Oral transmucosal drug delivery

CURRENT TECHNOLOGIES FOR ORAL TRANSMUCOSAL DRUG DELIVERY... 

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. 

Suitability of Various Regions of the Oral Mucosa for Transmucosal Drug Delivery based on Various Tissue Properties... 

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. 

Buccal mucosal permeability also varies with the anatomical site for example, keratinized sites of the oral cavity hinder the permeation of hydrophilic molecules.96 Therefore, it is important to consider these factors in selecting the transmucosal route for drug delivery in the oral cavity. A limited surface area (100 to 170 cm2) and the need to mask taste for bitter drugs are some of the drawbacks associated with this route of drug delivery. 

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. 

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. 

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. 

Considerable advances have occurred in DDS within the past decade. Extended release, controlled release, and once-a-day medications are available for several commonly used drugs. Global vaccine programs are close to becoming a reality with the use of oral, transmucosal, transcutaneous, and needle-less vaccination. Considerable advances have been made in gene therapy and delivery of protein therapeutics. Many improvements in cancer treatment can be attributed to novel drug delivery technologies. 

The skin is biologically intended to be a barrier. Evading this barrier is not easy, because drugs must traverse dead epithelium and live dermis the former is hydrophobic, while lipophilic drugs tends to form a reservoir in the latter. As in oral transmucosal administration, potent drugs, with modest requirements for mass absorbed and reasonable lipophilicity, are the best candidates for transdermal delivery. Fentanyl, nicotine, and scopolamine are good examples. 

The potential of CBNs has been documented in the arena of fields including immunization, topical/ocular/dermal drug delivery, transmucosal oral/nasal peptide absorption, anti-cancer drug delivery, brain delivery and gene delivery. Figure 4.2 summarizes... 

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. 

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. 

Parenteral administration is not perceived as a problem in the context of drugs which are administered infrequently, or as a once-off dose to a patient. However, in the case of products administered frequently/daily (e.g. insulin to diabetics), non-parenteral delivery routes would be preferred. Such routes would be more convenient, less invasive, less painful and generally would achieve better patient compliance. Alternative potential delivery routes include oral, nasal, transmucosal, transdermal or pulmonary routes. Although such routes have proven possible in the context of many drugs, routine administration of biopharmaceuticals by such means has proven to be technically challenging. Obstacles encountered include their high molecular mass, their susceptibility to enzymatic inactivation and their potential to aggregate. 

One of the key pieces to development of a successful drug product is the ability to deliver the drug to the site of action with minimal discomfort or inconvenience to the patient. For small molecule therapeutics, there is a wide range of options available for drug administration. Delivery via injection (IV, IM, and SC), oral, nasal, ocular, transmucosal (buccal, vaginal, and rectal), and transdermal routes is possible with small molecule drugs. However, the size of proteins and the complexity of their structures severely limit the routes of administration available to proteins. 

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,... 

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