Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems - Pharmaceutical Technology

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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.


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.


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