MUCOADHESIVE POLYMERIC FILMS OF ACYCLOVIR PRONIOSOMES FOR BUCCAL ADMINISTRATION
Objective: The aim of the present work was to formulate and evaluate proniosomes of poorly soluble drug, acyclovir incorporated in mucoadhesive polymeric films for improved buccal mucosal permeability of the drug while achieving prolonged release. Methods: Acyclovir was formulated as proniosomes using Span 60 and cholesterol. The prepared proniosomes were loaded into mucoadhesive polymeric films prepared with varying quantities of carbopol 934P and HPMC K15M. The proniosome incorporated films were evaluated for physico-mechanical characters, mucoadhesion, swelling index, drug content, in vitro drug release and ex vivo permeation through porcine buccal mucosa. Results: Hydration of the proniosomes produced spherical vesicles or niosomes which was confirmed by Scanning Electron Microscopy. The optimized formulation selected on the basis of vesicle size, entrapment efficiency PDI, Zetz potential and in vitro drug release was selected for incorporation into mucoadhesive polymeric films. All the films showed excellent physico-mechanical characters. Formulations with higher proportions of carbopol produced slower in vitro drug release. The kinetics of release of drug from all the formulations appeared to be zero order based on their regression coefficient values. Comparative evaluation of ex vivo permeation from niosomal and non niosomal films indicated that the former demonstrated improved mucosal permeation and drug release was also sustained for the 8 h period. Conclusion: Mucoadhesive films impregnated with acyclovir loaded proniosomes could be a potential approach for buccal delivery of acyclovir for improving its absorption and bioavailability.
2. Drug Bank, 2012, http://www.drugbank.ca/drugs/DB00787
3. Johnson GL, Limon L, Trikha G, Wall H. Acute renal failure and neurotoxicity following oral acyclovir. Ann Pharmacother 1994; 28:460-3
4. Cortesi R, Esposito E. Acyclovir delivery systems. Expert Opin Drug Deliv 2008; 5:1217–30.
5. Paul S, Kumar A, Yedurkar P, Sawant K. Design and development of multiple emulsion for enhancement of oral bioavailability of acyclovir. Drug Dev Ind Pharm 2013;39:1809–17
6. Swarbrick J, Boylan JC, editors. Buccal Absorption of Drugs. Encyclopedia of Pharmaceutical Technology, Vol.2. New York: Marcel Dekker Inc.; 1990. p.189-208
7. Jian-Hwa G, Karsten C. Development of Bioadhesive Buccal Patches. In: Swarbrick J, Mathiowitz E, editors. Bioadhesive Drug Delivery Systems: Fundamentals, Novel Approaches and Development. 1st ed. New York: Marcel Dekker Inc.; 1999. p. 541-59
8. Rossi S, Sandri G, Ferrari F, Bonferoni M, Caramella C. Buccal Delivery of Acyclovir from Films Based on Chitosan and Polyacrylic Acid. Pharm Dev Technol 2003;8:199-208.
9. De?im T, E?len B, Ocak Ö. A sustained release dosage form of acyclovir for buccal application: An experimental study in dogs. J Drug Target 2006;14(1):35-44.
10. Mahale N, Thakkar P, Mali R, Walunj D, Chaudhari S. Niosomes: Novel sustained release nonionic stable vesicular systems — An overview. Adv Colloid Interface Sci 2012;183-184:46-54.
11. Chaw CS, Ah Kim KY. Effect of formulation compositions on niosomal preparations. Pharm Dev Technol 2013; 18:667–72
12. Yadav K, Yadav D, Mathur P, Syan N. Pronisomal gel: a provesicular appraoch for transdermal drug delivery. Der Pharmacia Lettre. 2010;2(4):189-98
13. Mokhtar, M.; Sammour, O.A.; Hammad, M.A.; Megrab, N.A. Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm 2008; 361, 104–11
14. Mokale VJ, Ajit P, Priyanka P, Harshada I. Formulation and optimization of famotidine proniosomes: an in vitro and ex vivo study. J Expt Nano Sci 2016;11(2):54-65
15. Viviane F, Safaa S, Allam AN. Proniosomes as a Stable Carrier for Oral Acyclovir: Formulation and Physicochemical Characterization. J American Sci 2012;8(9):417-427.
16. Benipal G. Design, Development and Evaluation of Proniosomal Gel of an Antifungal Drug – Ketoconazole. Int J Pharm Sci Rev Res 2015;31(2):265-272
17. Ram A, Thakur A, Mittal V. Pronisomal provesicular system for transdermal delivery of hydralazine for hypertension. Asian J Pharm Clin Res. 2012;5(3):219-225.
18. Sathali AAH, Rajalakshmi G. Evaluation of transdermal targeted niosomal drug delivery of terbinafine hydrochloride. Int J PharmTech Res 2010;2(3):2081–89
19. Lohani A, Prasad N, Arya K. Formulation and characterization of mucoadhesive buccal films of ranitidine hydrochloride. Int J Pharma Sci Res. 2011;2(9):2457-2462
20. Satish Babu BK, Srinivasan BP. Preparation and evaluation of buccoadhesive films of Atenolol. Ind J Pharm Sci, 2008; 175-179. 19.
21. Koland M, Sandeep VP, Charyulu NR. Fast dissolving sublingual films of ondensetron hydrochloride effect of additives on in-vitro drug release and mucosal permeation. J Young Pharm 2010; 2 (3): 216-222.
22. Khanna R, Agrawal SP, Ahuja A. Preparation and evaluation of buccal films of clotrimazole for oral candida infections. Indian J Pharm Sci 1997; 59: 299-305.
23. Sang-Chul Shin, Ja-Young Kim. Enhanced permeation of triamcinolone acetonide through the buccal mucosa. Eur J Pharm Biopharm 2000; 50(2): 217-20
24. Lohani A, Prasad N, Arya K. Formulation and characterization of mucoadhesive buccal films of ranitidine hydrochloride. Int J Pharm Sci Res 2011;2(9):2457-2462.
25. Mane PP, Bushetti SS, Keshavanti GG. Development and in vitro evaluation of mucoadhesive buccal films of nebivolol. Indian J Pharm Sci 2014;76(2):166-169.
26. Lodhi M, Dubey A, Narayan R, Priya S. Formualtion and evaluation of buccal film of Ivabradine hydrochloride for the treatment of stable angina pectoris. Int J Pharm Investig 2013;3(1):47-53.
27. Nafee NA, Boraie NA, Ismail FA, Mortada LM. Design and characterization of mucoadhesive buccal patches containing Cetylpyridinium chloride. Acta Pharm 2003; 53:199-212
28. Fernandes F, Fortes A, da Cruz Fonseca S, Breitkreutz J, Ferraz H. Manufacture and Characterization of Mucoadhesive Buccal Films Based on Pectin and Gellan Gum Containing Triamcinolone Acetonide. Int J Polym Sci 2018;2018:1-10.
29. Balakrishnana P., Shanmugama S., Leea W. S., Leea W. M., Kim J. O. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int J Pharm 2009;377(1-2):1–8
30. Rogerson A, Cummings J, Florence AT. Adriamycin-loaded niosomes: drug entrapment, stability and release. J Microencapsul 1987;4:321–328
31. Peh KK, Wong CF. Polymeric fims as vehicles for buccal delivery: Swelling, Mechanical and Bioadhesive properties. J Pharm Pharmaceut Sci 1999; 2(2): 53-61
32. Anlar S, Capan Y, Hincal AA. Physico-chemical and bioadhesive properties of polyacrylic acid polymers. Pharmazie. 1993;48(4):285–7
33. Sharmin N, Al-Mamun MD, Jalil R. A novel method to study the effect of pH and excipients on water uptake and swelling behaviour of Carbopol polymers. Bangl Pharm J. 2010;3(2):1–7
34. Patel, M.M.; Smart, J.D.; Nevell, T.G.; Ewen, R.J.; Eaton, P.J.; Tsibouklis, J. Mucin/poly(acrylic acid) interactions: A spectroscopic investigation of mucoadhesion. Biomacromolecules 2003, 4, 1184–90
35. Peppas NA, Analysis of Fickian and non Fickian drug release from polymers, Pharm. Acta Helv. 60(1985) 110–1
36. Shah JC. Analysis of permeation data: evaluation of lag time method. Int J Pharm 1993;90:161–169
This work is licensed under a Creative Commons Attribution 4.0 International License.