Amorphous Polymeric Drug Salts as Ionic Solid Dispersion Forms of Ciprofloxacin.

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TitreAmorphous Polymeric Drug Salts as Ionic Solid Dispersion Forms of Ciprofloxacin.
Type de publicationArticle de revue
AuteurMesallati, Hanah, Umerska, Anita-Monika , Paluch, Krzysztof J, Tajber, Lidia
PaysEtats-Unis
EditeurAmerican Chemical Society
VilleWashington
TypeArticle scientifique dans une revue à comité de lecture
Année2017
LangueAnglais
Date1er Juin 2017
Numéro7
Pagination2209-2223
Volume14
Titre de la revueMolecular pharmaceutics
ISSN1543-8392
Mots-clésamorphous solid dispersion, Ciprofloxacin, PAMPA, polymer, polymeric drug salts, solubility
Résumé en anglais

Ciprofloxacin (CIP) is a poorly soluble drug that also displays poor permeability. Attempts to improve the solubility of this drug to date have largely focused on the formation of crystalline salts and metal complexes. The aim of this study was to prepare amorphous solid dispersions (ASDs) by ball milling CIP with various polymers. Following examination of their solid state characteristics and physical stability, the solubility advantage of these ASDs was studied, and their permeability was investigated via parallel artificial membrane permeability assay (PAMPA). Finally, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the ASDs were compared to those of CIP. It was discovered that acidic polymers, such as Eudragit L100, Eudragit L100-55, Carbopol, and HPMCAS, were necessary for the amorphization of CIP. In each case, the positively charged secondary amine of CIP was found to interact with carboxylate groups in the polymers, forming amorphous polymeric drug salts. Although the ASDs began to crystallize within days under accelerated stability conditions, they remained fully X-ray amorphous following exposure to 90% RH at 25 °C, and demonstrated higher than predicted glass transition temperatures. The solubility of CIP in water and simulated intestinal fluid was also increased by all of the ASDs studied. Unlike a number of other solubility enhancing formulations, the ASDs did not decrease the permeability of the drug. Similarly, no decrease in antibiotic efficacy was observed, and significant improvements in the MIC and MBC of CIP were obtained with ASDs containing HPMCAS-LG and HPMCAS-MG. Therefore, ASDs may be a viable alternative for formulating CIP with improved solubility, bioavailability, and antimicrobial activity.

URL de la noticehttp://okina.univ-angers.fr/publications/ua16076
DOI10.1021/acs.molpharmaceut.7b00039
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http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00039

Titre abrégéMol. Pharm.
Identifiant (ID) PubMed28570079