to be an impermeable barrier, was realized as a potential portal of entry for systemic drug therapy only recently. 

Ilium, L. and Davis, S. (2005) Chitosan as a delivery system for the transmucosal administration of drugs, in Polysaccharides. Structural Diversity and Functional Versatility, 2nd edn (ed. S. Dumitriu), Marcel Dekker Publ., New York, pp. 643-660. 

The number of hot-melt extrusion patents issued for pharmaceutical systems has increased more than sixfold annually since the early 1980s, with the United States, Germany, and Japan leading the field. The field of melt extrusion technology is growing very rapidly and its use to produce films for transmucosal and transder-mal drug delivery applications was presented by McGinity and Repka (10). 

R. Nave, H. Schmitt, L. Popper, Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects. Drug Delivery 20 (2013), p. 216-223. 

However, it is important to note that the system does not actually facilitate oral transmucosal delivery per se, rather it allows rapid release of the drug in the mouth. The drug is then washed down with the saliva for subsequent absorption in the gastrointestinal tract. 

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