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In Vivo Evaluation of an Oral Salmon Calcitonin-Delivery System Based on a Thiolated Chitosan Carrier Matrix

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Abstract

Purpose. To develop and evaluate an oral delivery system for salmon calcitonin.

Methods. 2-Iminothiolane was covalently bound to chitosan in order to improve the mucoadhesive and cohesive properties of the polymer. The resulting chitosan-TBA conjugate (chitosan-4-thiobutylamidine conjugate) was homogenized with salmon calcitonin, mannitol, and a chitosan-Bowman-Birk inhibitor conjugate and a chitosan-elastatinal conjugate (6.75 + 0.25 + 1 + 1 + 1). Optionally 0.5% (m/m) reduced glutathione, used as permeation mediator, was added. Each mixture was compressed to 2 mg microtablets and enteric coated with a polymethacrylate. Biofeedback studies were performed in rats by oral administration of the delivery system and determination of the decrease in plasma calcium level as a function of time.

Results. Test formulations led to a significant (p < 0.005) decrease in the plasma calcium level of the dosed animals in comparison to control tablets being based on unmodified chitosan. The addition of glutathione in the tablets led to a further improvement in the oral bioavailability of salmon calcitonin with an earlier onset of action and a decrease in the calcium level of about 10% for at least 10 h.

Conclusions. The combination of mucoadhesive thiolated chitosan, chitosan-enzyme-inhibitor conjugates and the permeation mediator glutathione seems to represent a promising strategy for the oral delivery of salmon calcitonin.

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Authors and Affiliations

  1. Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria

    Davide Guggi, Constantia E. Kast & Andreas Bernkop-Schnürch

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  1. Davide Guggi
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  2. Constantia E. Kast
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  3. Andreas Bernkop-Schnürch
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Correspondence to Andreas Bernkop-Schnürch.

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Guggi, D., Kast, C.E. & Bernkop-Schnürch, A. In Vivo Evaluation of an Oral Salmon Calcitonin-Delivery System Based on a Thiolated Chitosan Carrier Matrix. Pharm Res 20, 1989–1994 (2003). https://doi.org/10.1023/B:PHAM.0000008047.82334.7d

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  • DOI: https://doi.org/10.1023/B:PHAM.0000008047.82334.7d

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