“Preparation and evaluation of azm-loaded nanocapsules intended for ophthalmic administration”.

DANIELA QUINTEROS; FERREIRA LUANA MOTA; SCHAFFAZICK SR; PALMA SANTIAGO; ALLEMANDI DANIEL

Rosario

Congreso; 2° Reunión Internacional de Ciencias Farmacéuticas. RICiFa 2012; 2012

RICiFa

PREPARATION AND EVALUATION OF AZM-LOADED NANOCAPSULES INTENDED FOR OPHTHALMIC ADMINISTRATION Quinteros DA*1, Ferreira LM*2, Schaffazick SR*2, Palma SD*1,Allemandi DA*1,Cruz L.*2 *1 Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. UNITEFA-CONICET-Ciudad Universitaria, X5000HUA-Córdoba, Argentina *2 Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, 97105-900, Santa Maria-RS, Brazil Introduction Acetazolamide (AZM) is a carbonic anhydrase inhibitor, mainly used to reduce intraocular pressure in the treatment or long-term management of glaucoma. However, the potential of topical treatment is limited, due to its low permeability in ocular epithelium. An alternative to overcome this limitation is the incorporation of AZM in nanoparticulate systems, such as polymeric nanocapsules (PNC). These systems are characterized by their small size, on the nanometric range, which improves the permeability through membranes. In this way, this work aimed to prepare and characterize AZM-loaded PNC using ethylcellulose (EC) and Eudragit® RS100 (EUD) as encapsulating polymers. Materials and Methods PNC loaded with AZM at 1.0, 1.5 and 2.0 mg/mL were prepared by interfacial deposition of EUD or EC using sorbitan monostearate and polysorbate 80 as surfactants and medium chain triglycerides as oily core. The formulations were characterized in terms of size and zeta potential (Zetasizer Nanoseries), pH (potentiometer), drug content (HPLC at 264 nm) and encapsulation efficiency (10,000 MW Amicon®). These parameters were checked during 60 days at room temperature and protected from light. In vitro release and transcorneal permeation studies were carried out in bicompartimental diffusion cells. Results Drug contents were close to their theoretical value and encapsulation efficiencies were high, indicating that all AZM is entrapped. pH values were around 5.0 for all samples. The formulations had particle sizes in the nanometric range (106-229 nm) and exhibited low polydispersion (0.99). n values indicated that the release was controlled by fickian diffusion. Permeation studies using cornea of rabbits showed that both formulations presented different behaviour. For PNC-EC the steady-state flux increased as drug concentration was raised, which is consistent with the result observed for the in vitro release profiles. On the other hand, the steady-state flux of PNC-EUD decreased with the increase of AZM concentration. Papp values indicated that PNC prepared at 1.0 mg/mL of AZM were the most efficient as drug permeation enhancer. Conclusion PNC seems to be a promising approach for ophthalmic administration of AZM. This novel formulation could be a promising alternative for a more efficient treatment of glaucoma. Acknowledgements: CONICET, UNC, UFSM. References (1) Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G. Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci 2002;16:53-61.