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Melt-in-Mouth Pellets of Fexofenadine Hydrochloride Using Crospovidone as an Extrusion–Spheronisation Aid

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Abstract

Microcrystalline cellulose (MCC) is well established as an extrusion spheronisation aid for the preparation of pellets. Crospovidone (Polyplasdone® XL-10) is compared with microcrystalline cellulose for the preparation of melt-in-mouth pellets. Taste-masked fexofenadine hydrochloride was incorporated in the melt-in-mouth formulation. Crospovidone was found to be well suited as extrusion–spheronisation aid for the preparation of melt-in-mouth pellets. The great advantage of crospovidone is, however, the disintegrating properties of the pellets after only a short time of exposure to liquid. Crospovidone was successfully employed as an extrusion–spheronisation aid to produce melt-in-mouth pellets obviating the need of a traditional extrusion–spheronisation aid, MCC. Dual properties of Crospovidone were explored viz. as an extrusion–spheronisation aid and a disintegrant.

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References

  1. Law M, Deasy P. Use of hydrophilic polymers with microcrystalline cellulose to improve extrusion – spheronization. Euro J Pharm Biopharm. 1998;45:57–65.

    Article  CAS  Google Scholar 

  2. Lustig-Gustafsson C, Kaur JH, Podczeck F, Newton JM. The influence of water content and drug solubility on the formulation of pellets by extrusion and spheronization. Eur J Pharm Sci. 1999;8:147–52.

    Article  CAS  PubMed  Google Scholar 

  3. Kleinebudde P. Shrinking and swelling properties of pellets containing microcrystalline cellulose and low substituted hydroxypropylcellulose: II. Swelling properties. Int J Pharm. 1994;109:221–7.

    Article  CAS  Google Scholar 

  4. Schroder M, Kleinebudde P. Development of disintegrating pellets obtained from extrusion/spheronization. Pharm Sci. 1995;1:415–8.

    Google Scholar 

  5. Lindner H, Kleinebudde P. Use of powdered cellulose for the production of pellets by extrusion/spheronization. J Pharm Pharmacol. 1994;46:2–7.

    CAS  PubMed  Google Scholar 

  6. Millili GP, Schwartz JB. The strength of microcrystalline cellulose pellets—the effect of granulating with water ethanol mixtures. Drug Dev Ind Pharm. 1990;16:1411–26.

    Article  CAS  Google Scholar 

  7. Okada S, Nakahara H, Isaka H. Adsorption of drugs on microcrystalline cellulose suspended in aqueous solutions. Chem Pharm Bull. 1987;35:761–8.

    CAS  Google Scholar 

  8. Basit AW, Newton JM, Lecey LF. Formulation of ranitidine pellets by extrusion/spheronization with a little and with no microcrystalline cellulose. Pharm Dev Technol. 1999;4:499–505.

    Article  CAS  PubMed  Google Scholar 

  9. Liew CV, Josephine LG, Soh LP, Heng PW. Functionality of cross-linked polyvinylpyrrolidone as a spheronization aid: a promising alternative to microcrystalline cellulose. Pharm Res. 2005;22:1387–98.

    Article  CAS  PubMed  Google Scholar 

  10. Bornhoft M, Thommes M, Kleinebudde P. Preliminary assessment of carrageenan as excipient for extrusion/spheronization. Eur J Pharm Biopharm. 2005;59:127–31.

    Article  CAS  PubMed  Google Scholar 

  11. Thommes M, Blaschek W, Kleinebudde P. Effect of drying on extruded pellets based on κ – carrageenan. Eur J Pharm Sci. 2007;31:112–8.

    Article  CAS  PubMed  Google Scholar 

  12. Thommes M, Kleinebudde P. Use of κ – carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronization. I. Influence of type and fraction of filler. Eur J Pharm Biopharm. 2006;63:59–67.

    Article  CAS  PubMed  Google Scholar 

  13. Thommes M, Kleinebudde P. Use of κ – carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronization. II. Influence of drug and filler type. Eur J Pharm Biopharm. 2006;63:68–75.

    Article  CAS  PubMed  Google Scholar 

  14. Steckel H, Mindermann-Nogly F. Production of chitosan pellets by extrusion/spheronization. Eur J Pharm Biopharm. 2004;57:107–14.

    Article  CAS  PubMed  Google Scholar 

  15. Chatchawalsaisin J, Podczeck F, Newton JM. The influence of chitosan and sodium alginate and formulation variables on the formation and drug release from pellets prepared by extrusion/spheronization. Int J Pharm. 2004;275:41–60.

    Article  CAS  PubMed  Google Scholar 

  16. Santos H, Veiga F, Pina M, Podczeck F, Sausa J. Physical properties of chitosan pellets produced by extrusion – spheronization: influence of formulation variables. Int J Pharm. 2002;246:153–69.

    Article  CAS  PubMed  Google Scholar 

  17. Agrawal AM, Manek RV, Kolling WM, Neau SH. Water distribution studies within microcrystalline cellulose and chitosan using differential scanning calorimetry and dynamic vapour sorption analysis. J Pharm Sci. 2004;93(7):1766–79.

    Article  CAS  PubMed  Google Scholar 

  18. Tho I, Sande SA, Kleinebudde P. Pectinic acid, a novel excipient for production of pellets by extrusion/spheronization: preliminary studies. Eur J Pharm Biopharm. 2002;54:95–9.

    Article  CAS  PubMed  Google Scholar 

  19. Tho I, Sande SA, Kleinebudde P. Disintegrating pellets from a water-insoluble pectin derivative produced by extrusion/spheronization. Eur J Pharm Biopharm. 2003;56:371–80.

    Article  CAS  PubMed  Google Scholar 

  20. Tho T, Kleinebudde P, Sande SA. Extrusion/spheronization of pectin-based formulations. I. Screening of important factors. AAPS PharmSciTech. 2002;2(4):26.

    Article  Google Scholar 

  21. Mehta KA, Kislalioglu MS, Phuapradit W, Malick AW, Shah NH. Release performance of a poorly soluble drug from a novel, Eudragit®- based multi –unit erosion matrix. Int J Pharm. 2001;213:7–12.

    Article  CAS  PubMed  Google Scholar 

  22. Chatlapalli R, Rohera BD. Physical characterization of HPMC and HEC and investigation of their use as pelletisation aids. Int J Pharm. 1998;161:179–93.

    Article  CAS  Google Scholar 

  23. Howard MA, Neau SH, Sack MJ. PEO and MPEG in high drug load extruded and spheronised beads that are devoid of MCC. Int J Pharm. 2006;307:66–76.

    Article  CAS  PubMed  Google Scholar 

  24. Almeida S, Prieto J, Mendez B, Espinar O. Starch – dextrin mixtures as base excipients for extrusion-spheronization pellets. Eur J Pharm Biopharm. 2005;59:511–21.

    Article  Google Scholar 

  25. Duki A, Mens R, Adriaensens P, Foreman C, Gelan J, Remon JP, et al. Development of starch based pellets via extrusion/spheronization. Eur J Pharm Biopharm. 2007;66:83–94.

    Article  Google Scholar 

  26. Chui CW, Henley M, Paul A. Inventors Process for making amylase resistant starch from high amylose starch. U.S. Patent 5,281,276, 1994.

  27. International Specialty Products, Technical profile: Crospovidone.

  28. Kornblum SS, Stoopak SB. A new tablet disintegrating agent: crosslinked Polyvinylpyrrolidone. J Pharm Sci. 1973;62:43–9.

    Article  CAS  PubMed  Google Scholar 

  29. Rudnic EM, Lausier JM, Chilamkurti RN, Rhodes CT. Studies of the utility of cross linked polyvinylpolypyrrolidine as a tablet disintegrant. Drug Dev Ind Pharm. 1980;6:291–309.

    Article  CAS  Google Scholar 

  30. Gordon MS, Chowhan ZT. Effect of tablet solubility and hygroscopicity on disintegrant efficiency in direct compression tablets in terms of dissolution. J Pharm Sci. 1987;76:907–9.

    CAS  PubMed  Google Scholar 

  31. Gordon MS, Rudraraju VS, Dani K, Chowhan ZT. Effect of the mode of super disintegrant incorporation on dissolution in wet granulated tablets. J Pharm Sci. 1993;82:220–6.

    Article  CAS  PubMed  Google Scholar 

  32. Schiermeier S, Schmidt PC. Fast dispersible ibuprofen tablets. Eur J Pharm Sci. 2002;15(3):295–305.

    Article  CAS  PubMed  Google Scholar 

  33. FAO/WHO. Evaluation of certain food additives and contaminants. Twenty-seventh report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser (1983) No. 696.

  34. Fielden KE, Newton JM, O’Brien P, Rowe RC. Thermal studies of the interaction of water and microcrystalline cellulose. J Pharm Pharmacol. 1988;40:674–8.

    CAS  PubMed  Google Scholar 

  35. Markham A, Wagstaff AJ. Fexofenadine. Drugs. 1998;55(2):269–74.

    Article  CAS  PubMed  Google Scholar 

  36. Simpson A, Jarvis B. Fexofenadine: a review of its use in management of seasonal allergic rhinitis and chronic idiopathic urticaria. Drugs. 2000;59(2):301–21.

    Article  CAS  PubMed  Google Scholar 

  37. O’Neil MJ, Smith A, Heckelman PE, Budavari S, editors; The Merck Index: an encyclopedia of chemicals, drugs and biologicals, 13th Edn. Merck, New Jersey; 2001, 4097pp.

  38. Buhler V. Polyvinylpyrrolidone excipients for pharmaceuticals. New York: Springer; 2005. 150pp.

    Google Scholar 

  39. Tokuyama E, Shibasaki T, Kawabe H, Mukai J, Okada S, Uchida T. Bitterness suppression of BCAA solutions by L-ornithine. Chem Pharm Bull. 2006;54:1288–92.

    Article  CAS  PubMed  Google Scholar 

  40. Erkoboni DF. Extrusion/spheronization. In: Ghebre-Sellasie I, Martin C, editors. Pharmaceutical Extrusion Technology. New York: Marcel Dekker; 2003. p. 277–322.

    Google Scholar 

  41. Malinowski HJ, Smith WE. Use of factorial design to evaluate granulations prepared by spheronization. J Pharm Sci. 1975;64:1688–92.

    Article  CAS  PubMed  Google Scholar 

  42. O’Connor RE, Schwartz JB. Extrusion and spheronization technology. In: Ghebre-Sellasie I, editor. Pharmaceutical Pelletization Technology. New York: Marcel Dekker; 1989. p. 187–216.

    Google Scholar 

  43. Zhang G, Schwartz JB, Schnaare RL, Wigent RJ, Sugita ET. Bead coating: II. effect of spheronization technique on dissolution from coated spheres. Drug Dev Ind Pharm. 1991;17:817–30.

    Article  CAS  Google Scholar 

  44. Albertini B, Cavallari C, Passerini N, Voinovich D, Gonzalez-Rodriguez ML, Magarotto L, et al. Characterization and taste-masking evaluation of acetaminophen granules: comparison between different preparation methods in a high shear mixer. Eur J Pharm Sci. 2004;21:295–303.

    Article  CAS  PubMed  Google Scholar 

  45. Staniforth JN. Powder flow. In: Aulton ME, editor. Pharmaceutics: the science of dosage form design. London: Churchill Livingstone; 1988. p. 600–15.

    Google Scholar 

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Acknowledgement

We would like to express our gratitude to ISP Limited and Signet Chemicals Corporation for the gift samples of Crospovidone and Avicel® PH-101, respectively. We also would like to thank Bajaj Healthcare, University Grant Commission and Department of Biotechnology for providing financial support to carry out the project.

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Authors and Affiliations

  1. Department Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, 400019, India

    Satishkumar P. Jain, Dharmini C. Mehta, Sejal P. Shah, Pirthi Pal Singh & Purnima D. Amin

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  1. Satishkumar P. Jain
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  2. Dharmini C. Mehta
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  3. Sejal P. Shah
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  4. Pirthi Pal Singh
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  5. Purnima D. Amin
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Correspondence to Purnima D. Amin.

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Jain, S.P., Mehta, D.C., Shah, S.P. et al. Melt-in-Mouth Pellets of Fexofenadine Hydrochloride Using Crospovidone as an Extrusion–Spheronisation Aid. AAPS PharmSciTech 11, 917–923 (2010). https://doi.org/10.1208/s12249-010-9443-7

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