FORMULATION AND EVALUATION OF NIOSOMAL IN SITU GEL OF PREDNISOLONE SODIUM PHOSPHATE FOR OCULAR DRUG DELIVERY
Objective: The main purpose of the study was to develop niosomal in situ gel of prednisolone sodium phosphate (PSP) with increased bioavailability (enhanced permeation) and sustained action (drug retention at the target site).
Methods: Using different ratios of span 60 and cholesterol (chol), niosomes were prepared by thin film hydration method and optimized by evaluating different parameters like drug content, entrapment efficiency, particle size and in vitro drug diffusion study. The niosomal pellets were further incorporated in in situ gel, prepared by the cold method and further optimized by parameters like gelling parameters, mucoadhesive strength and in vitro, in vivo drug release study.
Results: The optimized niosomal formulation containing span 60 and chol in equal proportion (1:1) showed better drug content (DC) i.e. 86.3±0.39% and entrapment efficiency (EE) i.e. 83.4±0.22 with vesicle size of 465±0.24 nm. The in vitro drug diffusion study indicated t90 value of 490 min thus proving sustained action of the formulation. The optimized in situ gel containing poloxamer 407 (P407) and poloxamer 188 (P188) in the ratio of 1:2.7 showed gelation temperature at 37 ⁰C (physiological temperature of the body) and t90 value of 10 h thus depicting sustained action. The increased area under curve (AUC) value by 1.75 folds proved increased bioavailability of the drug.
Conclusion: Thus sustained drug delivery with increased bioavailability was designed for prednisolone sodium phosphate for the treatment of ocular inflammation.
2. Shell JW, Baker R. Diffusional systems for controlled release of drugs to the eye. Ann Ophthalmol 1974;6:1037–43, 1045.
3. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems-recent advances. Pro Retin Eye Res 1998;17:35–58.
4. Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm 2002;28:473–93.
5. Almeida H, Amaral MH, Lobao P, Sousa Lobo JM. Applications of poloxamers in ophthalmic pharmaceutical formulations: on overview. Expert Opin Drug Delivery 2013;10:1223–37.
6. Sasaki H, Yamamura K, Nishida K, Nakamura J, Ichikawa M. Delivery of drugs to the eye by topical application. Prog Ret Eye Res 1996;15:583–620.
7. Nirmal HB, Bakliwal SR, Pawar SP. In-situ gel: new trends in controlled and sustained drug delivery systems. Int J Pharm Tech Res 2010;2:1398–408.
8. Agarwal KI, Mehta N, Namdev A, Gupta AK. In-situ gel formation for ocular drug delivery systems: an overview. Asia J Bio Pharm 2010;1:1–7.
9. Champalal KD, Sushilkumar P. Current status of an ophthalmic in-situ forming hydrogel. Int J Pharm Bio Sci 2012;3:372–88.
10. Shell JW. Ophthalmic drug delivery systems. Surv Ophthalmol 1984;29:117–28.
11. Burstein NL, Anderson JA. Review: corneal penetration and ocular availability of drugs. J Ocul Pharmacol 1985;1:309–26.
12. Modi KA, Shelat PK. Applications of novel vesicular drug delivery system as ocular drug vehicles: a review. Int J Pharm Sci Res 2012;3:4554-61.
13. Sirbat D, Heussler LM, Hoffman M, Maincent P. Ways to improve ocular bioavailability for topical applications. J Fr Opthalmol 2000;23:505–9.
14. Kaur IP, Smitha R. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev Ind Pharm 2002;28:353–69.
15. Gupta A, Singh S, Kotla NG, Webster TJ. Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity. Int J Nanomed 2015;10:171-82.
16. Saettone MF, Chetoni P, Cerbai R, Mazzanti G, Braghiroli L. Evaluation of ocular permeation enhancers: in vitro effects on corneal transport of four betablockers, and in vitro/in vivo toxic activity. Int J Pharm 1996;142:103-13.
17. Carafa M, Santucci E, Alhaique F, Coviello T, Murtas E, Riccieri FM, et al. Preparation and properties of new unilamellar non-ionic surfactant vesicles. Int J Pharm 1996;160:51–9.
18. Aggarwal D, Garg A, Kaur IP. Development of a topical niosomal preparation of acetazolamide: preparation and evaluation. J Pharm Pharmacol 2004;56:1509–17.
19. Aggarwal D, Kaur IP. Improved pharmacodynamics of timolol maleate from a mucoadhesiveniosomal ophthalmic drug delivery system. Int J Pharm 2005;290:155–9.
20. Liaw J, Robinson JR. Ocular penetration enhancers. In: Mitra AK. editor. Ophthalmic drug delivery systems. Marcel Dekker: New York; 1993. p. 369–81.
21. Sasaki H, Igarashi Y, Nagano T, Yamamura K, Nishida K, Nakamura J. Penetration of beta-blockers in albino rabbits. J Pharm Pharmacol 2005;47:17–21.
22. Kaur IP, Smitha R. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev Ind Pharm 2002;28:353–69.
23. Tripathi KD. Essentials of medical Pharmacy. 5th ed. India: Jaypee Brothers Medical Publishers; 2004.
24. Aggarwal D, Garg A, Kaur IP. Development of a topical niosomal preparation, of acetazolamide: preparation and evaluation. J Pharm Pharmacol 2004;56:1509–17.
25. Chaudhari PD, Desai US. Synthesis and evaluation of water-insoluble but swellable polymer for ocular drug delivery. Indian J Pharm Educ Res 2019;53:23-33.
26. Mutha SS, Patel S, Bhopal AV. Thermo reversible niosomal gel as a potential ophthalmic drug delivery system for ganciclovir. Indo Am J Pharm 2013;3:9190-201.
27. Acharya A, Kiran Kumar GB, Ahmed MG, Paudel S. A novel approach to increase the bioavailability of candesartan cilexetil by proniosomal gel formulation: in vitro and in vivo evaluation. Int J Pharm Pharm Sci 2016;8:241-6.
28. Kumar BS, Krishna R, Lakshmi PS, Vasudev DT, Nair SC. Formulation and evaluation of niosomal suspension of cefixime. Asian J Pharma Clin Res 2017;10:194-201.
29. Mohawed O, El Ashmoony MM, Elgazayerly ON. Niosome-encapsulated clomipramine for transdermal controlled delivery. Int J Pharm Pharm Sci 2014;6:567-75.
30. Radha GV, Sastri KT, Prathyusha P, Bhanu P, Rajkumar J. Formulation and evaluation of aceclofenac proniosome loaded orabase for management of dental pain. Int J Appl Pharm 2018;10:204-10.
31. Asthana SG, Sharma PK, Asthana A. In vitro and in vivo evaluation of niosomal formulation for controlled delivery of clarithromycin. Scientifica 2016. Doi:10.1155/2016/ 6492953.
32. Zaki NM, Awad GA, Mortada ND, Abd Elhady SS. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci 2007;32:296–307.
33. Nikam PM, Gondkar SB, Saudagar RB. Formulation development and evaluation of pH-dependent brimonidine tartrate in-situ ophthalmic gel. World J Pharm Pharm Sci 2016;5:1682-703.
34. Hue HW, Robinson JR. Ocular delivery of progesterone using a bioadhesive polymer. Int J Pharm 1985;26:203-13.
35. Land Gel SS, Oswald RJ, Searle AS, Andre RV, Patel SY. Synthesis and evaluation of some novel theorems as mucoadhesive polymer. Der Parma Chemical 2012;4:1385-96.
36. Draize JH, Woodward G, Calvary HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucus membranes. J Pharmacol Ext Ther 1944;82:377-90.
37. Abraham MH, Kumar Singh, Cometto-Muniz, Cain WS. Draize eye scores and eye irritation thresholds in man combined into one quantitative structure-activity relationship. Toxicol In Vitro 1998;12:403-8.
38. Musson DG, Bidgood AM, Olejnik O. Comparative corneal penetration of prednisolone sodium phosphate and prednisolone acetate in NZW rabbits. J Ocul Pharmacol 1991;7:175-82.
39. Tayel AS, El-Nabarawi MA Tadros, Abd-Elsalam WH. Positively charged polymeric nanoparticle reservoirs of terbinafine hydrochloride: preclinical implications for controlled drug delivery in the aqueous humor of rabbits. AAPS PharmSciTech 2013;14:783-93.
40. ICH Harmonised tripartite guideline, stability testing of new drug substances and products Q1A (R2); 2003. p. 1-24.
41. Shatalebi MA, Mostafavi A, Moghaddas A. Niosome as a drug carrier for topical delivery of N-acetyl glucosamine. Res Pharm Sci 2010;5:107-17.
42. Abdelkader H, Adam WG, Alany G. Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug Delivery 2014;21:35-45.
43. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm 1998;172:33-70.
44. Kumar GP, Rajeshwarrao P. Nonionic surfactant vesicular systems for effective drug delivery an overview. Acta Pharma Sinica B 2011;1:208-19.
45. Panda N, Panda KC, Reddy AV, Subbareddy GV, Patro LR. Formulation design and in vitro evaluation studies of matrix diffusion controlled glipizide transdermal patch. J Phys Chem 2013;7:9-15.
46. DL Pavia, GM Lapman, GS Kriz. Inroduction to spectroscopy. third edition. Thomson learning Inc. 2001. p. 26.
47. Yadav K, Yadav D, Saroha K, Nanda S, Mathur P, Syan N. Proniosomal gel: a provesicular approach for transdermal drug delivery. Der Pharma Lett 2010;2:189–98.
48. Honary SE, Ebrahimi P, Tabbakhian M, Zahir F. Formulation and characterization of doxorubicin nanovesicles. J Vac Sci Technol B Microelectron Nanometer Struct 2009;27:1573–7.
49. Sezgin Bayindir Z, Yuksel N. Investigation of formulation variables and excipient interaction on the production of niosomes. AAPS PharmSciTech 2012;13:826–35.
50. Zhang Z, Feng SS. Self-assembled nanoparticles of poly (lactide)–vitamin E TPGS copolymers for oral chemotherapy. Int J Pharm 2006;324:191–8.
51. Liu S, Jones L, Gu FX. Nanomaterials for ocular drug delivery. Macromol Biosci 2012;12:608–20.
52. Ali Y, Lehmussaari K. Industrial perspective in ocular drug delivery. Adv Drug Delivery Rev 2006;57:1258–68.
53. Hamsika M, Gowda DV, Vindru J, Moin A. Nanotechnology for ophthalmic preparations. Int J Curr Pharm Res 2016;8:5-11.
54. Okore VC, Attama AA, Ofokansi KC, Esimone CO, Onuigbo EC. Formulation and evaluation of niosomes. Indian J Pharm Sci 2011;73:323–8.
55. Win KY, Feng SS. Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials 2005;26:2713–22.
56. Dumortier G, El Kateb N, Sahli M, Kedjar S, Boulliat A, Chaumeil JC. Development of a thermogelling ophthalmic formulation of cysteine. Drug Dev Ind Pharm 2006;32:63–72.
57. Yong CS, Choi JS, Quan Q, Jong-Dal R, Kim C, Lim S, et al. Effect of sodium chloride on the release, absorption, and safety of diclofenac sodium delivered by poloxamer gel. Int J Pharm 2001;263:195–205.
58. Baloglu E, Karavana SY, Zeynep AY, Guneri T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm Dev Technol 2010;16:627-36.
59. Badgujar SD, Sontakke MA, Narute DR, Karmarkar RR, Tupkar SV, Barhate SD. Formulation and evaluation of sumatriptan succinate nasal in situ gel using fulvic acid as a novel permeation enhancer. Int J Pharm Res Dev 2010;2:1–8.
60. Abdel Mottaleb MM, Mortada ND, Elshamy AA, Awad GA. Preparation and evaluation of fluconazolegels. Egypt J Biomed Sci 2007;23:266–86.
61. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems-recent advances. Prog Ret Eye Res 1998;17:33-58.
62. Dhiman M, Yedurkar P, Sawant KK. Formulation, characterization and in vitro evaluation of bioadhesive gels containing 5-Fluorouracil. Pharm Dev Tech 2008;13:15-25.
63. Abdelbary GA, Amin MA, Zakaria MY. Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies. Drug Delivery 2017;24:309-19.