Formulation and evaluation of dorzolamide hydrochloride-loaded nanoparticles as controlled release drug delivery system
Main Article Content
Abstract
Quasi-emulsion solvent diffusion technique. The formulations were evaluated in terms of particle size, zeta potential, drug entrapment, and release profile. All formulations showed tiny particle size varying from 114 to 395 nm for RS and
65 to 277 nm for RL. Positive zeta potential was +19 to +32 mV for RS and +23 to +42 mV for RL formulations. It was demonstrated that increasing polymer concentration lead to increase the percentage of drug entrapped in all batches, to
a certain extent (drug: polymer 1:4). Nanoparticles prepared using RL showed lower entrapment efficiency than RS. Incontrast, increasing the stirring rate resulted in an increase in the percentage of Dorzo entrapped. A prolonged drug release was shown by all the formulations. Increasing the polymer concentration caused a decrease in the release rate. Moreover, it was evident that increasing RL content increased the amount of Dorzo released. Dorzo-loaded nanoparticles could represent promising drug ophthalmic carriers, due to small particle size, positive zeta potential, and sustained release profile; hence, expecting prolonged corneal contact time, more therapeutically efficient, decreased frequency of administration per day,
and better patient compliance.
Downloads
Article Details
This is an Open Access article distributed under the terms of the Attribution-Noncommercial 4.0 International License [CC BY-NC 4.0], which requires that reusers give credit to the creator. It allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, for noncommercial purposes only.
References
Liu X, Rasmussen CA, Gabelt BT, Brandt CR, Kaufman PL. Gene therapy
targeting glaucoma: where are we? Surv Ophthalmol 2009;54:472-86.
Quigley HA, Broman AT. The number of people with glaucoma
worldwide in 2010 and 2020. Br J Ophthalmol 2006;90:262-7.
Maren TH.Carbonic anhydrase: General perspective and advances in
glaucoma research. Drug Dev Res 1987;10:255-76.
Sugrue MF. The preclinical pharmacology of dorzolamide hydrochloride,a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther
;12:363-76.
Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug
delivery. Drug Discov Today 2008;13:144-51.
Araújo J, Gonzalez E, Egea MA, Garcia ML, Souto EB. Nanomedicines for
ocular NSAIDS: safety on drug delivery. Nanomedicine 2009;5:394-40.
Nagarwal RC, Kant S, Singh PN, Maiti P, Pandit JK. Polymeric
nanoparticulate system: A potential approach for ocular drug delivery.
J Control Release 2009;136:2-13.
Das S, Suresh PK, Desmukh R. Design of Eudragit RL 100 nanoparticles
by nanoprecipitation method for ocular drug delivery. Nanomedicine
;6:318-23.
Dillen K, Weyenberg W, Vandervoort J, Ludwig A. The influence
of the use of viscosifying agents as dispersion media on the drug
release properties from PLGA nanoparticles. Eur J Pharm Biopharm
;58:539-49.
Gulsen D, Chauhan A. Ophthalmic drug delivery through contact lenses. Invest Ophthalmol Vis Sci 2004;7:2342-7.
Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK.
Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for
ocular delivery: Formulation, optimisation and in vitro characterisation.
Eur J Pharm Biopharm 2008;68:513-25.
Araújo J, Vega E, Lopes C, Egea MA, Garcia ML, Souto EB. Effect of
polymer viscosity on physicochemical properties and ocular tolerance
of FB-loaded PLGA nanospheres. Colloids Surf B Biointerfaces
;72:48- 56.
Röhm Pharma Publications, Data Sheet (Into RL/RS-4-e). Darmstadt:
Germany: Röhm GmbH;1990.
Bucolo C, Maltese A, Puglisi G, Pignatello R. Enhanced ocular anti-
inflammatory activity of ibuprofen carried by an Eudragit RS100
nanoparticle suspension. Ophthalmic Res 2002;34:319-23.
Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G. EudragitRS100 nanosuspensions for the ophthalmic controlled delivery of
ibuprofen. Eur J Pharm Sci 2002;16:53-61.
Castelli F, Messina C, Sarpietro MG, Pignatello R, Puglisi G. Flurbiprofen
release from Eudragit RS and RL aqueous nanosuspensions: A kinetic
study by DSC and dialysis experiments. AAPS PharmSciTech 2002;3:1-8.
Pignatello R, Bucolo C, Spedalieri G, Maltese A, Puglisi G. Flurbiprofen-
loaded acrylate polymer nanosuspensions for ophthalmic application.
Biomaterials 2002;23:3247-55.
Pignatello R, Ricupero N, Bucolo C, Maugeri F, Maltese A, Puglisi G.
Preparation and Characterization of Eudragit Retard Nanosuspensions
for the Ocular Delivery of Cloricromene. AAPS PharmSciTech
;7:E27.
Adibkia K, Siahi Shadbad MR, Nokhodchi A, Javadzedeh A,
Barzegar- Jalali M, Barar J, et al. Piroxicam nanoparticles for ocular
delivery: physicochemical characterization and implementation in
endotoxin-induced uveitis. J Drug Target 2007;15:407-16.
Adibkia K, Omidi Y, Siahi MR, Javadzadeh AR, Barzegar-Jalali M, Barar J,et al. Inhibition of endotoxin-induced uveitis by methylprednisolone
acetate nanosuspension in rabbits. J Ocul Pharmacol Ther
;23:421-32.
Das S, Suresh PK. Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to
amphotericin B. Nanomedicine 2011;7:242-7.
Pignatello R, Bucolo C, Puglisi G. Ocular tolerability of Eudragit RS 100
and RL 100 nanosuspensions as carriers for ophthalmic controlled drug
delivery. J Pharm Sci 2002;91:2636-41.
Kawashima Y, Niwa T, Handa T, Takeuchi H, Iwamoto T, Itoh K.
Preparation of controlled-release microspheres of ibuprofen with acrylic
polymers by a novel quasi-emulsion solvent diffusion method. J Pharm
Sci 1989;78:68-72.
Pignatello R, Vandelli MA, Giunchedi P, Puglisi G. Properties of Tolmetin-
loaded Eudragit RL100 and RS100 microparticles prepared by different
techniques. STP Pharma Sci 1997;7:148-57.
Kompella U, Bandi N, Ayalasomayajula S. Poly (lactic acid) nanoparticlesfor sustained release of budesonide. Drug Deliv Technol 2001;1:29-35.
Zimmer AK, Kreuter J. Microspheres and Nps used in ocular drug
delivery systems. Adv Drug Deliv Rev 1995;16:61-73.
Budhian A, Siegel SJ, Winey KI. Haloperidol-loaded PLGA nanoparticles:
systematic study of particle size and drug content. Int J Pharm
;336:367-75.
Nath B, Nath LK, Kumar P. Preparation and in vitro dissolution profile
of zidovudine loaded microspheres made of Eudragit RS 100, RL 100
and their combinations. Acta Pol Pharm 2011;68:409-15.
Kancharla K, Basavaraj BV, Bharath S, Deveswaran R, Madhavan V.
Formulation and evaluation of intragastric floating multiparticulate
system of Aceclofenac. Der Pharm Let 2011;3:238-45.
Benita S. Prevention of topical and ocular oxidative stress by positively
charged submicron emulsion. Biomed Pharmacother 1999;53:193-206.
Klang S, Abdulrazik M, Benita S. Influence of emulsion droplet surface
charge on indomethacin ocular tissue distribution. Pharm Dev Technol
;5:521-32.
Pignatello R, Amico D, Chiechio S, Spadaro C, Puglisi G, Giunchedi P.
Preparation and analgesic activity of Eudragit RS100 microparticles
containing diflunisal. Drug Deliv 2001;8:35-45.
Perumal D, Dangor CM, Alcock RS, Hurbans N, Moopanar KR. Effect
of formulation variables on in vitro drug release and micromeritic
properties of modified release ibuprofen microspheres. J Microencapsul
;16:475-87.
Pignatello R, Ferro M, De Guidi G, Salemi G, Vandelli MA, Guccione S,
et al. Preparation, characterisation and photosensitivity studies of solid
dispersions of diflunisal and Eudragit RS100 and RL100. Int J Pharm
;218:27-42.
Konan YN, Cerny R, Favet J, Berton M, Gurny R, Allemann E.
Preparation and characterization of sterile sub-200 nm meso-tetra
(4-hydroxylphenyl)porphyrine-loaded nanoparticles for photodynamic
therapy. Eur J Pharm Biopharm 2003;55:115-24.
Dandagi P, Kerur S, Mastiholimath V, Gadad A, Kulkarni A. Polymeric
ocular nanosuspension for controlled release of acyclovir: In vitro
release and ocular distribution. Iran J Pharm Res 2009;8:79-86.
Gaikwad A, Tamizhrasi S, Sorti A, Gavali P, Mehare G. Formulation and
in vitro characterization of polymethacrylic acid nanoparticle containing
Frusemide. Int J Pharm Tech Res 2010;2:300-4.
Bhosale UV, Devi VK. Preparation and In vitro Evaluation of acyclovir
loaded eudragit RLPO nanoparticles as sustained release carriers.
RGUHS J Pharm Sci 2011;1:85-92.
Khopade AJ, Jain NK. Self assembling nanostructures for sustained
ophthalmic drug delivery. Pharmazie 1995;50:812-4.
De Campos A, Sanchez A, Alonso M. Chitosan nanoparticles: a new
vehicle for the improvement of the delivery of drugs to the ocular
surface. Application to cyclosporin A. Int J Pharm 2001;224:159-68.
Romero-Cano M, Vinceent B. Controlled Release of 4-nitroanisole from
poly (lactic acid) nanoparticles. J Control Release 2002;82:127-35.
Bodmeier R, Chen H. Preparation and characterization of microspheres
containing the anti-inflammatory agents, Indomethacin, ibuprofen and
kitoprofen. J Control Release 1989;10:167-75.
Pignatello R, Consoli P, Pulgisi G. In vitro release kinetics of Tolmetin from
tabletted Eudragit microparticles. J Microencapsul 2000;17:373- 83.