Preparation and Characterization of Prednisolone Acetate Microemulsion for Ophthalmic Use

Reem Alfaris; Khalid  K Al-Kinani

doi:10.32007/jfacmedbagdad.2045

Authors

Reem Alfaris Collage of pharmacy/University of Baghdad https://orcid.org/0009-0005-8717-0970
Khalid K Al-Kinani Dept. Pharmaceutics College of Pharmacy Baghdad https://orcid.org/0000-0002-1233-8944

DOI:

https://doi.org/10.32007/jfacmedbagdad.2045

Keywords:

Keywords: Microemulsion, prednisolone acetate, oleic acid, particle size measurement, In vitro drug release, and Ex-vivo permeation study.

Abstract

Background: Prednisolone acetate is an ester form of prednisolone. It is used topically as an ophthalmic suspension to treat many inflammatory ocular conditions, where its absorption from suspension is highly variable and has poor dose accuracy.

Objectives: The main objective of this research is to formulate and evaluate prednisolone acetate microemulsion for ophthalmic use to increase solubility, residence time, and corneal permeability of the drug to enhance patient compliance and treatment efficacy.

Methods: Twenty-four prednisolone acetate-loaded microemulsion (0.5%w/w) formulas were prepared using oleic acid, isopropyl myristate as (oil phase) (1:1), tween 80, labrasol, and cremophor EL as (surfactant), ethanol, polyethylene glycol 400, propylene glycol, transcutol P as co-surfactant and Sörensen isotonic phosphate buffer saline pH 7.4 as the aqueous phase at different Smix ratios (1:1), (1:2) and (2:1) by aqueous titration method to construct pseudoternary phase diagram to determine the existence of microemulsion region. All the prepared formulas were subjected to different evaluation tests to determine the optimum formula.

Results: observations of the microemulsion showed that it had a clear and transparent yellowish color, formulation F9 composed of oleic acid and isopropyl myristate in a ratio (1:1) as oil, twee80 as a surfactant, and propylene glycol: ethanol (1:1) in a ratio (2:1) as cosurfactant gave the best particle size (10.18nm), polydispersity index (0.2216), zeta potential (-25,91), % of transmittance (99.382%±0. 09), and drug content (100±0.16). Microemulsion formulation provided considerably higher permeability than the marketed eye drop suspension (Optipred®) and improved bioavailability.

Conclusions: The microemulsion-containing prednisolone acetate is a promising ocular carrier for the controlled release of prednisolone acetate in treating anterior segment inflammation.

Received: Dec. 2022

Accepted March 2023

Published: Oct.2023

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References

Stjernschantz J, Astin M. Anatomy and physiology of the eye. Physiological aspects of ocular drug therapy. In: Biopharmaceutics of ocular drug delivery. CRC Press; 2019. p. 1–25. https://doi.org/10.1201/9780429284755-1

Qi J, He W, Meng J, Wei L, Qian D, Lu Y, et al. Distribution of Ocular Anterior and Posterior Segment Lengths Among a Cataract Surgical Population in Shanghai. Front Med (Lausanne). 2021;1653.

https://doi.org/10.3389/fmed.2021.688805.

Castro BFM, de Oliveira Fulgêncio G, Domingos LC, Cotta OAL, Silva-Cunha A, Fialho SL. Positively charged polymeric nanoparticles improve ocular penetration of tacrolimus after topical administration. J Drug Deliv Sci Technol. 2020; 60:101912. https://doi.org/10.1016/j.jddst.2020.101912 .

Ch Ismael M, Ibrahim AH, Kadim RL, Mubarak EA. Study of causative bacterial agents and risk factors predisposing to bacterial keratitis in Iraq. Vol. 59, J Fac Med Baghdad Fac Med Baghdad. 2017.

https://doi.org/10.32007/jfacmedbagdad.591173.

Jumelle C, Gholizadeh S, Annabi N, Dana R. Advances and limitations of drug delivery systems formulated as eye drops. Journal of Controlled Release. 2020; 321:1–22. https://doi.org/10.1016/j.jconrel.2020.01.057.

Sadeq ZA, Sabri LA, Al-Kinani KK. Natural polymer Effect on gelation and rheology of ketotifen-loaded pH-sensitive in situ ocular gel (Carbapol). Journal of Advanced Pharmacy Education and Research. 2022;12(2):45–50. https://doi.org/10.51847/zof4tcfekt.

Hegde RR, Verma A, Ghosh A. Microemulsion: new insights into the ocular drug delivery. Int Sch Res Notices. 2013;2013. https://doi.org/10.1155/2013/826798.

Popa L, Ghica MV, Dinu-Pîrvu CE, Irimia T. Chitosan: A good candidate for sustained release ocular drug delivery systems. Chitin-Chitosan—Myriad Functionalities in Science and Technology; InTech: London, UK. 2018;283–310. https://doi.org/10.5772/intechopen.76039/

Bodkhe AA, Bedi RS, Upadhayay A, Kale MK. Ophthalmic Microemulsion: Formulation Design and Process Optimization. Res J Pharm Technol. 2018;11(12):5474–82. https://doi.org/10.5958/0974-360x.2018.00998.8.

Mazet R, Yaméogo JBG, Wouessidjewe` D, Choisnard L, Gèze A. Recent advances in the design of topical ophthalmic delivery systems in the treatment of ocular surface inflammation and their biopharmaceutical evaluation. Pharmaceutics. 2020;12(6):570. https://doi.org/10.3390/pharmaceutics12060570.

Joshi H, Shelat P, Dave D. Optimization and characterization of lipid based nanoemulsion of prednisolone acetate for ophthalmic drug delivery. Research Journal Pharmacy and Technology. 2020;13(9):4139–47.

https://doi.org/10.5958/0974-360x.2020.00731.3.

Gopi J, Sharma UK. Bioadhesive Inserts of Prednisolone Acetate for Postoperative Management of Cataract–Development, and Evaluation. International Journal of Innovative Science and Research Technology ISSN No: -2456-2165. 2019;4(8).

Delgado JN. Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry. Beale B and, editor. Lippincott; 2011. 25:858.

Ibrahim MM, Maria DN, Wang X, Simpson RN, Hollingsworth TJ, Jablonski MM. Enhanced corneal penetration of a poorly permeable drug using bioadhesive multiple microemulsion technology. Pharmaceutics. 2020;12(8):704. https://doi.org/10.3390/pharmaceutics12080704.

KURJI AS, GAWHAR A. Characterization and formulation of prednisolone acetate reconstituted suspension. J Pharm Res. 2017;11(7):815–22.

Cheng YH, Chang YF, Ko YC, Liu CJ ling. Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study. Int J Biol Macromol. 2021; 180:365–74.

https://doi.org/10.1016/j.ijbiomac.2021.03.017.

Kumar R, Sinha VR. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf B Biointerfaces. 2014; 117:82–8. https://doi.org/10.1016/j.colsurfb.2014.02.007.

Salman AH, Al-Gawhari FJ, Al-kinani KK. The effect of formulation and process variables on prepared etoricoxib Nanosponges. Journal of Advanced Pharmacy Education 2021;11(2):82–7. and Research.

https://doi.org/10.51847/q0qrkuv2kq.

Berkman MS, Gulec K. Pseudo ternary phase diagrams: a practical approach for the area and centroid calculation of stable microemulsion regions. Journal of the Faculty of Pharmacy of Istanbul University. 2021;51(1):42–50. https://doi.org/10.26650/istanbuljpharm.2020.0090.

Lallemand F, Daull P, Benita S, Buggage R, Garrigue JS. Successfully improving ocular drug delivery using the cationic nanoemulsion, novasorb. J Drug Deliv. 2012;2012. https://doi.org/10.1155/2012/604204.

Taher SS, Al-Kinani KK, Hammoudi ZM, mohammed Ghareeb M. Co-surfactant effect of polyethylene glycol 400 on microemulsion using BCS class II model drug. Journal of Advanced Pharmacy Education & Research| Jan–Mar. 2022;12(1). https://doi.org/10.51847/1h17tzqgyi.

Dahash RA, Rajab NA. Formulation and Investigation of Lacidipine as a Nanoemulsions. Iraqi J. Pharma. Sc. 2020;29(1):41–54. https://doi.org/10.31351/vol29iss1pp41-54.

Ghareeb MM. Formulation and characterization of isradipine as oral nanoemulsion. Iraqi J Pharma. Sci. 2020;29(1):143–53. https://doi.org/10.31351/vol29iss1pp143-153.

Hussein AA. Preparation and evaluation of liquid and solid self-microemulsifying drug delivery system of mebendazole. Iraqi J. Pharma.Sc.2014;23(1):89-100.https://doi.org/10.31351/vol23iss1pp89-100.

Al-mahallawi AM, Ahmed D, Hassan M, El-Setouhy DA. Enhanced ocular delivery of clotrimazole via loading into mucoadhesive microemulsion system: In vitro characterization and in vivo assessment. J Drug Deliv Sci Technol. 2021 Aug 1; 64:102561. https://doi.org/10.1016/j.jddst.2021.102561.

International Pharmacopeia-Ninth Edition (USP44-NF39). monograph of prednisolone acetate. Ninth. Vol. 3. 2021. 3063 p.

Leone G, Pepi S, Consumi M, Mahdizadeh FF, Lamponi S, Magnani A. Phosphorylated xanthan gum-Ag (I) complex as antibacterial viscosity enhancer for eye drops formulation. Carbohydr Polym. 2021; 267:118196.

https://doi.org/10.1016/j.carbpol.2021.118196.

Phan CM, Shukla M, Walther H, Heynen M, Suh D, Jones L. Development of an in vitro blink model for ophthalmic drug delivery. Pharmaceutics. 2021;13(3):300. https://doi.org/10.3390/pharmaceutics13030300,

Ho TM, Abik F, Mikkonen KS. An overview of nanoemulsion characterization via atomic force microscopy. Vol. 62, Critical Reviews in Food Science and Nutrition. Taylor and Francis Ltd.; 2022. p. 4908–28.

https://doi.org/10.1080/10408398.2021.1879727.

Elfiyani R, Amalia A, Pratama SY. Effect of using the combination of tween 80 and ethanol on the forming and physical stability of microemulsion of eucalyptus oil as antibacterial. Journal of Young Pharmacists. 2017 Jan 1;9(1):S1–4. https://doi.org/10.5530/jyp.2017.1s.1.

Bali V AMAJ. Study of surfactant combinations and development of a novel nanoemulsion for minimizing variations in bioavailability of ezetimibe. Colloids Surfaces B Biointerfaces. 2010;76(2):410–20.

https://doi.org/10.1016/j.colsurfb.2009.11.021.

Sarheed O, Dibi M, Ramesh KV. Studies on the effect of oil and surfactant on the formation of alginate-based O/W lidocaine nanocarriers using nanoemulsion template. Pharmaceutics. 2020; 12(12):1223.

https://doi.org/10.3390/pharmaceutics12121223.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Vol. 10, Pharmaceutics. MDPI AG; 2018. https://doi.org/10.3390/pharmaceutics10020057

Hanaa M, Saleh AS, Shaimaa E. Design and optimization of self-nanoemulsifying drug delivery systems of simvastatin aiming dissolution enhancement. Afr J Pharm Pharmacol. 2013;7(22):1482–500.

https://doi.org/10.5897/ajpp2013.2987.

Al-Tamimi DJ, Hussein AA. Formulation and characterization of self-microemulsifying drug delivery system of tacrolimus. Iraqi J Pharma. Sci. 2021 Jun 15; 30(1):91-100. https://doi.org/10.31351/vol30iss1pp91-100.

Gawin-Mikołajewicz A, Nartowski KP, Dyba AJ, Gołkowska AM, Malec K, Karolewicz B. Ophthalmic nanoemulsions: from composition to technological processes and quality control.

https://doi.org/10.1021/acs.molpharmaceut.1c00650

de Villiers M. Buffers and pH Adjusting Agents.A Practical Guide to Contemporary Pharmacy Practice and Compounding. Vol. 4. 2009. 223–9 p