Formulation and in vitro-in vivo evaluation of a new compression-coated tablet of amoxicillin/clavulanate and formulation potential of the antimicrobial peptide nisin Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/5q47rs04n

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  • This thesis is compromised of two distinct formulation sections, which are described below: New compression-coated tablet formulations were developed for amoxicillin/clavulanate. Amoxicillin in an outer coat was separated from clavulanic acid in a core tablet by inactive ingredients in a middle coat. A chewable compression-coated tablet formulation with 50% stearic acid in the middle coat showed high clavulanic acid stability in comparison to the marketed traditional tablet formulation. Stearic acid acted as a hydrophobic barrier that prevents passage of moisture through the outer coats into the core and it helped in the bonding of the outer coats to the core because it softens upon compression. The bioavailability of clavulanic acid, however, was reduced which was attributed to the effect of stearic acid. Stearic acid was removed from the formulation of swallow tablets and replaced with Avicel®, consequently, the outer coat did not adhere tightly to the core and tended to cap off, which resulted in low stability of clavulanic acid. In bioavailability studies of the swallow tablets, the two formulations were equivalent to the marketed formulation for amoxicillin, but not for clavulanic acid, which is most likely due to the small sample size studied and high intersubject variation. Nisin, an antimicrobial protein, was evaluated for ability to emulsify oil-in-water using conductivity measurements. In comparison to Tween® 80 and β-casein, nisin showed substantial emulsifying activity. The emulsifying activity was found to be highly concentration- and pH-dependent. Nisin was found to form a gel-like structure at the oil water interface which retarded release of the drug sulfasalazine. Interfacial tension kinetics exhibited by nisin at an oil-water interface were monitored with DuNoy tensiometry. Interfacial pressure kinetics were interpreted with reference to a simple model that allows for a protein to be adsorbed in structurally dissimilar states. The model suggested that nisin's tendency to adapt a more unfolded structure at the oil-water interface increases with decreasing concentration. The effects of nisin on drug release from oil-in-water emulsions, and on erythrocytes were evaluated as well. It was found that nisin retards drug release in emulsions and lyses red blood cells.
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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2012-09-04T21:33:32Z (GMT) No. of bitstreams: 1 BaniJaberAhmadKh1999.pdf: 6775114 bytes, checksum: 151c25f997f81da0f196e98cb5fe0388 (MD5)
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