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In Vivo Characterization of Oral Multiparticulate Systems

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Book cover Multiparticulate Drug Delivery

Part of the book series: Advances in Delivery Science and Technology ((ADST))

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Abstract

Formulation development of pharmaceutical multiparticulates requires in vivo performance validation which can be achieved with real-time imaging techniques such as gamma scintigraphy and magnetic resonance imaging either as stand-alone methods or in combination with complementary investigations such as pharmacokinetic sampling and pH and temperature measurements using sophisticated swallowable electronic devices.

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References

  1. Wilding IR. Evolution of the Biopharmaceutics classification system to oral modified release formulations; what do we need to consider? Eur J Pharm Sci. 1999;8:157–9.

    Article  CAS  PubMed  Google Scholar 

  2. Channer KS, Virjee JP. The effect of size and shape of tablets on their esophageal transit. J Clin Pharmacol. 1986;26:141–6.

    Article  CAS  PubMed  Google Scholar 

  3. Marvola M, Rajaniemi M, Marttila E, Vahervuo K, Sothmann A. Effect of dosage form and formulation factors on the adherence of drug to the esophagus. J Pharm Sci. 1983;72:1034–6.

    Article  CAS  PubMed  Google Scholar 

  4. Channer KS, Virjee JP. The effect of formulation on oesophageal transit. J Pharm Pharmacol. 1985;37:126–9.

    Article  CAS  PubMed  Google Scholar 

  5. Channer KS, Virjee JP. Effect of posture and drink volume on the swallowing of capsules. Br Med J. 1982;285:1702.

    Article  CAS  Google Scholar 

  6. Kikendall JW, Friedman AC, Oyewole MA, Fleischer D, Johnson LF. Pill-induced esophageal injury. Dig Dis Sci. 1983;28:174–82.

    Article  CAS  PubMed  Google Scholar 

  7. de Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznik MJ, Pinkas H, Wang KK. Esophagitis associated with the use of alendronate. N Engl J Med. 1996;335:1016–21.

    Article  PubMed  Google Scholar 

  8. Kluk A, Szintowska M. Application properties of oral gels as media for administration of minitablets and pellets to paediatric patients. Int J Pharm. 2014;460:228–33.

    Article  CAS  PubMed  Google Scholar 

  9. Colorcon. Modern tablet film coatings and influence on ease of swallowing. p. 1–6. Available from: http://www.colorcon.com/literature/marketing/Tabletdesign/ads_ease_of_swallowing_ver2_02_2011.pdf.

  10. Perkins AC, Wilson CG, Fried M, Blackshaw PE, Juan D, Dansereau RJ, Hathaway S, Li Z, Long P, Spiller RC. Oesophageal transit, disintegration and gastric emptying of a film-coated risendronate placebo tablet in gastro-oesophageal reflux disease and normal control subjects. Aliment Pharmacol Ther. 2001;15:115–21.

    Article  CAS  PubMed  Google Scholar 

  11. Di Maio S, Carrier RL. Gastrointestinal contents in fasted state and post-lipid ingestion: In vivo measurements and in vitro models for studying oral drug delivery. J. Contr. Rel. 2011;151:110–22.

    Article  CAS  Google Scholar 

  12. Camilleri M, Malagelada JR, Brown ML, Becker G, Zinsmeister AR. Relation between antral motility and gastric emptying of solids and liquids in humans. Am J Physiol Gastrointest Liver Physiol. 1985;249:G580–5.

    CAS  Google Scholar 

  13. Calbet JA, MacLean DA. Role of caloric content on gastric emptying in humans. J Physiol. 1997;498:553–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McLauchlan G, Fullarton GM, Crean GP, McColl KE. Comparison of gastric body and antral pH: a 24 hour ambulatory study in healthy volunteers. Gut. 1989;30:573–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Davis SS, Khosla R, Wilson CG, Washington N. Gastrointestinal transit of a controlled-release pellet formulation of tiaprofenic acid and the effect of food. Int J Pharm. 1987;35:253–8.

    Article  CAS  Google Scholar 

  16. Davis SS, Hardy JG, Taylor MJ, Whalley DR, Wilson CG. A comparative study of the gastrointestinal transit of a pellet and a tablet formulation. Int J Pharm. 1984;21:167–77.

    Article  CAS  Google Scholar 

  17. Pal A, Brasseur JG, Abrahamsson B. A stomach road or “Magenstrasse” for gastric emptying. J Biomech. 2007;40:1202–10.

    Article  PubMed  Google Scholar 

  18. Davis SS, Hardy JG, Fara JW. Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986;27:886–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Davenport HW. Physiology of the digestive tract. 4th ed. Chicago: Year Book Medical Publishers Incorporated; 1977. p. 205–15.

    Google Scholar 

  20. Augustijns P, Wuyts B, Hens B, Annaert P, Butler J, Brouwers J. A review of drug solubility in human intestinal fluids: implications for the prediction of oral absorption. Eur J Pharm Sci. 2014;57:322–32.

    Article  CAS  PubMed  Google Scholar 

  21. Yuen KH, Deshmukh AA, Newton JM, Short M, Melchor R. Gastrointestinal transit and absorption of theophylline from a multiparticulates controlled release formulation. Int J Pharm. 1993;97:61–77.

    Article  CAS  Google Scholar 

  22. Clarke GM, Newton JM, Short MD. Comparative gastrointestinal transit of pellet systems of varying density. Int J Pharm. 1995;114:1–11.

    Article  CAS  Google Scholar 

  23. Coupe AJ, Davis SS, Wilding IR. Variation in gastrointestinal transit of pharmaceutical dosage forms in healthy subjects. Pharm Res. 1991;8:360–4.

    Article  CAS  PubMed  Google Scholar 

  24. Schiller C, Fröhlich CP, Giessmann T, Siegmund W, Mönnikes H, Hosten N, Weitschies W. Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2005;22:971–9.

    Article  CAS  PubMed  Google Scholar 

  25. Wilson CG. The transit of dosage forms through the colon. Int J Pharm. 2010;395:17–25.

    Article  CAS  PubMed  Google Scholar 

  26. Zarate N, Mohammed SD, O’Shaughnessy E, Newell M, Yazaki E, Williams NS, Lunniss PS, Semler JR, Scott SM. Accurate localization of a fall in pH within the ileocecal region: validation using a dual-scintigraphic technique. Am J Physiol Gastrointest Liver Physiol. 2010;299:G1276–86.

    Article  CAS  PubMed  Google Scholar 

  27. Fallinborg J, Christensen LA, Ingeman-Nielsen M, Jacobsen BA, Abildgaard K, Rasmussen HH, Rasmussen SN. Gastrointestinal pH and transit times in healthy subjects with ileostomy. Aliment Pharmacol Ther. 1990;4:247–53.

    Article  Google Scholar 

  28. Scholtz J, Van der Colff J, Steenekamp J, Steiger N, Hamman J. More good news about polymeric plant- and algae-derived biomaterials in drug delivery systems. Curr Drug Targets. 2014;15:486–501.

    Article  CAS  PubMed  Google Scholar 

  29. Sriamornsak P. Application of pectin in oral drug delivery. Expert Opin Drug Deliv. 2011;8:1009–23.

    Article  CAS  PubMed  Google Scholar 

  30. McDougall CL, Wong R, Scudera P, Lesser M, DeCosse JJ. Colonic mucosal pH in humans. Dig Dis Sci. 1993;38:542–5.

    Article  CAS  PubMed  Google Scholar 

  31. McConnell EL, Short MD, Basit AW. An in vivo comparison of intestinal pH and bacteria as physiological trigger mechanisms for colonic targeting in man. J. Contr. Rel. 2008;130:154–60.

    Article  CAS  Google Scholar 

  32. Jain A, Gupta Y, Jain SK. Azo chemistry and its potential for colonic delivery. Crit Rev Ther Drug Carrier Syst. 2006;23:349–400.

    Article  CAS  PubMed  Google Scholar 

  33. Rao SSC, Kuo B, McCallum RW, Chey WD, DiBaise JK, Hasler WL, Koch KL, Lackner JM, Miller C, Saad R, Semler JR, Sitrin MD, Wilding GE, Parkman HP. Investigation of colonic and whole-gut transit with wireless motility capsule and radioopaque markers in constipation. Clin Gastroenterol Hepatol. 2009;7:537–44.

    Article  PubMed  Google Scholar 

  34. Krevsky B, Malmud LS, D’Ercole F, Maurer AH, Fisher RS. Colonic transit scintigraphy. A physiologic approach to the quantitative measurement of colonic transit in humans. Gastroenterology. 1986;91:1102–12.

    Article  CAS  PubMed  Google Scholar 

  35. Hajar R. Animal testing and medicine. Heart Views. 2011;12:42.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bera K, Khanam J, Mohanraj KP, Mazumder B. Design and evaluation of mucoadhesive beads of glipizide as a controlled release drug delivery system. J Microencapsul. 2014;31:220–09.

    Article  CAS  PubMed  Google Scholar 

  37. Belgamwar VS, Surana SJ. Design and development of oral mucoadhesive multiparticulates system containing atenolol: in vitro-in vivo characterization. Chem Pharm Bull (Tokyo). 2010;58:1168–75.

    Article  CAS  Google Scholar 

  38. Jain SK, Jangdey MS. Lectin conjugated gastroretentive multiparticulates delivery system of clarithromycin for the effective treatment of helicobacter pylori. Mol Pharm. 2009;6:295–304.

    Article  CAS  PubMed  Google Scholar 

  39. Brunner M, Greinwald R, Kletter K, Kvaternik H, Corrado ME, Eichler HG, Müller M. Gastrointestinal transit and release of 5-aminosalicylic acid from 153Sm-labelled mesalazine pellets vs. tablets in male healthy volunteers. Aliment Pharmacol Ther. 2003;17:1163–9.

    Article  CAS  PubMed  Google Scholar 

  40. Hardy JG, Lamont GL, Evans DF, Haga AK, Gamst ON. Evaluation of an enteric-coated naproxed pellet formulation. Aliment Pharmacol Ther. 1991;5:69–75.

    Article  CAS  PubMed  Google Scholar 

  41. Hardy JG, Harvey WJ, Sparrow RA, Marshall GB, Steed KP, Macarios M, Wilding IR. Localization of drug release sites from an oral sustained-release formulation of 5-ASA (Pentasa) in the gastrointestinal tract using gamma scintigraphy. J Clin Pharmacol. 1993;33:712–8.

    Article  CAS  PubMed  Google Scholar 

  42. Wilding IR, Behrens C, Tardif SJ, Wray H, Bias P, Albrecht W. Combined scintigraphic and pharmacokinetic investigation of enteric-coated mesalazine micropellets in healthy subjects. Aliment Pharmacol Ther. 2003;17:1153–62.

    Article  CAS  PubMed  Google Scholar 

  43. Devereux JE, Newton JM, Short MB. The influence of density on the gastrointestinal transit of pellets. J Pharm Pharmacol. 1990;42:500–1.

    Article  CAS  PubMed  Google Scholar 

  44. Digenis GA, Sandefer EP, Parr AF, Beihn R, McClain C, Scheinthal BM, Ghebre-Sellassie I, Iyer U, Nesbitt RU, Randinitis E. Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy. J Clin Pharmacol. 2013;30:621–31.

    Article  Google Scholar 

  45. Iwanaga Y, Wen J, Thollander MS, Kost LJ, Thomforde GM, Allen RG, Phillips SF. Scintigraphic measurement of regional gastrointestinal transit in the dog. Am J Phys. 1998;275:G904–10.

    CAS  Google Scholar 

  46. McInnes F, Clear N, Humphrey M, Stevens HN. In vivo performance of an oral MR matrix tablet formulation in the beagle dog in the fed and fasted state: assessment of mechanical weakness. Pharm Res. 2008;25:1075–84.

    Article  CAS  PubMed  Google Scholar 

  47. Davis J, Burton J, Connor AL, Macrae R, Wilding IR. Scintigraphic study to investigate the effect of food on a HPMC modified release formulation of UK-294,315. J Pharm Sci. 2009;98:1568–76.

    Article  CAS  PubMed  Google Scholar 

  48. Moore JG, Datz FL, Christian PE, Greenberg E, Alazraki N. Effect of body posture on radionuclide measurements of gastric emptying. Dig Dis Sci. 1998;33:1592–5.

    Article  Google Scholar 

  49. Weitschies W, Blume H, Mönnikes H. Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract. Eur J Pharm Biopharm. 2010;74:93–101.

    Article  CAS  PubMed  Google Scholar 

  50. Weitschies W, Kosch O, Mönnikes H, Trahms L. Magnetic marker monitoring: an application of biomagnetic measurement instrumentation and principles for the determination of the gastrointestinal behavior of magnetically marked solid dosage forms. Adv Drug Deliv Rev. 2005;57:1210–22.

    Article  CAS  PubMed  Google Scholar 

  51. Bork J, Hahlbohm HD, Klein R, Schnabel A. The 8-layered magnetically shielded room of the PTB: Design and construction. In: Nenonen J, Ilmoniemi RJ, Katila T, editors. Biomag 2000, Proc. 12th Int. Conf. On Biomagnetism. Espoo: Helsinki Univ. of Technology. p. 970–3.

    Google Scholar 

  52. Mehta S, Verstraelen H, Peremans K, Villeirs G, Vermeire S, De Vos F, Mehuys E, Remon JP, Vervaet C. Vaginal distribution and retention of a multiparticulates drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging. Int J Pharm. 2012;426:44–53.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang C, Xu M, Tao X, Tang J, Liu Z, Zhang Y, Lin X, He H, Tang X. A floating multiparticulate system for ofloxacin based on a multilayer structure: in vitro and in vivo evaluation. Int J Pharm. 2012;430:141–50.

    Article  CAS  PubMed  Google Scholar 

  54. van der Schaar PJ, Dijksman JF, Broekhuizen-de Gast H, Shimizu J, van Lelyveld N, Zou H, Iordanov V, Wanke C, Siersema PD. A novel ingestible electronic drug delivery and monitoring device. Gastrointest Endosc. 2013;78:520–8.

    Article  PubMed  Google Scholar 

  55. Koziolek M, Grimm M, Becker D, Iordanov V, Zou H, Shimizu J, Wanke C, Garbacz G, Weitschies W. Investigation of pH and temperature profiles in the GI tract of fasted human subjects using the IntelliCap® system. J Pharm Sci. 2014; doi:10.1002/jps.24274. [Epub ahead of print]

    PubMed  Google Scholar 

  56. Amrutkar PP, Chaudhari PD, Patil SB. Design and in vitro evaluation of multiparticulates floating drug delivery system of zolpidem tartrate. Colloids Surf B Biointerfaces. 2012;89:182–7.

    Article  CAS  PubMed  Google Scholar 

  57. Whitehead L, Fell JT, Collett JH, Sharma HL, Smith A-M. Floating dosage forms: an in vivo study demonstrating prolonged gastric retention. J Contr Rel. 1998;55:3–12.

    Article  CAS  Google Scholar 

  58. Whitehead L, Collett JH, Fell JT. Amoxycillin release from a floating dosage form based on alginates. Int J Pharm. 2000;210:45–9.

    Article  CAS  PubMed  Google Scholar 

  59. Murata Y, Sasaki N, Miyamoto E, Kawashima S. Use of floating alginate gel beads for stomach-specific drug delivery. Eur J Pharm Biopharm. 2000;50:221–6.

    Article  CAS  PubMed  Google Scholar 

  60. Ichikawa M, Watanabe S, Miyake Y. Granule remaining in stomach. EP 0 235 718, 9 September. 1987.

    Google Scholar 

  61. Krögel I, Bodmeier R. Floating or pulsatile drug delivery systems based on coated effervescent cores. Int J Pharm. 1999;187:175–84.

    Article  PubMed  Google Scholar 

  62. Zhao L, Xu H, Li S, Li Q, Zhang W, Ye T, Yang X, Pan W. A novel gastro-floating multiparticulate system for dipyridamole (DIP) based on a porous and low-density matrix core: in vitro and in vivo evaluation. Int J Pharm. 2014;461:540–8.

    Article  Google Scholar 

  63. Brunner M, Lackner E, Exler PS, Fluiter HC, Kletter K, Tschurlovits M, Dudczak R, Eichler HG, Müller M. 5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteers. Aliment Pharmacol Ther. 2006;23:137–44.

    Article  CAS  PubMed  Google Scholar 

  64. Sandborn WJ, Hanauer SB. Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis. Aliment Pharmacol Ther. 2003;17:29–42.

    Article  CAS  PubMed  Google Scholar 

  65. D’Incà R, Paccagnella M, Cardin R, Pathak S, Baldo V, Giron MC, Sturniolo GC. 5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis. World J Gastroenterol. 2013;19:5665–70.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Angelberger S, Schaeffeler E, Teml A, Petritsch W, Shonova O, Lukas M, Bar-Meir S, Dilger K, Greinwald R, Mueller R, Stange EF, Herrlinger KR, Schwab M, Reinisch W. Mucosal improvement in patients with moderate to severe postoperative endoscopic recurrence of Crohn’s disease and azathioprine metabolite levels. Inflamm Bowel Dis. 2013;19:590–8.

    Article  PubMed  Google Scholar 

  67. Bautzová T, Rabišková M, Béduneau A, Pellequer Y, Lamprecht A. Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis. Eur J Pharm Biopharm. 2012;81:379–85. Majumdar S, Roy S, Ghosh B. Design and gamma scintigraphic evaluation of colon specific pectin-EC pellets of secnidazole prepared by powder layering technology. Pharmazie. 2011;66:843–8.

    Article  PubMed  Google Scholar 

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  1. Quintiles Malaysia Sdn Bhd, Suite D-08-02, Plaza Mont Kiara, No 2, Jalan Kiara, Mont Kiara, 50480, Kuala Lumpur, Malaysia

    Lee Ann Hodges MPharm (Hons), PhD

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  1. Lee Ann Hodges MPharm (Hons), PhD
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Correspondence to Lee Ann Hodges MPharm (Hons), PhD .

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  1. VP & Chief Scientific Officer, Colorcon Inc., Harleysville, Pennsylvania, USA

    Ali R. Rajabi-Siahboomi

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Hodges, L.A. (2017). In Vivo Characterization of Oral Multiparticulate Systems. In: Rajabi-Siahboomi, A. (eds) Multiparticulate Drug Delivery. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7012-4_14

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