Cubosomes; An Approach to Sustain and Improve the Ocular Delivery for Glaucoma Treatment: Box Benhken Optimization, Formulation, In Vitro Characterization and Ex Vivo Permeation Study

Shubhangi Aher; Bharati Nimase

doi:10.55544/jrasb.3.3.33

Authors

Dr. Shubhangi Aher Assistant Professor, Department of Pharmaceutics, Bombay College of Pharmacy, INDIA https://orcid.org/0000-0002-0993-5203
Bharati Nimase Masters, Department of Pharmaceutics, Bombay College of Pharmacy, INDIA

DOI:

https://doi.org/10.55544/jrasb.3.3.33

Keywords:

Acetazolamide, Glaucoma, Intraocular pressure, Cubosomes, Box-Behnken design, Transmission electron microscopy

Abstract

Introduction: In glaucoma, acetazolamide (ACZ) is used to lower intraocular pressure (IOP). Low aqueous solubility and decreased corneal permeation are two characteristics of ACZ. This research intends to enhance the ocular delivery of ACZ.

Materials and Methods: Using a Box-Behnken design, cubosomes loaded with acetazolamide were made using the Melt dispersion emulsification and sonication method. The independent variables included Glyceryl monoolein (GMO), polyvinyl alcohol (PVA) and Poloxamer 407 (P407. The prepared formulations underwent evaluation for polydispersity index (PDI), particle size and entrapment efficiency. Thermal analysis, in vitro characterisation and permeation were among the additional tests performed on the developed formulation.

Results: Optimized formulation showed PDI of 0.23 ± 0.03, mean particle size of 243 ± 4.2 nm, zeta potential of -26.1 ± 0.6 mV, entrapment efficiency of 73.99% and cubic structure under TEM. Drug penetration through goat cornea has increased, according to an ex vivo permeation study. The prepared cubosome safety, stability and ability to be delivered through the cornea were confirmed by the ocular irritation test.

Conclusion: The optimized cubosomal formulation has the potential to improve glaucoma treatment and be regarded as promising for ocular delivery of ACZ.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Jingfen Sun, Zhengshen Zhou. (2018). "A novel ocular delivery of brinzolamide based on gellan gum: in vitro and in vivo evaluation" , Drug Design, Development and Therapy.

J.B. Soltau, T. Zimmerman. (2002) Changing paradigms in the medical treatment of glaucoma, Surv. Ophthalmol. 47 S2–S5. doi: 10.1016/s0039-6257(02)00291-6

I.P. Kaur, H. Singh, S. Kakkar (2011) Newer therapeutic vistas for antiglaucoma medicines 28(2):165-202. doi: 10.1615/critrevtherdrugcarriersyst.v28.i2.20.

Wang, R.; Gao, Y.; Liu, A.; Zhai, G. (2021) A review of nanocarrier-mediated drug delivery systems for posterior segment eye disease: Challenges analysis and recent advances. J. Drug Target.1,1–31.

Parthibarajan R, Gowrishankar N, Prashanth D, Mallikarjun RV. (2011). Formulation and in-vitro evaluation of floating microspheres of acetazolamide. Int J Pharm Pharm Sci. 5(1):447–453.

Granero G, Maitre M, Garnero C, Longhi M. (2008). Synthesis, characterization and in vitro release studies of a new acetazolamide–HP-β-CD– TEA inclusion complex. Eur J Med Chem. 43(3):464–470. doi:10.1016/j.ejmech.2007.03.037.

Manchanda S, Sahoo P. (2017). Topical delivery of acetazolamide by encapsulating in mucoadhesive nanoparticles. Asian J Pharm Sci. 12 (6):550–557. doi:10.1016/j.ajps.2017.04.005.

Verma P, Ahuja M. (2016). Cubic liquid crystalline nanoparticles: optimization and evaluation for ocular delivery of tropicamide. Drug Deliv 23:3043–54.

Gan L, Wang J, Jiang M, et al. (2013). Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers. Drug Discov Today 18:290–7.

Chen Y, Ma P, Gui S. (2014). Cubic and hexagonal liquid crystals as drug delivery systems. Biomed Res Int 2014:815981–12.

Scriven LE. (1976). Equilibrium bicontinuous structure. Nature 263:123–5.

Esposito E, Cortesi R, Drechsler M, et al. (2005). Cubosome dispersions as delivery systems for percutaneous administration of indomethacin. Pharm Res 22:2163–73.

Huang J, Peng T, Li Y, et al. (2017). Ocular cubosome drug delivery system for timolol maleate: preparation, characterization, cytotoxicity, ex vivo, and in vivo evaluation. AAPS PharmSciTech 18:2919–26.

Elgindy N, Mehanna M, Mohyeldin S. (2016). Self-assembled nano-architecture liquid crystalline particles as a promising carrier for progesterone transdermal delivery. Int J Pharm 501:167–79. doi: 10.1016/j.ijpharm.2016.01.049.

Vaibhavi Srivastava, Vivek Singh, Dharmendra Kumar Khatri, Neelesh Kumar Mehra. (2023). "Recent trends and updates on ultradeformable and elastic vesicles in ocular drug delivery" , Drug Discovery Today.

M. Shokry, R.M. Hathout, S. Mansour. (2018). Exploring gelatin nanoparticles as novel nanocarriers for Timolol Maleate: augmented in-vivo efficacy and safe histological profile, Int. J. Pharm. 229–239. doi: 10.1016/j.ijpharm.2018.04.059.

El-Setouhy DA, Abdelmalak NS, Anis SE, Louis D. (2015). Leflunomide biodegradable microspheres intended for intra-articular administration: development, anti-inflammatory activity and histopathological studies. Int J Pharm 495:664–70. doi: 10.1016/j.ijpharm.2015.09.040.

Askarkar SS, Gupta KR (2016). Design and evaluation of ophthalmic delivery of bepotastine besilate from eye drop Pharm Methods. 7:104–1510. doi:5530/phm.2016.7.16.

Berthomieu, C.; Hienerwadel, R. (2009). Fourier transform infrared (FTIR) spectroscopy. Photosynth. R 101, 157–170. doi: 10.1007/s11120-009-9439-x.

Montenegro, L.; Castelli, F.; Sarpietro, M.G. (2018). Differential scanning calorimetry analyses of idebenone-loaded solid lipid nanoparticles interactions with a model of bio-membrane: A comparison with in vitro skin permeation data. Pharmaceuticals (Basel). 11(4):138. doi: 10.3390/ph11040138.

Malatesta, M. (2016). Transmission electron microscopy for nanomedicine: Novel applications for long-established techniques. Eur. J. Histochem. 60(4):2751. doi: 10.4081/ejh.2016.2751.

Yerikala R, Reddigari J, Kothapalli C.B. (2016). Evaluation for ocular delivery of tropicamide, Drug Deliv. 3043–305. Doi: https://doi.org/10.22270/jddt.v8i2.1765.

Nayakn, N.; Misra, M (2018) A review on recent drug delivery systems for posterior segment of the eye. Biomed Pharm. 107:1564–1582. doi: 10.1016/j.biopha.2018.08.138.

Abdullah T.A., Ibrahim N.J., Warsi M.H. (2016). Chondroitin sulfate chitosan nanoparticles for ocular delivery of bromfenac sodium: Improved permeation, retention, and penetration. Int J Pharm Invest. 6: 96-105. doi: 10.4103/2230-973X.177823.

N.M.Morsi, R. Nabil Shamma, N. Osama Eladawy, A.A. Abdelkhalek. (2019). Bioactive injectable triple acting thermosensitive hydrogel enriched with nano-hydroxyapatite for bone regeneration: in-vitro characterization, Saos-2 cell line cell viability and osteogenic markers evaluation, Drug Dev. Ind. Pharm. 45:787–804. https://doi.org/10.1080/03639045.2019.1572184.

Hundekar YR, Saboji J, Patil S, Nanjwade B. (2014). Preparation and evaluation of diclofenac sodium cubosomes for percutaneous administration. World J Pharm Sci 3:523–39.

Kulkarni CV, Wachter W, Iglesias-Salto G, et al. (2011). Monoolein: a magic lipid Phys Chem 13:3004–21.

Guidance for Industry Q1A (R2) Stability Testing of New Drug Substances and Products. (2003). U.S. Department of Health and Human Services. Food and Drug Administration. ICH:2–16

Abdelrahman FE, Elsayed I, Gad MK, et al. (2015). Investigating the cubosomal ability for transnasal brain targeting: in vitro optimization, ex vivo permeation and in vivo biodistribution. Int J Pharm 490:281–91. doi: 10.1016/j.ijpharm.2015.05.064.

A.A. Elbary, A.A. Aboelwafa, I.M. Al Sharabi. (2011). Once daily, high-dose mesalazine controlled-release tablet for colonic delivery: optimization of formulation variables using box–behnken design, AAPS PharmSciTech 12:1454–1464. https:// doi.org/10.1208/s12249-011-9708-9.

N.F. Younes, S.A. Abdel-Halim, A.I. Elassasy. (2018). Corneal targeted Sertaconazole nitrate loaded cubosomes: preparation, statistical optimization, in vitro characterization, ex vivo permeation and in vivo studies, Int. J. Pharm. 553:386–397, https://doi.org/10.1016/j.ijpharm.2018.10.057.

V.Teeranachaideekul, E.B. Souto, V.B. Junyaprasert, R.H. Müller. (2007). Cetyl palmitate based NLC for topical delivery of Coenzyme Q10–Development, physicochemical characterization and in vitro release studies, Eur. J. Pharm. Biopharm. 67:141–148, https://doi.org/10.1016/j.ejpb.2007.01.015.

Thomas, L.; Viswanad, V. (2012). Formulation and optimization of clotrimazole-loaded proniosomal gel using 32 factorial design. Sci. Pharm 80:731–748. https://doi.org/10.3797/scipharm.1201-03.

Ahmed S, Amin MM, Sayed S. (2023). Ocular Drug Delivery: a Comprehensive Review. AAPS PharmSciTech. 24(2):66. https://doi.org/10.1208/s12249-023-02516-9.

Hassan, D.H.; Abdelmonem, R.; Abdellatif, M.M. (2018). Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-vivo Pharmaceutics10:197. https://doi.org/10.3390/pharmaceutics10040197

J. Li, L. Wu, W. Wu, B. Wang, Z. Wang, H. Xin, Q. Xu, (2013). A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate, Int. J. Pharm. 455:75–84. https://doi.org/10.1016/j.ijpharm.2013.07.057.

Krsti´c, M.; Radojevi´c, M.; Stojanovi´c, D.; Radojevi´c, V.; Uskokovi´c, P.; Ibri´c, S. (2017). Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method. Eur. J. Pharm. Sci.101:160–166. https://doi.org/10.3390/pharmaceutics11020055.

Bunjes, H.; Unruh, T. (2007). Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv. Drug. Deliv. Rev. 59:379–402. https://doi.org/10.1016/j.addr.2007.04.013.

J. Sun, Y. Lei, Z. Dai, X. Liu, T. Huang, J. Wu, Z.P. Xu, X. Sun, (2017). Sustained release of brimonidine from a New composite drug delivery system for treatment of glaucoma, ACS Appl. Mater. Interfaces 9:7990–7999. https://doi.org/10.1021/acsami. 6b16509.

Zaki Randa., Khaled M. Hosny., Ahmed Khames., Ahmed Abdelbary. (2011). Ketorolac Tromethamine In-situ Ocular Hydro Gel; Preparation, Characterization, and In-vivo Evaluation. International Journal of Drug Delivery 3:535-545.

Anonymous. Indian Pharmacopoeia. Vol. 1-2. New Delhi (2007) The Controller of Publication, Govt. of India, Ministry of Health and Family Welfare. p. 52-9, 142-3, 565-8, 685-8.

De Araujo Lowndes Viera LM, Silva RS, da Silva CC. (2021). Comparison of the different protocols of the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) by evaluating the eye irritation potential of surfactants 78:105255. doi: 10.1016/j.tiv.2021.105255.

Nihal Farid Younes, Sally Adel Abdel-Halim, Abdelhalim I. Elassasy. (2018). "Corneal targeted Sertaconazole nitrate loaded cubosomes: Preparation, statistical optimization, in vitro characterization, ex vivo permeation and in vivo studies" , International Journal of Pharmaceutics.