FORMULATION AND EVALUATION OF CONTROLLED RELEASE MUCOADHESSIVE MATRIX TABLETS OF LEVAMISOLE: ASSEMENT OF PURIFIED FRUIT PULP POLYSACCHARIDE ISOLATED FROM AEGLE MARMELOS AS MUCOADHESIVE EXCIPIENT
Objective: Mucoadhesive tablets have been developed for Levamisole using natural mucoadhesive material such as purified polysaccharide isolated from
the ripe fruit pulp of Aegle marmelos. Lin (AMPS) and evaluate in-vitro, in-vivo mucoadhesive properties to assess its efficacy as mucoadhesive agent.
Method: The tablets were formulated with AMPS in different concentration employing wet granulation method. Pre-compression tests, tablet
parametric tests, swelling index and In-vitro drug release kinetics were performed. Optimization of formulation was done on the basis of controlled
and maximum amount of drug release with respect to time. In-vitro, ex-vivo evaluation of mucoadhesion was performed with all prepared formulation
but in-vivo evaluation was done by X-ray with optimized formulation (F40) in rabbit. Stability studies were carried out according to ICH guide line
with optimized formulation.
Results: The tensile strength, mucoadhesive strength and swelling index increase as the natural polymer concentration increase. The release
Kinetics and mechanism of release were calculated by fitting in-vitro release data in various models demonstrating that release. In vitro drug release
of the optimized batch (F40) was best fitted and explained by Korsemeyerâ€“Peppas and zero order drug release; (Rp=0.9891) and (Ro=0.9842)
showed highest linearity and n value 0.97>0.5<1. Hence, pattern of drug release by non-Fickian erosion controlled release. Studies of the optimized
formulation demonstrate no significant change in the tensile strength, mucoadhesive strength and drug assay.
Conclusion: These research outcomes clearly specify the potential of the AMPS to be used as mucoadhesive, release retardent natural material in
Keywords: Polysaccharide, Acrylamidopropylmethane sulfonic acid, Aegle marmelos, Levamisole, Mucoadhessive.
1. Morris GA. Polysaccharide drug delivery systems based on pectin and chitosan. Biotechnol Genet Eng Rev 2010;27:257-83.
2. Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 2009;71(3):505-18.
3. Morkhade DM, Fulzele SV, Satturwar PM, Joshi SB. Gum copal and gum damar: Novel matrix forming materials for sustained drug delivery. Indian J Pharm Sci 2006;68(1):53-8.
4. Jindal M, Kumar V, Ranaa V, Tiwarya AK. Aegle marmelos fruit pectin for food and pharmaceuticals: Physico-chemical, rheological and functional performance. Carbohydr Polym 2013;93(2):386-94.
5. Patil DN, Kulkarni AR, Patil BS. Fruit gum of Aegle marmelos as pharmaceutical aid. Int J Pharmacol 2010;6(1):68-71.
6. Vandamme TF, Demoustier M, Rollmann B. Quantitation of levamisole in plasma using high performance liquid chromatography. Eur J Drug Metab Pharmacokinet 1995;20(2):145-9.
7. Koyma K, Oshi T, Ishii A, Deguchi T. Levamisole: Metabolic fate of levamisole in rats, dogs and monkey. Oyo Yakuri 1983;26:869-76.
8. Adams JG. Pharmacokinetics of levamisole. J Rheumatol Suppl 1978;4:137-42.
9. Barker SA. The formation of aminorex in racehorses following levamisole administration. A quantitative and chiral analysis following synthetic aminorex or levamisole administration vs. aminorex-positive samples from the field: A preliminary report. J Vet Pharmacol Ther 2009;32(2):160-6.
10. Kumar MK, Suseela M. Phytochemical investigation and acute toxicity study of methanol extract of Bambusa vulgaris leaves. J Pharm Res 2011;4(2):403-5.
11. Singh AV, Nath LK. Evaluation of chemically modified hydrophobic sago starch as a carrier for controlled drug delivery. Saudi Pharm J 2013;21(2):193-200.
12. IP. Indian Pharmacopoeia. The Indian Pharmacopoeia Commission, Central Indian Pharmacopoeia Laboratory, Ministry of Health and Family Welfare, Govt. of India, Sector 23, Raj Nagar, Ghaziabad 201 002, India; 2007. p. 1516-7.
13. Shaikh DM, Shende MA, Shaikh AM. Formulation development and evaluation of gastro retentive mucoadhesive tablets using synthetic polymers. Int J Res Pharm Biomed Sci 2013;4(4):1264-71.
14. Manivannan R, Balasubramaniam A, Prem DC, Sandeep G, Rajkumar N. Formulation and in-vitro evaluation of mucoadhesive buccal tablets of diltiazem hydrochloride. Res J Pharm Technol 2008;1(4):478-80.
15. Sriamornsak P, Thirawong N, Weerapol Y, Nunthanid J, Sungthongjeen S. Swelling and erosion of pectin matrix tablets and their impact on drug release behavior. Eur J Pharm Biopharm 2007;67(1):211-9.
16. Ghosal K, Chakrabarty S, Nanda A. Hydroxypropyl methylcellulose in drug delivery. Pelagia Res Libr 2011;2(2):152-68.
17. Dash S, Murthy PN, Nath LK, Chowdhury P. Kinetic modelling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010;67(3):217-23.
18. Lehr CM, Joke L, Schacht EH, Junginger H E. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 1992;78(1):43-8.
19. Teng CL, Ho NF. Mechanistic studies in the simultaneous flow and adsorption of polymer-Coated latex particle on intestinal mucus. J Cont Release 1987;6(1):133-49.
20. Rao R, Buri KV. A novel in situ method to test polymers and coated micro particles for bioadhesion. Int J Pharm 1989;52:265-70.
21. Singh SK, Bothara SB, Singh S, Patel R, Dodia R. Formulation and evaluation of mucoadhesive tablet: Influece of some hydrophilic polymers on the release rate and in vitro evaluation. Intern J Pharm Sci Nanotechnol 2010;3(3):1111-21.
22. Jain SK, Agrawal GP, Jain NK. A novel calcium silicate based microspheres of repaglinide: In vivo investigations. J Control Release 2006;113(2):111-6.
23. Jinsixiaozao CV, Li J, Fan L, Ding S. Isolation, purification and structure of a new water soluble polysaccharide from Zizyphus jujube. Carbohydr Polym 2011;83:477-82.
24. SÃ¤kkinen M, Marvola J, Kanerva H, Lindevall K, Ahonen A, Marvola M. Are chitosan formulations mucoadhesive in the human small intestine? An evaluation based on gamma scintigraphy. Int J Pharm 2006;307(2):285-91.
25. Abrahamsson B, Alpsten M, Bake B, Larsson A, SjÃ¶gren J. In vitro and in vivo erosion of two different hydrophilic gel matrix tablets. Eur J Pharm Biopharm 1998;46(1):69-75.
26. Al-Taani BM, Tashtoush BM. Effect of microenvironment pH of swellable and erodable buffered matrices on the release characteristics of diclofenac sodium. AAPS PharmSciTech 2003;4(3):E43.
27. Hancock BC, Parks M. What is the true solubility advantage for amorphous pharmaceuticals? Pharm Res 2000;17(4):397-404.
28. Arora G, Malik K, Singh I. Formulation and evaluation of mucoadhesive matrix tablet of taro gum: Optimization using response surface methodology. Pol Med 2011;41(2):23-34.
29. Singh B, Chakkal SK, Ahuja N. Formulation and optimization of controlled release mucoadhesive tablets of atenolol using response surface methodology. AAPS PharmSciTech 2006;7(1):E3.
30. Ponchel G, Touchard F, Duchene D, Peppas NA. Bioadhesive analysis of controlled systems. I. fracture and interpenetration analysis in poly (acrylic acid) containing systems. J Cont Release 1987;5:129-41.
31. Singh B, Ahuja N. Development of controlled release bucoadhesive hydrophilic matrices of diltiazem hydrochloride: Optimization of bioadhesive, dissolution and diffusion parameters. Drug Dev Ind Pharm 2002;28(4):431-42.
32. Abrahamsson B, Alpsten M, Bake B, Larsson A, SjÃ¶gren J. In vitro and in vivo erosion of two different hydrophilic gel matrix tablets. Eur J Pharm Biopharm 1998;46(1):69-75.
33. Mughal MA, Iqbal Z, Neau SH. Guar gum, xanthan gum, and HPMC can define release mechanisms and sustain release of propranolol hydrochloride. AAPS PharmSciTech 2011;12(1):77-87.
34. Leung SH, Robinson JR. Polymer structure features contributing to mucoadhesion II. J Cont Release 1990;12:187-94.
35. Arora G, Malik K, Singh I, Arora S, Formulation and evaluation of controlled release mucoadhesive matrix tablets: Assessment of myrrh oleo gum resin as a natural pharmaceutical excipient. Int J Pharm Sci Drug Res 2011;3(2):84-8.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.