A polymer carrier system for taste masking of macrolide antibiotics.
A polymer carrier system was developed to reduce the bitterness of erythromycin and its 6-O-methyl derivative, clarithromycin, by absorption to Carbopol. The mechanism involves ionic bonding of the amine macrolide to the high molecular weight polyacrylic acid, thereby removing the drug from the solution phase in an ion-free suspension. After ingestion, endogenous cations displace the drug from the polymer in the gastrointestinal tract to achieve bioavailability. The macrolide-Carbopol complexes were prepared by dissolving or slurrying predetermined ratios of drug and polymer in water or hydroalcoholic mixtures. A series of in vitro equilibrium studies, taste screening, and bioavailability studies in dogs established the characteristics for the various drug-polymer ratios. Taste protection was further improved by encapsulating the adsorbate particles with polymer coatings. Hydroxypropyl methylcellulose phthalate (HP-55) provided the best combination of suspension stability, taste protection and bioavailability. Human bioavailability studies demonstrated that the microencapsulated Carbopol absorbates of erythromycin and clarithromycin gave blood levels comparable to those obtained from conventional solid formulations.
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Pharmaceutical Products Division, Abbott Laboratories, North Chicago, Illinois 60064.
Borodkin
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S
Woodward
L
L
Li
P
P
Diesner
C
C
Hernandez
L
L
Vadnere
M
M
D000042:Absorption; D000180:Acrylic Resins; D000818:Animals; D000900:Anti-Bacterial Agents; D001682:Biological Availability; D017291:Clarithromycin; D004285:Dogs; D004337:Drug Carriers; D004917:Erythromycin / Q000031:analogs & derivatives; D006801:Humans; D008747:Methylcellulose / Q000031:analogs & derivatives; D011145:Polyvinyls; D013649:Taste
D000180:Acrylic Resins; D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D011145:Polyvinyls; C006912:carboxypolymethylene; C006903:carbopol 940; D004917:Erythromycin; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D017291:Clarithromycin