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Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems
Novel hydrophobic bioadhesive polymers and dosage designs are now available to effectively achieve tailored release kinetics of a broad range of drugs to meet the clinical needs.
Nov 2, 2008 By:
Avinash Nangia, PhD Pharmaceutical Technology
Volume 32,
Issue 11,
pp. 100-121
Table II: Pharmacokinetic data for levodopa-carbidopa bioadhesive extended release (XR) tablets and Sinemet CR tablets in
fasted beagles (n = 6). (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
Levodopa-carbidopa was also explored in a bioadhesive oral drug delivery system as an oral dopaminergic treatment strategy
to maintain the system at the target site over an extended duration and provide stable blood levels of drug in advanced Parkinson's
Disease. Figure 5 shows the pharmacokinetic performance of levodopa–carbidopa administered as a bioadhesive, multilayer tablet
to beagle dogs. In comparison with Sinemet controlled-release tablets, this novel bioadhesive extended-release dosage form
resulted in an extended plasma levodopa profile for as long as 12 h and improved bioavailability both in fasting and fed animals
as a result of prolonged residence time (see Tables II and III) (35). By providing a continuous delivery of levodopa at a
constant rate, the system should not only reduce the motor complications related to abnormal intermittent pulsatile dopaminergic
stimulation but also improve patient compliance and quality of life. Figure 6 shows the levodopa profile of bioadhesive extended
release tablets and Sinemet controlled-release tablets in young healthy volunteers. Because the gastroretentive systems are
highly dependent on the calorie content of the meal, both formulations were administered following a light breakfast (approximately
380 calories). The bioadhesive system provides a rapid and reliable levodopa level that is needed to achieve the "morning
kick," followed by a smooth delivery of levodopa over an extended duration. Reduced intersubject variability data showed superior
reproducibility in the in vivo performance compared with the marketed product, Sinemet controlled-release tablets (36).
Table III: Pharmacokinetic data for levodopa-carbidopa bioadhesive extended Release (XR) tablets and Sinemet CR tablets in
fed beagles (n = 6). (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
Figure 7 shows the pharmacokinetic profile of a delayed-release bioadhesive capsule formulation containing 0.375 mg pramipexole
(a dopamine receptor agonist) administered once daily compared with immediate-release Mirapex tablets, 0.125mg, given three
times daily in healthy human volunteers. By allowing the drug to be released in the small intestine, the novel bioadhesive
dosage form extended drug release to 22 h with a similar extent of exposure compared with Mirapax tablets given three times
daily. Also, the bioadhesive formulation showed reduced fluctuations in pramipexole levels and eliminated nausea and vomiting
(37).
Figure 6: Plasma levodopa profiles following a single dose administration of levodopa-carbidopa bioadhesive extended release
(XR) tablets and Sinemet CR tablets in healthy volunteers. Both tablets contain 200 mg levodopa and 50 mg carbidopa, n = 12
(36). (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
These examples cited demonstrate that systems based on hydrophobic bioadhesive polymers are likely to show great promise in
terms of extended residence time and bring new possibilities for controlled delivery of drugs with narrow absorption windows.
Avinash Nangia, PhD, is senior vice-president of research and development at Spherics, Inc., 375 Forbes Blvd., Mansfield, MA 02048, tel. 508.452.7000, fax 508.452.7070.
Articles by Avinash Nangia, PhD
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