Fabrication and Characterization of Ocular Phase Transition Systems for Blepharitis: A Novel Approach

Author(s): Deepali Verma, Shreya Kaul, Neha Jain, Upendra Nagaich*

Journal Name: Drug Delivery Letters

Volume 10 , Issue 1 , 2020

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Graphical Abstract:


Abstract:

Introduction: In the present research, erythromycin estolate loaded in-situ gel was formulated and evaluated for blepharitis in order to improve its therapeutic efficacy, precorneal residence time of the system and to enhance the ocular bioavailability.

Materials and Methods: The developed formulation was characterized by several parameters viz. FTIR, clarity, pH, gelation temperature, rheological studies, drug content, in vitro drug release studies, transcorneal permeation studies, bioadhesion studies, isotonicity and stability studies.

Results: The optimized formulation exhibited non-fickian release diffusion with a sustained release of drug 82.76 ± 0.94% up to 8h and drug content 93.64%. Isotonicity revealed that the formulation was isotonic in nature and there was no shrinkage and busting of cells. Bioadhesion study was performed to check the adherence of the prepared in situ gel to the corneal surface for 4h. Ex vivo transcorneal permeation was observed to be significantly higher when compared with market eye drops. Histopathological studies were conducted to confirm the presence of normal ocular surface tissues by maintaining their morphological structures without causing damage to the tissues. The formulation was nonirritant as confirmed by the HET-CAM test. Stability studies and accelerated stability studies were conducted for 13 weeks and 26 weeks respectively and formulations were analyzed for the visual appearance, pH, viscosity, gelling capacity, drug content and in vitro drug release and results showed no change in the formulations.

Conclusion: The formulation was therapeutically efficacious, sterile, stable and provided controlled release over a period of time. The developed system could be a viable alternative to conventional eye drops for treatment of various ocular diseases.

Keywords: Ion activation, in situ gel, blepharitis, gellan gum, histopathological studies, HET-CAM test.

[1]
Kumar, D.; Jain, N.; Gulati, N.; Nagaich, U. Nanoparticles laden in situ gelling system for ocular drug targeting. J. Adv. Pharm. Technol. Res., 2013, 4(1), 9-17.
[http://dx.doi.org/10.4103/2231-4040.107495] [PMID: 23662277]
[2]
Gupta, H.; Jain, S.; Mathur, R.; Mishra, P.; Mishra, A.K.; Velpandian, T. Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system. Drug Deliv., 2007, 14(8), 507-515.
[http://dx.doi.org/10.1080/10717540701606426] [PMID: 18027180]
[3]
Khurana, A.K.; Ahluwalia, B.K.; Rajan, C.; Vohra, A.K. Acute psychosis associated with topical cyclopentolate hydrochloride. Am. J. Ophthalmol., 1988, 105(1), 91.
[http://dx.doi.org/10.1016/0002-9394(88)90128-6] [PMID: 3337198]
[4]
Swarbrick, J.; Boylan, J. Ocular drug formulation and delivery. Encyclopedia of Pharmaceutical Technology; Marcel Dekker: Ney York, 1995, pp. 43-75.
[5]
Felt, O.; Baeyens, V. ucosal drug delivery: Ocular. Encyclopedia of Controlled Drug Delivery; John Wiley and Sons , 1999. pp. (2)605-626.
[6]
Liu, Z.; Li, J.; Nie, S.; Liu, H.; Ding, P.; Pan, W. Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. Int. J. Pharm., 2006, 315(1-2), 12-17.
[http://dx.doi.org/10.1016/j.ijpharm.2006.01.029] [PMID: 16616442]
[7]
El-Kamel, A.H. In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. Int. J. Pharm., 2002, 241(1), 47-55.
[http://dx.doi.org/10.1016/S0378-5173(02)00234-X] [PMID: 12086720]
[8]
Mohanambal, E.; Arun, K.; Sathali, A. Formulation and evaluation of pH-triggered in-situ gelling system of levofloxacin. Ind. J. Pharm. Educ. Res., 2011, 45(1), 58-64.
[9]
Thygeson, P. Etiology and treatment of blepharitis; a study in military personnel. Arch. Ophthalmol., 1946, 36(4), 445-477.
[http://dx.doi.org/10.1001/archopht.1946.00890210453002] [PMID: 21002032]
[10]
Thygeson, P. Complications of staphylococcic blepharitis. Am. J. Ophthalmol., 1969, 68(3), 446-449.
[http://dx.doi.org/10.1016/0002-9394(69)90711-9] [PMID: 5807673]
[11]
Bartly, J. Mondino, MD; Andrew I. Caster, MD; Brent Dethlefs. A Rabbit Model of staphylococcal blepharitis. Arch. Ophthalmol., 1987, 105, 409-412.
[http://dx.doi.org/10.1001/archopht.1987.01060030129042]
[12]
Agnihotri, S.A.; Jawalkar, S.S.; Aminabhavi, T.M. Controlled release of cephalexin through gellan gum beads: effect of formulation parameters on entrapment efficiency, size, and drug release. Eur. J. Pharm. Biopharm., 2006, 63(3), 249-261.
[http://dx.doi.org/10.1016/j.ejpb.2005.12.008] [PMID: 16621483]
[13]
Shweta, K.; Ganesha, K.; Preeti, K. Development and in vitro characterization of ocular insert containing erythromycin. IRJP, 2012, 3(8), 246-250.
[14]
Sawarkar, P. Ravikumar and S. Pashte. In-situ ophthalmic gel forming solution of moxifloxacin hydrochloride for sustained ocular delivery. Int. J. Pharm. Sci. Res., 2016, 7(3), 1192-1205. [IJPSR].
[15]
Compatibilityand stability studies of erythromycin Estolate and Piperine mixture. J. Pharm. Res., 2011, 4(10), 3405-3408.
[16]
Vijaya, C.; Goud, K.S. Ion-activated in situ gelling ophthalmicdelivery systems of azithromycin. Indian J. Pharm. Sci., 2011, 73(6), 615-620.
[http://dx.doi.org/10.4103/0250-474X.100234] [PMID: 23112394]
[17]
Dholakia, M.; Thakkar, V.; Patel, N.; Gandhi, T. Development and characterisation of thermo reversible mucoadhesive moxifloxacin hydrochloride in situ ophthalmic gel. J. Pharm. Bioallied Sci., 2012, 4(Suppl. 1), S42-S45.
[http://dx.doi.org/10.4103/0975-7406.94138] [PMID: 23066202]
[18]
Jagdish balasubramaniam,Shri kant, Jayanta Kumar Pandit. In vitro and in vivo evaluation of the Gelrite® gellangum-based ocular delivery system for indomethacin. Acta Pharm., 2003, 53, 251-261.
[19]
Liu, Y.; Liu, J.; Zhang, X.; Zhang, R.; Huang, Y.; Wu, C. In situ gelling gelrite/alginate formulations as vehicles for ophthalmic drug delivery. AAPS PharmSciTech, 2010, 11(2), 610-620.
[http://dx.doi.org/10.1208/s12249-010-9413-0] [PMID: 20354916]
[20]
Patel, D.M.; Patel, D.K.; Patel, C.N. Formulation and evaluation of floating oral in situ gelling system of amoxicillin; International Scholarly Research Network Pharmaceutics, 2011, pp. 1-8.
[21]
Gupta, H.; Aqil, M.; Khar, R.K.; Ali, A.; Bhatnagar, A.; Mittal, G.; Jain, S. Development and characterization of 99mTc-timolol maleate for evaluating efficacy of in situ ocular drug delivery system. AAPS PharmSciTech, 2009, 10(2), 540-546.
[http://dx.doi.org/10.1208/s12249-009-9238-x] [PMID: 19424806]
[22]
Ankita Kapoor, G. D Gupta. In situ gel for treatment of bacterial conjunctivitis. Int. J. Pharm. Sci. Rev. Res., 2016, 40(2), 51-57.
[23]
Paulsson, M.; Hägerström, H.; Edsman, K. Rheological studies of the gelation of deacetylated gellan gum (Gelrite) in physiological conditions. Eur. J. Pharm. Sci., 1999, 9(1), 99-105.
[http://dx.doi.org/10.1016/S0928-0987(99)00051-2] [PMID: 10494003]
[24]
Higashiyama, M.; Inada, K.; Ohtori, A.; Tojo, K. Improvement of the ocular bioavailability of timolol by sorbic acid. Int. J. Pharm., 2004, 272(1-2), 91-98.
[http://dx.doi.org/10.1016/j.ijpharm.2003.11.035] [PMID: 15019072]
[25]
Velpandian, T.; Bankoti, R.; Humayun, S.; Ravi, A.K.; Kumari, S.S.; Biswas, N.R. Comparative evaluation of possible ocular photochemical toxicity of fluoroquinolones meant for ocular use in experimental models. Indian J. Exp. Biol., 2006, 44(5), 387-391.
[PMID: 16708892 ]
[26]
Mandal, S.; Thimmasetty, M.K.; Prabhushankar, G.; Geetha, M. Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int. J. Pharm. Investig., 2012, 2(2), 78-82.
[http://dx.doi.org/10.4103/2230-973X.100042] [PMID: 23119236]
[27]
Snehaprabha, lad.; Amrita, bajaj Thermosensitive in situ gel of brinzolamide for sustained ocular drug delivery ijprbs, 2015, 4(3), 378-397.
[28]
Balasubramaniam, J.; Kant, S.; Pandit, J.K. In vitro and in vivo evaluation of the Gelrite gellan gum-based ocular delivery system for indomethacin. Acta Pharm., 2003, 53(4), 251-261.
[PMID: 14769232]
[29]
Puranik, K.M. Tagalpallewar, AA Voriconazole In situ Gel for Ocular Drug Delivery. SOJ Pharm. Pharm. Sci., 2003, 2(2), 1-10.
[30]
Radhakrishnan, S.M. Fabrication of ophthalmic in situ gel of diclofenac potassium and its evaluation. Sch. Acad. J. Pharm., 2013, 2(2), 101-106.
[31]
M.M., Van Ooteghem Edman, P., Ed. Biopharmaceutics of Ocular Drug Delivery; CRC Press: Boca Raton , 1993. pp. 27-41.
[32]
Kotreka, U.K.; Davis, V.L.; Adeyeye, M.C. Development of topical ophthalmic In Situ gel-forming estradiol delivery system intended for the prevention of age-related cataracts. PLoS One, 2017, 12(2)e0172306
[http://dx.doi.org/10.1371/journal.pone.0172306] [PMID: 28222100]
[33]
Gratieri, T.; Gelfuso, G.M.; de Freitas, O.; Rocha, E.M.; Lopez, R.F. Enhancing and sustaining the topical ocular delivery of fluconazole using chitosan solution and poloxamer/chitosan in situ forming gel. Eur. J. Pharm. Biopharm., 2011, 79(2), 320-327.
[http://dx.doi.org/10.1016/j.ejpb.2011.05.006] [PMID: 21641994]
[34]
Spielmann, H. Ocular irritation. In vitro methods in pharmaceutical research; Castle, J.V; Gomez, M.J., Ed.; Academic: San Diego, 1997, pp. 265-287.
[http://dx.doi.org/10.1016/B978-012163390-5.50013-2]
[35]
Nagaich, U. Recent advances in ocular drug delivery system. J. Adv. Pharm. Technol. Res., 2014, 5(4), 151.
[http://dx.doi.org/10.4103/2231-4040.143022] [PMID: 25364691]
[36]
Srividya, B.; Cardoza, R.M.; Amin, P.D. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. J. Control. Release, 2001, 73(2-3), 205-211.
[http://dx.doi.org/10.1016/S0168-3659(01)00279-6] [PMID: 11516498]


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Article Details

VOLUME: 10
ISSUE: 1
Year: 2020
Page: [24 - 37]
Pages: 14
DOI: 10.2174/2210303109666190614115304
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