Dual buoyant/mucoadhesive macroporous polypropylene microparticles for gastric delivery of repaglinide

Mahmoud Eid Soliman, Enas M Elmowafy, Abdulfattah Almogerbi, samar holayel, Abdelhameed A ElShamy


Preparation and characterization of dual buoyant/mucoadhesive polypropylene microparticles (MPs) loaded with repaglinide (REP) for gastric drug delivery in order to augment the weak mucoadhesion in the stomach.

Porous foam powder MPs were prepared using coating polymers with variable permeability (Eudragit L100, Eudragit RSPO) alone or in combination by the soaking method. Thiolated Eudragit L100 (Eudragit L100-SH) was also synthesized and tried in an attempt to enhance the mucoadhesive properties of MPs. All formulae were characterized for their yield, flow properties, particle size, encapsulation efficiency (EE %), morphology, and drug release and its mechanistics. Possible interactions inside MPs matrix were also elucidated using FTIR study. The suitability of the selected formulae for gastroretention was evaluated by in vitro buoyancy and ex-vivo mucoadhesion studies.

All REP-loaded MPs demonstrated a passable powder flow, high yield values, promising floatation and mucoadhesion. Encapsulation efficiency % values were nearly tripled upon addition of Eudragit polymers. Compared to the Eudragit free REP loaded foam powder, all formula showed more sustained release features. Eudragit L100-SH was synthesized and confirmed by FTIR. Furthermore, its incorporation, alone or in combination, exhibited a significant increase in mucoadhesion strength compared to the unmodified one.

Dual buoyant/mucoadhesive MPs loaded with REP encourage planning for future in-vivo performance studies for the management of diabetes.


Dual buoyant/mucoadhesive system; polypropylene foam powder; thiolated-Eudragit L100; Repaglinide

Full Text:



  1. Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT. Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems.. Drug Deliv 2010 Oct;18(2):97-110. PubMed PMID: 20958237. doi: 10.3109/10717544.2010.520354.
  2. Shaikh R, T R R S . Mucoadhesive drug delivery systems. Journal of Pharmacy and Bioallied Sciences;2011(3).
  3. Quan JS. pH-sensitive and mucoadhesive thiolated Eudragit-coated chitosan microspheres. International journal of pharmaceutics. 2008(359):205-210. PMID:18490120. doi: 10.1016/j.ijpharm.2008.04.003.
  4. Bravo-Osuna I, Vauthier C, Farabollini A, Palmieri GF, Ponchel G. Mucoadhesion mechanism of chitosan and thiolated chitosan-poly(isobutyl cyanoacrylate) core-shell nanoparticles.. Biomaterials 2007 Jan;28(13):2233-2243.PubMed PMID: 17261330. doi: 10.1016/j.biomaterials.2007.01.005.
  5. Park H, Robinson JR. Mechanisms of mucoadhesion of poly (acrylic acid) hydrogels. Pharmaceutical research. Pharm Res 1987;4(6):457-464. PubMed PMID: 3508557.
  6. Deshpande A. Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug Development and Industrial. 1996;22(6):531-539.
  7. Streubel A, Siepmann J, Bodmeier R. Drug delivery to the upper small intestine window using gastroretentive technologies. Current opinion in pharmacology. Curr Opin Pharmacol 2006;6(5):501-508. PubMed PMID: 16890020. doi: 10.1016/j.coph.2006.04.007.
  8. Streubel A, Siepmann J, Bodmeier R. Floating microparticles based on low density foam powder. International journal of pharmaceutics;2002(241):279-292.
  9. Streubel A, Siepmann J, Bodmeier R. Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles. Journal of microencapsulation;2003(20):329-347. PubMed PMID: 12881114. doi: 10.1080/0265204021000058384.
  10. Jain SK. Calcium silicate based microspheres of repaglinide for gastroretentive floating drug delivery: Preparation and in vitro characterization. Journal of controlled release 2005 Oct;2005(107):300-309. PubMed PMID: 16095748. doi: 10.1016/j.jconrel.2005.06.007.
  11. Adibkia K, Hamedeyazdan S, Javadzadeh Y. Drug release kinetics and physicochemical characteristics of floating drug delivery systems. Expert opinion on drug delivery. Expert Opin Drug Deliv 2011;8(7):891-903. PubMed PMID: 21506906. doi: 10.1517/17425247.2011.574124.
  12. Sato Y. vitro evaluation of floating and drug releasing behaviors of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method. European journal of pharmaceutics and biopharmaceutics. Eur J Pharm Biopharm 2004;57(2):235-243. PubMed PMID: 15018980. doi: 10.1016/S0939-6411(03)00185-1.
  13. Dumitriu S, editor . Polymeric biomaterials, revised and expanded. CRC Press; 2001.
  14. Solstad RG, Li C, Isaksson J, Johansen J, Svenson J, Stensvåg K, et al. Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications. PloS; 2014. PubMed PMID: 25382976. doi: 10.2147/IJN.S66300.
  15. Quan JS, Jiang HL, Choi YJ, Yoo MK, Cho CS. Thiolated Eudragit-coated chitosan microspheres as an oral drug delivery system. InKey Engineering Materials 2007 (Vol;342:445-448.
  16. Rawat MK, Jain A, Mishra A, Muthu MS, Singh S. Development of repaglinide loaded solid lipid nanocarrier: selection of fabrication method.. Curr Drug Deliv 2010;7(1):44-50. PubMed PMID: 20044909.
  17. Baskar GV, Narayanan N, Gaikwad R, Abdul S. Formulation and evaluation of Gastro-retentive floating Multi-particulate system of metoprolol tartarate. Tropical Journal of Pharmaceutical Research 2010;2010(9).
  18. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm;2010(67):2010-67.
  19. Elmowafy E, Osman R. El-Shamy AE, Awad GA. Nasal polysaccharides-glucose regulator microparticles: Optimization, tolerability and antidiabetic activity in rats. Carbohydrate polymers. ;108:257-65.
  20. Zhu Z. A simple method to improve the dissolution of repaglinide and exploration of its mechanism. asian journal of pharmaceutical sciences. 2014;9(4):218-225.
  21. Sher P. density porous carrier: drug adsorption and release study by response surface methodology using different solvents. International journal of pharmaceutics 2006 Sep;2007(331):72-83. PubMed PMID: 17030470. doi: 10.1016/j.ijpharm.2006.09.013.
  22. Singh A, Pathak D, Pathak K. Use of Microporous Accurel MP1000 for Duodenal Delivery of Secnidazole: A High dose, gastric pH unstable drug. International Journal of Drug Delivery Technology;2010(2):26-34.
  23. Gupta R. Formulation and evaluation of novel stomach specific floating microspheres bearing famotidine for treatment of gastric ulcer and their radiographic study. Asian Pacific Journal of Tropical Biomedicine;2014(4):729-735.
  24. Lee WJ. Induction of Th1 polarized immune responses by thiolated Eudragit-coated F4 and F18 fimbriae of enterotoxigenic Escherichia coli. European journal of pharmaceutics and biopharmaceutics. Eur J Pharm Biopharm 2011;79(2):226-231. PubMed PMID: 21571066. doi: 10.1016/j.ejpb.2011.04.016.
  25. Lee WJ. Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice. European journal of pharmaceutics and biopharmaceutics. Eur J Pharm Biopharm 2012;81(1):43-48. PubMed PMID: 22306699. doi: 10.1016/j.ejpb.2012.01.010.
  26. Siepmann J, Peppas N. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Advanced drug delivery reviews. Adv Drug Deliv Rev 2012;64(2-3):163-174. PubMed PMID: 11369079.
  27. El-Kamel AH, Sokar MS. Al Gamal SS, Naggar VF. Preparation and evaluation of ketoprofen floating oral delivery system. International journal of 2001 Jun;pharmaceutics(220):2001-220. PubMed PMID: 11376963.
  28. Lekshmi UD, Poovi G, Reddy PN. In-vitro observation of repaglinide engineered polymeric nanoparticles. Dig J Nanomater Bios;2012(7):1-18.
  29. Sharma M, Sharma V, Panda AK, Majumdar DK. Development of enteric submicron particle formulation of papain for oral delivery.. Int J Nanomedicine 2011 Sep;6(6):2097-2111. PubMed PMID: 22114474. doi: 10.2147/IJN.S23985.
  30. Verma A, Pandit JK. Rifabutin-loaded floating gellan gum beads: effect of calcium and polymer concentration on incorporation efficiency and drug release. Tropical Journal of Pharmaceutical Research 2011:2011-10.
  31. Mukhopadhyay HK. Preparation and characterization of polymethacrylate-based matrix microspheres of carbamazepine using solvent evaporation method. Farmacia;2014(62):137-158.
  32. Devasahayam S, Sahajwalla V, Sng M. Investigation into Failure in Mining Wire Ropes—Effect of Crystallinity.Open. Journal of Organic Polymer Materials:2013-3. doi: 10.4236/ojopm.2013.32006..
  33. Jain SK. Lectin conjugated gastro-retentive microspheres of amoxicillin for effective treatment of Helicobacter pylori. CURRENT SCIENCE;2014(106):2014-106.
  34. Rathore S, Ram A. Porous microsphere of 5-Flouru uracil: a tool for site specific drug delivery in gastric cancer. 2011;5. [Google Scholar]
  35. Bernkop-Schnurch A, Hornof M, Guggi D. Thiolated chitosans. European journal of pharmaceutics and biopharmaceutics. Eur J Pharm Biopharm 2004;57(1):9-17. PubMed PMID: 14729077.


  • There are currently no refbacks.

Copyright (c) 2016 Mahmoud Eid Soliman, Enas M Elmowafy, Abdulfattah Almogerbi, samar holayel, Abdelhameed A ElShamy

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

               AR Journals

18K, Street 1st, Gaytri Vihar, Pinto Park, Gwalior, M.P. India

Copyright@arjournals.org (Design) 2009-2021


Follow @arjournals on Twitter