Acetazolamide corneal permeation from interpolyelectrolite-drug complexes

PALENA, MC.; TÁRTARA, I.; QUINTEROS, D.; PALMA, SD.; ALLEMANDI, DA.; MANZO, RH.; JIMENEZ KAIRUZ, AF.

Rosario

Congreso; 41 Simposio Anual de la SAFE; 2009

SAFE

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; mso-layout-grid-align:none; punctuation-wrap:simple; text-autospace:none; font-size:10.0pt; font-family:"Arial","sans-serif"; mso-fareast-font-family:"Times New Roman";} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt;} @page WordSection1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.WordSection1 {page:WordSection1;} --> Acetazolamide (ACZ) is an inhibitor of carbonic anhydrase used mainly in the management of glaucoma by oral route. Due to its low solubility and poor corneal permeability there is no ocular formulation available. In this work we present    interpolyelectrolyte/drug complexes (DIPEC) using two opposite charged polyelectrolytes, Eudragit E100 (EE) and Eudragit L100 (EL) as ACZ potential carriers. Different EE:EL stoichiometric composition in aqueous dispersion were prepared:  EE:ACZ:EL (1:0,07:x ), where x= 0 to 0,5. The influence of EE:EL ratio on turbidity, particle size, electrokinetic  potential (z) and in vitro release characteristics of the particles were investigated. In vitro release using Franz cells with synthetic membranes, phosphate buffer (pH 7,4) and simulated lachrymal fluid as receptor media were performed. Additionally, permeability assay through rabbit cornea using ringer solution as receptor media was carried out. As the proportion of EL increased an increment in relative turbidity and a smooth decrease of z were observed. Particle size was dependent on EE:EL ratio, varying between 50 and 1500 nm.. These facts could be related to nanoparticles formation. ACZ release rate decreased from 32 to 18 µg.sec-0,5.cm-2 with the increase of EL proportion and release profiles did not show any difference between both receptor media. Corneal permeability of ACZ from EE:ACZ:EL (1:0,07:0,05) was studied and yielded five folds higher than that from ACZ solution. DIPEC could be considered as an interesting ACZ carrier to improve glaucoma treatment by ocular controlled delivery.  Additionally in vivo studies should be performed in order to evaluate efficacy and pharmacokinetic.