Engineered microparticles based on drug-polymer coprecipitates for ocular-controlled delivery of Ciprofloxacin: influence of technological parameters.
Ciprofloxacin is a drug active against a broad spectrum of aerobic Gram-positive and Gram-negative bacteria, for the therapy of ocular infections. It requires frequent administrations owing to rapid ocular clearance and it is a good candidate for ocular controlled release formulations. The preparation of such drug release systems is still a challenge. Ionic interactions between ciprofloxacin and the polyelectrolytes chondroitin sulfate or lambda carrageenan result in coprecipitates that can act as microparticulate controlled release systems from which the drug is released after being displaced by the medium's ions. In some formulations, Carbopol was added to improve the mucoadhesive properties. The aim of this research was the study of the influence of the technological parameters of the preparation method of coprecipitates on their particle size, with the goal of achieving particles engineered with a size suitable for the ocular administration. Technological parameters taken into account were: concentration of drug and polymer solutions utilized for the preparation of interaction products, possible use of surfactants (kind and concentration), temperature of the solutions and stirring during the process of preparation of the coprecipitates. Preliminary stability study tests were carried out to further characterize the leader formulation. Particle size in suspensions for ocular drug delivery is a critical parameter influencing the quality of the formulation. The results obtained from this study show that chondroitin sulfate coprecipitates present the best characteristics in terms of particle size suitable for ocular administration. A further improvement of the particle size characteristics has been obtained with the addition of surfactants.
a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy .
Elisabetta
E
Gavini
b Department of Drug Sciences , University of Pavia , Pavia , Italy , and.
Maria Cristina
MC
Bonferoni
a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy .
Giovanna
G
Rassu
b Department of Drug Sciences , University of Pavia , Pavia , Italy , and.
Giuseppina
G
Sandri
b Department of Drug Sciences , University of Pavia , Pavia , Italy , and.
Silvia
S
Rossi
a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy .
Andrea
A
Salis
c PhD School of Experimental Medicine, University of Pavia , Pavia , Italy.
Elena Piera
EP
Porcu
a Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy .
Paolo
P
Giunchedi
D060433:Administration, Ophthalmic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002616:Chemical Engineering / Q000379:methods*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D008863:Microspheres; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D013552:Swine
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D011108:Polymers; D002939:Ciprofloxacin
Ciprofloxacin; drug polymer interaction; mucoadhesion; ocular clearance; particle size