Transmucosal delivery

Chun IK, Chien YW (1993) Transmucosal delivery of methionine enkephalin. I Solution stability and kinetics of degradation in various rabbit mucosa extracts. J Pharm Sci 82 373-378. 

Sayani, A.P., I.K. Chnn, and Y.W. Chien, Transmucosal delivery of leucine enkephalin stabilization in rabbit enzyme extracts and enhancement of permeation through mucosae. J Pharm Sci, 1993. 82(11) 1179-85. 

A mucoadhesive buccal patch was evaluated for transmucosal delivery of oxytocin (OT) [103], OT was incorporated with coformulations of Carbopol 974P and silicone polymer. The plasma concentrations of OT remained 20- to 28-fold greater than levels obtained from placebo patches for a period of 0.5 to 3.0 h. 

Transmucosal delivery of salmon calcitonin (sCT) via the buccal route was studied using a mucoadhesive bilayer thin-film composite (TFC) [104], In vitro studies showed that over 80% of sCT was released from the TFCs within 240 min. The relative bioavailability for rabbits treated with the film composites was 43.8% + 10.9% as compared to intravenous injection. 

Li, C., et al. 1997. Transmucosal delivery of oxytocin to rabbits using a mucoadhesive buccal patch. Pharm Dev Technol 2 265. 

Cui, Z., and R.J. Mumper. 2002. Buccal transmucosal delivery of calcitonin in rabbits using thin-film composites. Pharm Res 19 1901. 

Chien, Y.W. 1995. Biopharmaceutics basis for transmucosal delivery. STP Pharma Sci 5 718. 

Iontophoresis techniques (i.e., the use of electric current to facilitate transdermal delivery) have also been advocated as a way to enhance transdermal opioid delivery to the systemic circulation.11 By varying the amount of electric current, iontophoresis may ultimately allow the patient to control the rate of transdermal administration of the opioid.10,76,78 Finally, certain opioids such as fentanyl can be administered systemically via lozenges or a lollipop that dissolves in the mouth (transmucosal delivery), or via nasal spray (intranasal administration).21,54 It will be interesting to see if these newer methods of administration will gain widespread acceptance in the future. 

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. 

Ingestion and initial fragmentation of food occurs in the oral cavity. There has recently been considerable interest in this site for the systemic delivery of drag moieties. The possibility of transmucosal delivery via the mucous membranes of the oral cavity is discussed in Chapter 7. 

Localized dmg delivery to the mouth is used for the treatment of conditions of the oral cavity, principally aphthous ulcers, fungal conditions and periodontal disease. However, in addition to topical delivery, there has been considerable interest in the possibility of oral transmucosal delivery in order to achieve the... 

Prochlorperazine fulfils the criteria for efficient transmucosal delivery it is a highly lipid soluble base with a pKa of 8.1 and is therefore largely non-ionized at salivary pH. Because first-pass metabolism is avoided, the bioavailability via the buccal route is much higher than via the oral route (Figure 7.2). 

Recently, adhesive patches have been developed for transmucosal delivery. Such systems are discussed further in Section 7.7. 

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. 

Figure 7.4 Cydot matrix system for the transmucosal delivery of melatonin (Courtesy of 3M Pharmaceuticals)...

M, whose experience in adhesive technology has been put to use in the transdermal field, has similarly built on its adhesive expertise in the development of a proprietary mucosal patch formulation (Cydot), which has demonstrated considerable potential for oral transmucosal delivery. The pill-sized patch uses a new bioadhesive which sticks to the gum, the cheek or the lip without causing irritation and is designed to deliver drugs for short and extended periods (up to 24 h). The small size, 0.5 to 3 cm2, helps patient compliance significantly. 

Figure 7.5 Melatonin kinetics after 10 h diurnal Cydot patch application in 12 healthy subjects. TMD =transmucosal delivery, TDD= transdermal delivery, ORAL-CR=oral controlled release delivery. (Courtesy of 3M Pharmaceuticals)...

The market for oral transmucosal delivery systems is still very small, and its growth over the next five years will depend on the dmgs which are approved for delivery by this route and the prevalence of the conditions for which they are intended. 

Nitroglycerin (NTC) is distinguished by a high membrane penetrability and very low stability. It is the drug of choice in the treatment of angina pectoris attacks. For this purpose, it is administered as a spray, or in sublingual or buccal tablets for transmucosal delivery. The onset of action is between 1 and 3 minutes. Due to a nearly complete presystemic elimination, it is poorly suited for oral administration. Transdermal delivery (nitroglycerin patch) also avoids presystemic elimination. 

These preparations are primarily intended to achieve faster onset of action for drugs such as analgesics, antipyretics, and coronary vasodilators. Other advantages include enhanced oral bioavailability through transmucosal delivery and pregastric absorption,... 

Jay S, Fountain W, Cui Z, Mumper RJ. Transmucosal delivery of testosterone in rabbits using novel bi-layer mucoadhesive wax-film composite disks. / Pharm Sci 2002 91(9) 2016-2025. 

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