News from Europe's pharmaceutical manufacturing industry coupled with upcoming events, and exclusive articles and interviews from industry experts. WEEKLY
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
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.
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
Survey
How does your company apply quality-by-design (QbD) principles to manufacturing processes?
To all processes for both new and legacy products
20%
To all process for new products only
15%
To select process for new products only
24%
To select processes for both new and legacy products
