NOVEL IN SITU GELLING SYSTEMS IN OPHTALMIC PREPARATIONS · 2018. 9. 25. · o Carteolol...
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NOVEL IN SITU GELLING SYSTEMS IN OPHTALMIC PREPARATIONS Concepción RENEDO* and José Ignacio PEREZ. Pharmacy Faculty. University of Seville. [email protected] OBJECTIVES -Analysis of the different in situ gelling mechanisms Study the excipients used in these formulations -Publicize existing commercial preparations INTRODUCTION Topical ophthalmic drug delivery is a challenge to pharmaceutical 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 the following objectives: increase corneal permeability and prolong the contact of the drug with the ocular surface to improve its bioavailability In situ gelling systems: These are liquid formulations containing polymers in dispersion. Upon instillation in the eye, undergo sol-to-gel phase transition. Gelation is caused by variation in different stimuli such as pH, temperature or ionic strength. The mechanism of gelation occurs by the formation of bonds between negatively charged polysaccharide chains and mono and divalent tear cations (Ca +2 ,K + , Na + ), forming a three-dimensional network . The temperature at which the transition from sol to gel occurs is known as “gelation temperature” . When the temperature is higher than the GT, the hydrogen bonds are altered and as a consequence the hydrophobic interactions increase, enabling the transition between the sol and gel phases. These polymers undergo a transition into the viscous gel phase at the pH of the tear fluid. o Gellan gum o Sodium alginate o Chitosan o Carbomers o Hydroxypropyl guar o Methyl cellulose o Xyloglucan o N-isopropylacrylamide o Poloxamer Marketed Preparations Timoptic XE® o Timolol Maleate Gellan Gum ArteOptic® o Carteolol Hydrochloride Sodium Alginate BromSite® o Bromfenac Sodium Poloxamer 407 Carbomers Besivance® o Besifloxacin Hydrochloride Poloxamer 407 Carbomers Systane® Hydroxy propyl guar Azasite ® o Azithromycine Poloxamer 407 Carbomers Cartens ® o Carteolol Hydrochloride Sodium Alginate BIBLIOGRAPHY 1) 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 of methylcellulose-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 potential substitute for synthetic polymers CONCLUSIONS - Of all the preparations marketed, 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 systems represent a revolution for the pharmaceutical industry because they combine the benefits of liquid solutions and gels, benefiting the patient. Without a doubt, its field of research is wide and very promising
Transcript of NOVEL IN SITU GELLING SYSTEMS IN OPHTALMIC PREPARATIONS · 2018. 9. 25. · o Carteolol...
NOVEL IN SITU GELLING SYSTEMS IN OPHTALMIC PREPARATIONS
Concepción RENEDO* and José Ignacio PEREZ.Pharmacy Faculty. University of Seville.
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
