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


Figure 3: Mean itraconazole plasma concentration versus time following a single dose of itraconazole bioadhesive extended release (XR) tablet, 100 mg, or Sporanox capsule, 100 mg, in healthy volunteers, n = 8. (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
Based on the poor performance of hydrophilic polymer-based bioadhesive systems in humans, interest has been focused in using hydrophobic polymers. It is perceived that nonswellable polymers, with a hydrophobic polymeric backbone and various hydrophilic functional groups, may improve bioadhesiveness to mucosa. Extensive progress has been made at Spherics, Inc. into the research and development of proprietary hydrophobic polymers (Spheromers), in which oral bioadhesive dosage form approaches have been explored for sustained and targeted delivery, including the following:
  • The mechanisms of Spheromer interactions with mucosal surfaces as well as the design of novel targeting strategies
  • The development of novel bioadhesive controlled release formulations of challenging drugs with improved and reproducible performance in humans.


Figure 4: Percent coefficient of variation (%CV) of Cmax and AUCo-t for itraconazole bioadhesive extended release tablet, 100 mg, compared with Sporanox capsule, 100 mg, in healthy volunteers, n = 8. (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
Animal studies have been performed with bioadhesive oral delivery systems based on bioerodible Spheromers of the polyanhydride type (34). Among the various thermoplastic polymers studied, poly(fumaric-co-sebacic) (p[FA:SA] in a 20:80 ratio) had the most bioadhesive characteristics. In vivo radiographic transit studies in fasted beagle dogs on bioadhesive-coated, barium sulfate–loaded microspheres showed that the microspheres remained in the stomach and intestine longer than microspheres made of non-bioadhesive polymers (Eudragit RS 100), clearly demonstrating that strong adhesive interactions delayed the passage of microspheres through the GIT (see Figure 2).


Figure 5: Plasma levodopa profiles following a single dose administration of levodopa-carbidopa bioadhesive extended-release (XR) tablets and Sinemet CR tablet in fed beagles (n = 6). Both tablets contain 200 mg levodopa and 50 mg carbidopa (35). (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
Bioadhesive extended-release formulation of drugs with narrow absorption windows and erratic absorption behavior have been developed using Spheromers to increase the residence time in the stomach and to allow drug release downstream in the small intestine in a controlled manner. Using itraconazole as a model drug, bioadhesive extended-release formulations were assessed for their pharmacokinetic performance in healthy volunteers (see Figure 3). Bioadhesive extended-release formulations provided an improved bioavailability compared with the immediate-release Sporanox capsule, while maintaining effective itraconazole plasma levels for more than 24 h and reducing intersubject variability (see Figure 4). A reduction in Cmax is critical to product performance because side effects are associated with peak itraconazole plasma levels (68). These results may help prevent the risk of developing a fungal infection, especially in immunosuppressed patients.


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