Release kinetics and up-take studies of model fluoroquinolones from carbomer hydrogels.
Hydrogels of carbomer (C) loaded with model slightly soluble fluoroquinolone antimicrobials (AMFQ), norfloxacin (I) and ciprofloxacin (II) were prepared to evaluate their physical and delivery properties. Thus, dispersions of 0.25% of C loaded with 0.2-0.5 mol equivalents of AMFQ and 0.2-0.5 mol equivalents of NaOH yielded pseudoplastic hydrogels with a high negative electrokinetic potential and good physical stability. Concentration of AMFQ in the hydrogels was, respectively, 7.2 and 34 times higher than I and II aqueous solubility, indicating a high increase in aqueous compatibility. Release of AMFQ in bicompartimetal Franz type cell occurred by zero order kinetics. Delivery rate constant (k(0)) was five to six times higher as water was replaced by NaCl solution as receptor medium. Release in agar dishes revealed that, even under high dilution, delivery remains modulated. Intestinal absorption flux coefficient in everted rat intestine (k(U)) were measured with reference solutions (RS) of free AMFQ (k(U)(RS) II>k(U)(RS) I) and with hydrogels (H), in which the pattern was reversed since k(U)(H) I>k(U)(H) II. As expected k(U)(H) II was 0.55 times lower than k(U)(RS) II. However, k(U)(H) I was 1.37 times higher than its reference, which cannot be explained from the analysis of k(0) and k(U)(RS) alone. Hydrogels C-AMFQ behave as a reservoir of AMFQ able to deliver it at a constant rate and would be useful to design topical and or systemic dosage forms.
Vilches
A P
AP
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Argentina.
Jimenez-Kairuz
A
A
Alovero
F
F
Olivera
M E
ME
Allemandi
D A
DA
Manzo
R H
RH
D000180:Acrylic Resins; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002939:Ciprofloxacin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003102:Colloids; D015169:Colony Count, Microbial; D004337:Drug Carriers; D004344:Drug Incompatibility; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects; D020100:Hydrogels; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011145:Polyvinyls / Q000737:chemistry*; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D014867:Water / Q000737:chemistry
D000180:Acrylic Resins; D000890:Anti-Infective Agents; D003102:Colloids; D004337:Drug Carriers; D020100:Hydrogels; D011145:Polyvinyls; D014867:Water; C006912:carboxypolymethylene; D002939:Ciprofloxacin; D009643:Norfloxacin