Design and characterization of Timolol maleate and Travoprost hydrogel drug delivery system

Main Article Content

Umadevi S
Musharaf M
Josephine Leno Jenita J

Keywords

Cross‑linking, differential scanning calorimetry, fourier transform infrared spectroscopy, glaucoma,hydrogels,scanning electron microscopy, X‑ray diffraction

Abstract

Hydrogels are comprised of a cross-linked network of polymers. Water penetrates these networks, resulting in swelling and giving the hydrogel a soft and rubbery consistency, thereby maintaining the integrity of the membrane. Because of the drawback of conventional therapy for ocular delivery, a hydrogel membrane containing a combination of timolol maleate and Travoprost were formulated for the treatment of glaucoma. In the present investigation, hydrogel membranes were prepared using polymers like gelatin, PVA and chitosan, which were cross‑ linked using physical and/or chemical methods. The cross‑linking of the membranes was confirmed by Fourier transform infrared spectroscopy (FTIR), X‑ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies. From the scanning electron microscopy (SEM) of the membranes, it appeared homogenous and showed no separation. The pH of the membranes ranged from 7.21‑7.4. The hydrogels showed a considerably good swelling ratio ranging from 91.66‑372.72%. The drug content ranged from 82.78‑95.62%. The in vitro drug release study indicated that there was a slow and sustained release of the drug from the membranes that were sufficiently cross‑linked and followed zero order release. The Intraocular pressure (IOP) lowering activity of the prepared formulation was compared with the marketed formulation, and it was found that the IOP lowering action was sustained for a long period of time. Stability studies proved that the formulations could be stable when stored at room temperature. Results of the study indicate that it is possible to develop a safe and physiologically effective hydrogel that is patient compliant.

Abstract 130 | pdf Downloads 152

References

1. Anumolu SS, Singh Y, Gao D, Stein S, Sinko PJ. Design and evaluation of novel fast forming pilocarpine-loadedocular hydrogels for sustained pharmacological response. J Control Release 2009;137:152-9.
2. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R.Ophthalmic drug delivery systems-recent advances. Prog Retin Eye Res 1998;17:33-58.
3. Gupta SK, Niranjan DG, Agrawal SS, Srivastava S, Saxena R. Recent advances in Pharmacotherapy of glaucoma. Indian J Pharmacol 2008;40:197-208.
4. Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer 2008;49:1993-2007.
5. Shastri DH, Patel LD. A novel alternative to ocular drug delivery system: Hydrogel. Int JPharm Res 2010;2:1-13.
6. Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J. Physicochemical foundations andstructural design of hydrogels in medicine and biology. Annu Rev Biomed Eng 2000;2:9-29.
7. Nanjawade BK, Manvi FV, Manjappa AS. In situ-forming hydrogels for sustained ophthalmicdrug delivery. J Control Release 2007;122:119-34.
8. Pal K, Banthia AK, Majumdar DK. Preparation and characterization of polyvinyl alcohol gelatin hydrogel membranes for biomedical applications. AAPS Pharm Sci Tech 2007;8:21.
9. Bolto B, Tran T, Hoang M, Xie Z. Crosslinked poly (vinyl alcohol) membranes. Prog Polym Sci 2009;34:969-81.
10. Mangala E, Kumar TS, Baskar S, Rao KP. Development of chitosan/ poly (vinylalcohol) blends membranes as burn dressings. Trends Biomater Artif Organs 2003;17:34-40.
11. Patel UL, Chotai NP, Nagda CD, Patel KN, Patel MP. Preparation and evaluation of ocular inserts for controlled delivery of gatifloxacin sesquihydrate. Int J Pharm Sci 2009;1:343-52.
12. Zhao L, Mitomo H, Zhai M, Yoshii F, Nagasawan N, Kume T. Synthesis of antibacterial PVA/CM-Chitosan blend hydrogels with electron beam irradiation. Carbohydr Polym 2003;53:439-46.
13. Yang JM, Su WY, Leu TL, Yang MC. Evaluation of chitosan/PVA blended hydrogel membranes. J Memb Sci 2004;236:39-51.
14. Bhanja S, Ellaiah P, Martha SK, Sahu PK, Tiwari SP, Panigrahi BB, et al. Formulation and in vitro evaluation of mucoadhesive buccal tablets of Timolol maleate. Int J Pharm Biomed Res 2010;1:129-34.
15. Mishra DN, Gilhotra RM. Design and characterization of bioadhesive in‑situ gelling ocular inserts of gatifloxacin sesquihydrate. DARU 2008;16:1-8.
16. Chetoni P, Di Colo G, Grandi M, Morelli M, Saettone MF, Darougar S. Siliconerubber/hydrogel composite ophthalmic inserts: Preparation and preliminary in vitro/in vivo evaluation. Eur J Pharm Biopharm 1998;46:125-32.
17. Mundada AS, Shrikhande BK. Controlled release gel of ciprofloxacin HCl for ophthalmic administration. Indian Drugs 2006;43:9-12.
18. Liu Z, Li J, Nie S, Liu H, Ding P, Pan W. Study of analginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. Int J Pharm 2006;315:12-7.
19. Aggarwal D, Garg A, Kaur IP. Development of a topical niosomal preparation of acetazolamide: Preparation and evaluation. JPharm Pharmcol 2004;6:1509-17.
20. Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145-9.
21. Korsmeyer RW, Peppas NA. Macromolecular and modeling aspects of swelling-controlled systems. In: Rosemam TS, Mansdorf SZ, editors. Controlled Release Delivery Systems. New York: Marcel Dekker; 1981. p. 77-90.
22. Ritger PL, Peppa NA. A simple equation of solute release 11 Fickian and anamalous fromswellable devices. J Control Release 1987;5:37-42.
23. Vandervoort J, Ludwig A. Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use. Eur J Pharm Biopharm 2004;57:251-61.
24. Shin DH, Glover BK, Cha SC, Kim YY, Kim C, Nguyen KD. Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy. Am J Ophthalmol 1999;127:511-5.
25. Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 2000;50:27-46.
26. Chen L, Tian Z, Du Y. Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices. Biomaterials 2004;25:3725-32.
27. Li Q, Wang J, Shahani S, Sun DD, Sharma B, Elisseeff JH, et al. Biodegradable andphotocrosslinkable polyphosphoester hydrogel. Biomaterials 2006;27:1027-34.
28. Davis KA, Anseth KS. Controlled release from crosslinked degradable networks. Crit Rev Ther Drug Carrier Syst 2002;19:385-423.
29. Lee KY, Yuk SH. Polymeric protein delivery systems. Prog Polym Sci 2007;32:669-97.
30. Coviello T, Matricardi P, Marianecci C, Alhaique F. Polysaccharide hydrogels formodifiedrelease formulations. J Control Release 2007; 119:5-24.
31. Jeong SH, Huh KM, Park K. Hydrogel Drug Delivery Systems, in Polymers in Drug Delivery. Boca Raton: CRC Press; 2006. p. 49-62.
32. Kamath KR, Park K. Biodegradable hydrogels in drug delivery. Adv Drug Deliv Rev 1993;11:59-84.
33. Hennink WE, van Nostrum CF. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 2002;54:13-36.
34. Jain D, Carvalho E, Banthia AK, Banerjee R. Development of polyvinyl alcohol-gelatin membranes for antibiotic delivery in the eye. Drug Dev Ind Pharm 2011;37:167-77.
35. Calvo P, Vila-Jato JL, Alonso MJ. Evaluation of cationic polymer-coated nano capsule as ocular drug carrier. Int J Pharm 1997;153:41-50.
36. Enríquez Salamanca A, Diebold Y, Calonge M, García-Vazquez C, Callejo S, Vila A, et al. Chitosan nanoparticles as a potential drug delivery system for the ocular surface: Toxicity, uptake mechanism and in vivo tolerance. Invest Opthalmol Vis Sci 2006;47:1416-25.
37. Department of Health. Indian Pharmacopoeia. Vol. 1and 2.Appendix I-X. New Delhi. Pub Controller of Publication; 1996. p. 110-52.