Formulation oral transmucosal

Dosages and routes of administration For acute (postoperative) pain and for anesthesia, fentanyl is given by the intravenous route. For pre-medication in anesthesia and for break-through pain the compound can also been given as an oral-transmucosal formulation (Ashburn and Streisand, 1994). A transdermal patch has been developed for chronic pain treatment (Jeal and Benfield, 1997 O Siordin, 1998). The intravenous doses for premedication are 50-100 pg, oral-transmucosal systems contain 200-400 pg and patch formulations have a delivery rate of 25-100 pg/h. 

Formulation factors affecting oral transmucosal bioavailability 175... 

FORMULATION FACTORS AFFECTING ORAL TRANSMUCOSAL BIOAVAILABILITY... 

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. 

An oral transmucosal formulation of etomidate, which is absorbed over 15 minutes, has been studied in 10 healthy adults at four doses 12.5, 25, 50, and 100 mg (25). Dose-related drowsiness and light sleep occurred 10-20 minutes after administration. Peak serum concentrations and clinical effects were noted at about 20 minutes, with no clinical effect noticeable by 60 minutes. There was no vomiting and only four patients had transient nausea. Two patients had brief episodes of involuntary tremor with the 100 mg dose. Of note was the increasingly unpleasant taste with increasing dose and the apparent reduction in absorption with higher doses. 

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. 

If disturbances of gastrointestinal function prevent the use of oral sustained-release morphine, the fentanyl transdermal system (fentanyl patch) can be used over long periods. Furthermore, buccal transmucosal fentanyl can be used for short episodes of breakthrough pain (see Alternative Routes of Administration). Administration of strong opioids by nasal insufflation has been shown to be efficacious, and nasal preparations are now available in some countries. Approval of such formulations in the USA is growing. In addition, stimulant drugs such as the amphetamines have been shown to enhance the analgesic actions of the opioids and thus may be very useful adjuncts in the patient with chronic pain. 

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