NOVEL IN SITU GELLING SYSTEMS IN OPHTALMIC PREPARATIONS

Concepción RENEDO* and José Ignacio PEREZ.Pharmacy Faculty. University of Seville.

conxitarela@yahoo.es

OB

JEC

TIV

ES

-Analysis of the different in situ gelling mechanisms

Study the excipients used in these formulations

-Publicize existing commercialpreparations

INTRODUCTION

Topical ophthalmic drug delivery is a challenge topharmaceutical industry: the unique anatomy and physiology of the eye make it difficult to reach an effective concentration of the drug at the target site.

New release systems are being developed with thefollowing objectives: increase corneal permeability and prolong the contact of the drug with the ocular surfaceto improve its bioavailability

In situ gelling systems: These are liquid formulationscontaining polymers in dispersion. Upon instillation in theeye, undergo sol-to-gel phase transition. Gelation is causedby variation in different stimuli such as pH, temperature orionic strength.

The mechanism of gelationoccurs by the formation ofbonds between negativelycharged polysaccharide chainsand mono and divalent tearcations (Ca+ 2, K+, Na+), forming athree-dimensional network .

The temperature at which the transition from sol to geloccurs is known as “gelation temperature” .When the temperature is higher than the GT, the hydrogenbonds are altered and as a consequence the hydrophobicinteractions increase, enabling the transition between the soland gel phases.

Thesepolymers undergoa transition intothe viscous gelphase at the pH ofthe tear fluid.

o Gellan gumo Sodium alginateo Chitosan

o Carbomerso Hydroxypropyl guar

o Methyl celluloseo Xyloglucano N-isopropylacrylamideo Poloxamer

MarketedPreparations

Timoptic XE®

o TimololMaleate

Gellan Gum

ArteOptic®

o CarteololHydrochloride

SodiumAlginate

BromSite®

o BromfenacSodium

Poloxamer407

Carbomers

Besivance®

o BesifloxacinHydrochloride

Poloxamer407

Carbomers

Systane®

Hydroxypropyl guar

Azasite ®

o Azithromycine

Poloxamer407

Carbomers

Cartens ®

o CarteololHydrochloride

SodiumAlginate

BIBLIOGRAPHY1) Abraham S, Furtado S, Bharath S, Basavaraj BV, Deveswaran R, Madhavan V. Sustained ophthalmic delivery of ofloxacin from an ion-activated in situ gelling system. Pak. J. Pharm. Sci. 2009; 22: 175–179. 2)Achouri D, Alhanout K, Piccerelle P, Andrieu V. Recent advances in ocular drug delivery. Drug Dev. Ind. Pharm. 2012; 39: 1599-1617. 3) Agrawal AK, Das M, Jain S. In situ gel systems as Smart carriers for sustained ocular drug delivery. Expert Opin. Drug Deliv. 2012; 9(4): 383-402. 4) Bhowmik M, Bain MK, Ghosh LK. Effect of salts on gelation and drug release profiles ofmethylcellulose-based ophthalmic thermo-reversible in situ gels. Pharm Dev Technol 2011; 16:1-7

RESULTS AND DISCUSSION

•- Easy, safe and reproducible administration

-- Simple and cheap technology: industry- oriented

-- Low marketing

- Increase in ocular bioavailability

-- Increased drug retention time

-- Less frequent administration: greater comfort for the patient

-- Xiloglucan as a potentialsubstitute for synthetic polymers

CONCLUSIONS

- Of all the preparationsmarketed, only two are in Spain: Arteoptic® and Systane®- There are three preparations in Phase 3 of clinical trials: DexaSite®, AzaSite Extra® and AzaSite Plus®

The in situ gelling systemsrepresent a revolution for thepharmaceutical industry becausethey combine the benefits ofliquid solutions and gels, benefiting the patient. Without a doubt, its field of research iswide and very promising