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Journal of Pharmaceutical Investigation

, Volume 45, Issue 1, pp 23–33 | Cite as

Oral lipid based multiparticulate pastilles: design and effect of pore former

  • Ashlesha P. PanditEmail author
  • Ganesh Divase
  • Tushar Chavan
  • Kishanchandra Khandelwal
Research Article
  • 81 Downloads

Abstract

The purpose of this research work was to design and develop droplet solidification apparatus for lipid based pastilles. Oral lipid based multiparticulate pastilles of solid lipid glycerol monostearate were formulated to control the release of highly water soluble drug metoprolol succinate. The apparatus was optimized at 14G needle size and metallic surface base plate cooled at 4 °C. Pastilles were evaluated for their size, shape, contact angle, density, flow properties, friability, crushing strength, drug content, thermal properties, in vitro and in vivo drug release. Pastilles were hemispherical in shape of size 3.1–4.3 mm. Contact angle was found to be more than 120°. Drug release was controlled for 8 h. Scanning electron microscopy study revealed the smooth external surface with pores to ingress dissolution media to enhance the drug release rate. Increased quantity of pore former enhanced the dissolution rate. Other operating variables like contact angle and height of needle from base plate were found to affect the size of pastilles. The dissolution of optimized batch of pastilles was best fitted to first order kinetic model. In vivo pharmacokinetic study showed correlation with in vitro drug release profile.

Keywords

Pastille Pellet Solid lipid glycerol monostearate Pore former Contact angle Crushing strength 

Notes

Acknowledgments

This article does not contain any studies with human and animal subjects performed by any of the authors. All authors (A. P. Pandit, G. Divase, T. Chavan, K. Khandelwal) declare that they have no conflict of interest. The authors are thankful to Mylan Laboratories Limited, Nasik, India for providing metoprolol succinate as gift sample. The authors are also grateful to Dr. S. S. Ambavade for his support for in vivo study and Dr. V. P. Chaudhari for guiding on analysis of plasma. Thanks are extended to Principal and Management of Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune, India.

References

  1. Abdul S, Chandewar A, Jaiswal S (2010) A flexible technology for modified-release drugs: multiple-unit pellet system (MUPS). J Controlled Release 147:2–16CrossRefGoogle Scholar
  2. Almeida PS, Blanco MJ, Otero SFJ (2005) Starch–dextrin mixtures as base excipients for extrusion–spheronization pellets. Eur J Pharm Biopharm 59:511–521CrossRefGoogle Scholar
  3. Almeida A, Possemiers S, Boone M, De Beer T, Quinten T, Van Hoorebeke L, Remon J, Vervaet C (2011) Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced via hot-melt extrusion. Eur J Pharm Biopharm 77:297–305CrossRefPubMedGoogle Scholar
  4. Cespi M, Bonacucina G, Misici-Falzi M, Golzi R, Boltri L, Palmieri G (2007) Stress relaxation test for the characterization of the viscoelasticity of pellets. Eur J Pharm Biopharm 67:476–484CrossRefPubMedGoogle Scholar
  5. Chakraborty S, Shukla D, Mishra B, Singh S (2009) Lipid- an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm 73:1–15CrossRefPubMedGoogle Scholar
  6. Djuris J, Nikolakakis I, Ibric S, Djuric Z, Kachrimanis K (2013) Preparation of carbamazepine–soluplus solid dispersions by hot-melt extrusion and prediction of drug–polymer miscibility by thermodynamic model fitting. Eur J Pharm Biopharm 84:228–237CrossRefPubMedGoogle Scholar
  7. Goyanes A, Souto C, Martínez-Pacheco R (2011) Co-processed MCC-Eudragit E excipients for extrusion–spheronization. Eur J Pharm Biopharm 79:658–663CrossRefPubMedGoogle Scholar
  8. Grassi M, Voinovich D, Moneghini M, Franceschinis E, Perissutti B, Filipovic-Grcic J (2003) Preparation and evaluation of a melt pelletised paracetamol/stearic acid sustained release delivery system. J Control Release 88:381–391CrossRefPubMedGoogle Scholar
  9. Gures S, Siepmann F, Siepmann J, Kleinebudde P (2012) Drug release from extruded solid lipid matrices: theoretical predictions and independent experiments. Eur J Pharm Biopharm 80:122–129CrossRefPubMedGoogle Scholar
  10. Hamdani J, Moes A, Amighi K (2006) Development and in vitro evaluation of a novel floating multiple unit dosage form obtained by melt pelletization. Int J Pharm 322:96–103CrossRefPubMedGoogle Scholar
  11. Kim J, Ulrich J (2003) Prediction of degree of deformation and crystallization time of molten droplets in pastillation process. Int J Pharm 257:205–215CrossRefPubMedGoogle Scholar
  12. Kojima M, Nakagami H (2002) Development of controlled release matrix pellets by annealing with micronized water-insoluble or enteric polymers. J Control Release 82:335–343CrossRefPubMedGoogle Scholar
  13. Kumar K, Shah MH, Ketkar A, Mahadik KR, Paradkar A (2004) Effect of drug solubility and different excipients on floating behaviour and release from glyceryl monooleate matrices. Int J Pharm 272:151–160. doi: 10.1016/j.ijpharm.2003.12.025 CrossRefGoogle Scholar
  14. Mathur V, Mudnaik R, Barde L, Roy A, Shivhare U, Bhusari K (2010) Formulation and evaluation of controlled release antibiotic biodegradable implants for post operative site delivery. Acta Pharm 60:111–117CrossRefPubMedGoogle Scholar
  15. Nandi U, Karmakar S, Das A, Ghosh B, Padman A, Chatterjee N, Pal T (2013) Pharmacokinetics, pharmacodynamics and toxicity of a combination of metoprolol succinate and telmisartan in Wistar albino rats: safety profiling. Regul Toxicol Pharmacol 65:68–78CrossRefPubMedGoogle Scholar
  16. Novoa G, Heinamaki J, Mirza S, Antikainen O, Colarte AI, Paz AS, Yliruusi J (2005) Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate. Eur J Pharm Biopharm 59:343–350CrossRefGoogle Scholar
  17. Ochoa L, Igartua M, Hernández RM, Gascón AR, Solinis MA, Pedraz JL (2011) Novel extended-release formulation of lovastatin by one-step melt granulation: in vitro and in vivo evaluation. Eur J Pharm Biopharm 77:306–312CrossRefPubMedGoogle Scholar
  18. Pandit AP, Mathur VB (2014) Formulation and development of two-compartment HPMC capsule for concurrent administration of drugs. Pharma Innov J 2(12):79–83Google Scholar
  19. Pandit AP, Shinde RD (2010) Development and in vitro evaluation of sustained release multiparticulate tablet of freely water soluble drug. Braz J Pharm Sci 46(3):463–471. doi: 10.1590/S1984-82502010000300009 CrossRefGoogle Scholar
  20. Passerini N, Perissutti B, Moneghini M, Voinovich D, Albertini B, Cavallari C, Rodriguez L (2002) Characterization of carbamazepine-gelucire 50/13 microparticles prepared by a spray-congealing process using ultrasounds. J Pharm Sci 91:699–707CrossRefPubMedGoogle Scholar
  21. Porter CJ, Charman WN (2001) In vitro assessment of oral lipid based formulations. Adv Drug Deliv Rev 50:S127–S147. doi: 10.1016/S0169-409X(01)00182-X CrossRefPubMedGoogle Scholar
  22. Prabhu S, Ortega M, Ma C (2005) Novel lipid-based formulations enhancing the in vitro dissolution and permeability characteristics of a poorly water-soluble model drug, piroxicam. Int J Pharm 301:209–216CrossRefPubMedGoogle Scholar
  23. Qi S, Deutsch D, Craig DQM (2008) An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres. Eur J Pharm Sci 97:3842–3854CrossRefGoogle Scholar
  24. Reitz C, Kleinebudde P (2007) Solid lipid extrusion of sustained release dosage forms. Eur J Pharm Biopharm 67:440–448CrossRefPubMedGoogle Scholar
  25. Rubinstein M (2000) Tablets. In: Aulton ME (ed) Pharmaceutics: the science of dosage form design. Churchill Livingstone, New York, p 305Google Scholar
  26. Shukla D, Chakraborty S, Singh S, Mishra B (2011) Pastillation: a novel technology for development of oral lipid based multiparticulate controlled release formulation. Powder Technol 209:65–72. doi: 10.1016/j.powtec.2011.02.006 CrossRefGoogle Scholar
  27. Shukla D, Chakraborty S, Mishra B (2012) In vitro and in vivo evaluation of multilayered pastilles for chronotherapeutic management of nocturnal asthma. Expert Opin Drug Deliv 9:9–18CrossRefPubMedGoogle Scholar
  28. Siepmann F, Muschert S, Flament M, Leterme P, Gayot A, Siepmann J (2006) Controlled drug release from gelucire-based matrix pellets: experiment and theory. Int J Pharm 317:136–143CrossRefPubMedGoogle Scholar
  29. Thies C, Ribeiro Dos Santos I, Richard J, Vande Velde V, Rolland H, Benoit J (2003) A supercritical fluid-based coating technology 1: process considerations. J Microencapsul 20:87–96CrossRefPubMedGoogle Scholar
  30. Windbergs M, Strachan C, Kleinebudde P (2009) Understanding the solid-state behaviour of triglyceride solid lipid extrudates and its influence on dissolution. Eur J Pharm Biopharm 71:80–87CrossRefPubMedGoogle Scholar
  31. Young C, Koleng J, McGinity J (2002) Production of spherical pellets by a hot-melt extrusion and spheronization process. Int J Pharm 242:87–92CrossRefPubMedGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2014

Authors and Affiliations

  • Ashlesha P. Pandit
    • 1
    Email author
  • Ganesh Divase
    • 1
  • Tushar Chavan
    • 1
  • Kishanchandra Khandelwal
    • 1
  1. 1.Department of PharmaceuticsJSPM’s Rajarshi Shahu College of Pharmacy and ResearchPuneIndia

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