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Probing the effect of various lipids and polymer blends on clopidogrel encapsulated floating microcarriers

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Abstract

Background

Clopidogrel (CLOP) is an antiplatelet drug with poor solubility in intestinal fluid, which limits its bioavailability after oral administration.

Objectives

Current study focuses on developing site-specific floating microcarriers of CLOP using solvent diffusion evaporation method (SDEM) for retaining the drug in the stomach, thus improving the solubility of drug for better absorption.

Methods

SDEM was employed to formulate floating microcarriers using lipidic excipients, namely Gelucires (GL) to impart floating properties, in combination with ethyl cellulose as release retarding polymer.

Results

Prepared particles were 169 ± 6 μm to 375 ± 13 μm in size, whilst encapsulation efficiency was ranged from 39.6 ± 0.60% to 96.50 ± 3.50%. Electron micrographs depicted discrete spherical microcarriers with porous structure, which amplified with increasing HLB value of GL and concentration of Eudragit E100. FTIR study confirmed absence of major drug polymer interactions while DSC and XRD studies revealed the presence of non-crystalline nature of drug in all formulations. Drug release at pH 1.2 enhanced more than 2-folds with increasing HLB value with 32% cumulative drug release for GL 43/01 and 69% for GL 50/13. More interestingly, adding various proportions of Eudragit E100 to GL 43/01 based formulations resulted in increased drug release as high as 71%. In all formulations, the drug release followed diffusion dependent process.

Conclusion

It is envisaged that this formulation strategy for CLOP is promising and could possibly be tested in future for its in vivo performance.

Lipid based floating microcarriers of clopidogrel.

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References

  1. Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS PharmSciTech. 2009;10(3):1071–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Whitehead L, Fell J, Collett J, Sharma H, Smith A-M. Floating dosage forms: an in vivo study demonstrating prolonged gastric retention. J Control Release. 1998;55(1):3–12.

    CAS  PubMed  Google Scholar 

  3. Sungthongjeen S, Paeratakul O, Limmatvapirat S, Puttipipatkhachorn S. Preparation and in vitro evaluation of a multiple-unit floating drug delivery system based on gas formation technique. Int J Pharm. 2006;324(2):136–43. https://doi.org/10.1016/j.ijpharm.2006.06.002.

    Article  CAS  PubMed  Google Scholar 

  4. Shahzad Y, Saeed S, Ghori MU, Mahmood T, Yousaf AM, Jamshaid M, et al. Influence of polymer ratio and surfactants on controlled drug release from cellulosic microsponges. Int J Biol Macromol. 2018;109:963–70. https://doi.org/10.1016/j.ijbiomac.2017.11.089.

    Article  CAS  PubMed  Google Scholar 

  5. Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y. Hollow microspheres for use as a floating controlled drug delivery system in the stomach. J Pharm Sci. 1992;81(2):135–40.

    CAS  PubMed  Google Scholar 

  6. Sharma S, Pawar A. Low density multiparticulate system for pulsatile release of meloxicam. Int J Pharm. 2006;313(1):150–8.

    CAS  PubMed  Google Scholar 

  7. Iannuccelli V, Coppi G, Bernabei M, Cameroni R. Air compartment multiple-unit system for prolonged gastric residence. Part I. formulation study. Int J Pharm. 1998;174(1):47–54.

    CAS  Google Scholar 

  8. Streubel A, Siepmann J, Bodmeier R. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release. Eur J Pharm Sci. 2003;18(1):37–45.

    CAS  PubMed  Google Scholar 

  9. Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery systems: a review. AAPS PharmSciTech. 2005;6(3):E372–E90. https://doi.org/10.1208/pt060347.

    Article  PubMed  PubMed Central  Google Scholar 

  10. DrugBank A. Open data drug & drug target database. Accessed online march. 2013;19.

  11. Kolbe I, Vikmon M, Gerlóczy A, Szejtli J. Preparation and characterization of clopidogrel/DIMEB complex. J Incl Phenom Macrocycl Chem. 2002;44(1):183–4.

    CAS  Google Scholar 

  12. Takahashi M, Pang H, Kawabata K, Farid NA, Kurihara A. Quantitative determination of clopidogrel active metabolite in human plasma by LC–MS/MS. J Pharm Biomed Anal. 2008;48(4):1219–24.

    CAS  PubMed  Google Scholar 

  13. Tan C, Degim İT. Development of sustained release formulation of an antithrombotic drug and application of fuzzy logic. Pharm Dev Technol. 2012;17(2):242–50.

    CAS  PubMed  Google Scholar 

  14. Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348(9038):1329–39.

    Google Scholar 

  15. Luo J-C. Gastroprotective strategy in aspirin users. J Chin Med Assoc. 2009;72(7):343–5.

    CAS  PubMed  Google Scholar 

  16. Patel PR, Roy SB, Kothari JS. Modified release clopidogrel formulation. Google patents; 2007.

  17. Jagtap Y, Bhujbal R, Ranade A, Ranpise N. Effect of various polymers concentrations on physicochemical properties of floating microspheres. Indian J Pharm Sci. 2012;74(6):512–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Dhaliwal S, Jain S, Singh HP, Tiwary A. Mucoadhesive microspheres for gastroretentive delivery of acyclovir: in vitro and in vivo evaluation. AAPS J. 2008;10(2):322–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Nila M, Sudhir M, Cinu T, Aleykutty N, Jose S. Floating microspheres of carvedilol as gastro retentive drug delivery system: 32 full factorial design and in vitro evaluation. Drug Deliv. 2014;21(2):110–7.

    CAS  PubMed  Google Scholar 

  20. Ammar HO, Ghorab MM, Mahmoud AA, Noshi SH. Formulation of risperidone in floating microparticles to alleviate its extrapyramidal side effects. Futur J Pharm Sci. 2016;2(2):43–59.

    Google Scholar 

  21. Ravi T. High performance liquid chromatographic determination of aspirin and clopidogrel in tablets. Indian J Pharm Sci. 2007;69(1):123.

    Google Scholar 

  22. Ranjha NM, Khan IU, Naseem S. Encapsulation and characterization of flurbiprofen loaded poly (є-caprolactone)–poly (vinylpyrrolidone) blend micropheres by solvent evaporation method. J Sol-Gel Sci Technol. 2009;50(3):281–9.

    CAS  Google Scholar 

  23. Rao MEB, Swain S, Patra CN, Sruti J, Patra S. Development and in vitro evaluation of floating multiparticulate system of repaglinide. FABAD J Pharm Sci. 2011;36(2):75–92.

    Google Scholar 

  24. Passerini N, Perissutti B, Moneghini M, Voinovich D, Albertini B, Cavallari C, et al. Characterization of carbamazepine–Gelucire 50/13 microparticles prepared by a spray-congealing process using ultrasounds. J Pharm Sci. 2002;91(3):699–707.

    CAS  PubMed  Google Scholar 

  25. Patel A, Ray S, Thakur RS. Invitro evaluation and optimization of controlled release floating drug delivery system of metformin hydrochloride. DARU J Pharm Sci. 2006;14(2):57–64.

    CAS  Google Scholar 

  26. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123–33.

    CAS  PubMed  Google Scholar 

  27. Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145–9.

    CAS  PubMed  Google Scholar 

  28. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25–35.

    CAS  Google Scholar 

  29. Maghsoodi M. Physicomechanical properties of naproxen-loaded microparticles prepared from Eudragit L100. AAPS PharmSciTech. 2009;10(1):120–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Mastiholimath V, Dandagi P, Gadad A, Mathews R, Kulkarni A. In vitro and in vivo evaluation of ranitidine hydrochloride ethyl cellulose floating microparticles. J Microencapsul. 2008;25(5):307–14.

    CAS  PubMed  Google Scholar 

  31. Singh V, Chaudhary AK. Preparation of Eudragit E100 microspheres by modified solvent evaporation method. Acta Pol Pharm. 2011;68(6):975–80.

    CAS  PubMed  Google Scholar 

  32. Nepal PR, Chun M-K, Choi H-K. Preparation of floating microspheres for fish farming. Int J Pharm. 2007;341(1–2):85–90.

    CAS  PubMed  Google Scholar 

  33. Reddy BP, Dorle A, Krishna D. Albumin microspheres: effect of process variables on size distribution and in vitro release. Drug Dev Ind Pharm. 1990;16(11):1791–803.

    CAS  Google Scholar 

  34. Jain SK, Gupta A. Development of Gelucire 43/01 beads of metformin hydrochloride for floating delivery. AAPS PharmSciTech. 2009;10(4):1128–36. https://doi.org/10.1208/s12249-009-9302-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chauhan B, Shimpi S, Mahadik K, Paradkar A. Preparation and evaluation of floating risedronate sodium–Gelucire® 43/01 formulations. Drug Dev Ind Pharm. 2005;31(9):851–60.

    CAS  PubMed  Google Scholar 

  36. Patra CN, Priya R, Swain S, Jena GK, Panigrahi KC, Ghose D. Pharmaceutical significance of Eudragit: a review. Futur J Pharm Sci. 2017;3:33–45.

    Google Scholar 

  37. Chauhan B, Shimpi S, Mahadik K, Paradkar A. Preparation and evaluation of floating risedronate sodium Gelucire 39/01 matrices. Acta Pharm (Zagreb, Croatia). 2004;54(3):205–14.

    CAS  Google Scholar 

  38. Emeje M, Kunle O, Ofoefule S. Compaction characteristics of ethylcellulose in the presence of some channeling agents: technical note. AAPS PharmSciTech. 2006;7(3):E18–21.

    PubMed Central  Google Scholar 

  39. Agrawal AM, Manek RV, Kolling WM, Neau SH. Studies on the interaction of water with ethylcellulose: effect of polymer particle size. AAPS PharmSciTech. 2003;4(4):469–79.

    PubMed Central  Google Scholar 

  40. Saravanan M, Anupama B. Development and evaluation of ethylcellulose floating microspheres loaded with ranitidine hydrochloride by novel solvent evaporation-matrix erosion method. Carbohydr Polym. 2011;85(3):592–8.

    CAS  Google Scholar 

  41. Abdul Althaf S, Sailaja P, Ashwin Kumar M. Formulation, evaluation and mathematical modelling of clopidogrel bisulphate & aspirin immediate release bilayer tablets. Pharm Anal Acta. 2012;3:194.

    Google Scholar 

  42. Priya JK, Kumar PP, Begum SS. Formulation and evaluation of clopidogrel bisulphate transdermal patches using vegetable oils as permeation enhancer. Int J Pharm Sci Res. 2014;5(2):473.

    Google Scholar 

  43. Bond L, Allen S, Davies MC, Roberts CJ, Shivji AP, Tendler SJB, et al. Differential scanning calorimetry and scanning thermal microscopy analysis of pharmaceutical materials. Int J Pharm. 2002;243(1):71–82. https://doi.org/10.1016/S0378-5173(02)00239-9.

    Article  CAS  PubMed  Google Scholar 

  44. Singh SK, Som S, Shankhwar U. Formulation and optimization of solid dispersion of Clopidogrel with PEG 6000. 2011.

  45. Lee J, Oh YJ, Lee SK, Lee KY. Facile control of porous structures of polymer microspheres using an osmotic agent for pulmonary delivery. J Control Release. 2010;146(1):61–7.

    CAS  PubMed  Google Scholar 

  46. Li J, Jiang G, Ding F. Effects of polymer degradation on drug release from PLGA-mPEG microparticles: a dynamic study of microparticle morphological and physicochemical properties. J Appl Polym Sci. 2008;108(4):2458–66.

    CAS  Google Scholar 

  47. Adeyeye CM, Price JC. Development and evaluation of sustained-release ibuprofen–wax microspheres. II. In vitro dissolution studies. Pharm Res. 1994;11(4):575–9.

    CAS  PubMed  Google Scholar 

  48. Jung J-Y, Yoo SD, Lee S-H, Kim K-H, Yoon D-S, Lee K-H. Enhanced solubility and dissolution rate of itraconazole by a solid dispersion technique. Int J Pharm. 1999;187(2):209–18.

    CAS  PubMed  Google Scholar 

  49. Jijun F, Lishuang X, Xiaoli W, Shu Z, Xiaoguang T, Xingna Z, et al. Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion. Drug Dev Ind Pharm. 2011;37(8):934–44.

    PubMed  Google Scholar 

  50. Mohammadi-Samani S, Boostanian A. The effect of HLB on the release profile of atenolol from ethyl cellulose-coated tablets. Iran J Pharm Res. 2010:145–8.

  51. Basak SC, Kumar KS, Ramalingam M. Design and release characteristics of sustained release tablet containing metformin HCl. Rev Bras Ciênc Farm. 2008;44(3):477–83.

    CAS  Google Scholar 

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Acknowledgements

Authors acknowledge the kind support of Saffron Pharmaceutical (Pvt.) Ltd. Faisalabad, Pakistan to complete this research work.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan

    Saba Irshad, Ikram Ullah Khan, Syed Haroon Khalid, Sajid Asghar, Muhammad Irfan & Ikrima Khalid

  2. Department of Physics, Government College University Faisalabad, Faisalabad, Pakistan

    Nadeem Sabir & Adnan Ali

  3. Department of Materials Engineering, School of Chemical and Materials Engineering (SCME), National University of Sciences and Technology (NUST), Islamabad, Pakistan

    Ahmad Nawaz Khan

  4. Drug Delivery Research Group, Department of Pharmacy, COMSATS University Islamabad (CUI), Lahore Campus, Lahore, Pakistan

    Abid Mehmood Yousaf, Talib Hussain & Yasser Shahzad

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  1. Saba Irshad
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Correspondence to Ikram Ullah Khan or Yasser Shahzad.

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Irshad, S., Khan, I.U., Khalid, S.H. et al. Probing the effect of various lipids and polymer blends on clopidogrel encapsulated floating microcarriers. DARU J Pharm Sci 27, 571–582 (2019). https://doi.org/10.1007/s40199-019-00285-0

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