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AAPS PharmSciTech

, Volume 13, Issue 1, pp 1–15 | Cite as

Optimization of a Dual Mechanism Gastrofloatable and Gastroadhesive Delivery System for Narrow Absorption Window Drugs

  • Caragh Murphy
  • Viness Pillay
  • Yahya E. Choonara
  • Lisa C. du Toit
  • Valence M. K. Ndesendo
  • Nthato Chirwa
  • Pradeep Kumar
Research Article Theme: Advanced Technologies for Oral Controlled Release

Abstract

In order to overcome poor bioavailability of narrow absorption window drugs, a gastrosphere system comprising two mechanisms of gastric retention, namely buoyancy and gastroadhesion, has been investigated in this study employing poly(lactic-co-glycolic acid) (PLGA), polyacrylic acid (PAA), alginate, pectin, and a model drug metformin hydrochloride. Fifteen formulations were obtained using a Box–Behnken statistical design. The gastrosphere yield was above 80% in all cases; however, due to the high water solubility of metformin, drug entrapment efficacy was between 18% and 54%. Mean dissolution time and gastroadhesive strength were used as the formulation responses in order to optimize the formulation. Furthermore, the molecular mechanics force field simulations were performed to corroborate the experimental findings. Drug release profiles revealed three different release kinetics, namely, burst, first-order and zero-order release. Varying gastroadhesive results were obtained, and were highly sensitive to changes in polymer concentrations. FTIR revealed that strong bonds of PAA and PLGA were retained within the gastrosphere. Surface area and porosity analysis provided supporting evidence that the lyophilization process resulted in a significant increase in the porosity. Analysis of the surface morphology by SEM revealed that air pockets were spread over the entire surface of the gastrosphere, providing a visual proof of the high porosity and hence low density of the gastrosphere. The spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex of alginate, pectin, PAA, and PLGA corroborated the experimental results in terms of in vitro drug release and gastroadhesive strength of the fabricated gastrospheres.

KEY WORDS

Box–Behnken design gastroretentive drug delivery molecular mechanics simulations narrow absorption window drugs polymeric gastrosphere synthesis 

REFERENCES

  1. 1.
    Chung HJ, Park TG. Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering. Adv Drug Delivery Rev. 2007;59:249–62.CrossRefGoogle Scholar
  2. 2.
    Biondi M, Ungaro F, Quaglia F, Netti PA. Controlled drug delivery in tissue engineering. Adv Drug Delivery Rev. 2008;60:229–42.CrossRefGoogle Scholar
  3. 3.
    Sam MT, Gayathri DS, Prasanth V, Vinod B. NSAIDs as microspheres. Internet J Pharmacol. 2008;6(1):1–8.Google Scholar
  4. 4.
    Gilhotra RM, Mishra DN. Polymeric systems for ocular inserts. In: Latest Reviews. 2009. Pharmainfo.net: Pharmaceutical information for you. http://www.pharmainfo.net/reviews/polymeric-systems-ocular-inserts [accssed May 30, 2010].
  5. 5.
    Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric systems for controlled drug release. Chem Rev. 1999;99(11):3181–98.PubMedCrossRefGoogle Scholar
  6. 6.
    Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable gastroretentive dosage forms. J Control Release. 2003;90(2):143–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Kim S, Kim JH, Jeon O, Kwon IC, Park K. Engineered polymers for advanced drug delivery. Eur J Pharm Biopharm. 2009;71(3):420–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Davis SS. Formulation strategies for absorption windows. Drug Deliv Today. 2005;10(4):249–57.CrossRefGoogle Scholar
  9. 9.
    Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E, Friedman M. Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms. Int J Pharm. 2004;277(1–2):141–53.PubMedCrossRefGoogle Scholar
  10. 10.
    Tang YD, Venkatraman SS, Boey FYC, Wang LW. Sustained release of hydrophobic and hydrophilic drugs from a floating dosage form. Int J Pharm. 2007;336(11):159–65.PubMedCrossRefGoogle Scholar
  11. 11.
    Singh BS, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Control Release. 2000;63(3):235–59.PubMedCrossRefGoogle Scholar
  12. 12.
    Streubel A, Siepmann J, Bodmeier R. Drug delivery to the upper small intestine window using gastroretentive technologies. Curr Opin Pharmacol. 2006;6:501–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Chavanpatil MD, Jain P, Chaudhari S, Shear R, Vavia PR. Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for olfloxacin. Int J Pharm. 2006;316(1–2):86–92.PubMedCrossRefGoogle Scholar
  14. 14.
    El-Gibaly I. Development and in vitro evaluation of novel floating chitosan microcapsules for oral use: comparison with non-floating chitosan microspheres. Int J Pharm. 2002;249(1–2):7–21.PubMedCrossRefGoogle Scholar
  15. 15.
    Fukuda M, Peppas NA, McGinity JW. Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J Control Release. 2006;115(2):121–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Ahmed IS, Ayres JW. Bioavailability of riboflavin from a gastric retentive formulation. Int J Pharm. 2007;330(1–2):146–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl-b-cyclodextrin. Eur J Pharm Biopharm. 2008;68(2):303–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Porta V, Schramm SG, Kano EK, Koono EE, Armando YP, Fukuda K, et al. HPLC-UV determination of metformin in human plasma for application in pharmacokinetics and bioequivalence studies. J Pharm Biomed Anal. 2008;46(1):143–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Gibbon CJ, Blockman M. South African Medicines Formulary (SAMF). 8th ed. Cape Town: Health and Medical Publishing Group of the South African Medical Association; 2007.Google Scholar
  20. 20.
    Stops F, Fell JT, Collett JH, Martini LG, Sharma HL, Smith AM. The use of citric acid to prolong the in vivo gastro-retention of a floating dosage form in the fasted state. Int J Pharm. 2006;308(1–2):8–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Streubel A, Siepmann J, Bodmeier R. Floating microparticles based on low density foam powder. Int J Pharm. 2002;241(2):279–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Tu J, Bolla S, Barr J, Meidema J, Li X, Jasti B. Alginate microparticles prepared by spray-coagulation method: preparation, drug loading and release characteristics. Int J Pharm. 2005;303(1–2):171–81.PubMedCrossRefGoogle Scholar
  23. 23.
    Xu Y, Zhan C, Fan L, Wang L, Zheng H. Preparation dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int J Pharm. 2007;336(2):329–37.PubMedCrossRefGoogle Scholar
  24. 24.
    Al-Kassas RS, Al-Gohary OMN, Al-Faadhel MM. Controlling of systemic absorption of gliclazide through incorporation into alginate beads. Int J Pharm. 2007;342(1–2):230–7.CrossRefGoogle Scholar
  25. 25.
    Itoh K, Hirayama T, Takahashi A, Kubo W, Miyazaki S, Dairaku M, et al. In situ gelling pectin formulations for oral drug delivery at high gastric pH. Int J Pharm. 2007;335(1–2):90–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Wei X, Sun N, Wu B, Yin C, Wu W. Sigmoidal release of indomethacin from pectin matrix tablets: Effect of in situ crosslinking by calcium cations. Int J Pharm. 2006;318(1–2):132–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Khutoryanskiy VV. Hydrogen-bonded interpolymer complexes as materials for pharmaceutical applications. Int J Pharm. 2007;334(1–2):15–26.PubMedCrossRefGoogle Scholar
  28. 28.
    Jin L, Lu P, You H, Chen Q, Dong J. Vitamin B12 diffusion and binding in crosslinked poly(acrylic acid)s and poly(acrylic acid-co-N-vinyl pyrrolidinone)s. Int J Pharm. 2009;371(1–2):82–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Mok H, Park TG. Water-free microencapsulation of proteins within PLGA microparticles by spray drying using PEG-assisted protein solubilisation technique in organic solvent. Eur J Pharm Biopharm. 2008;70(1):137–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Klose D, Siepmann F, Willart JF, Descamps M, Siepmann J. Drug release from PLGA-based microparticles: effects of the “microparticle:bulk fluid” ratio. Int J Pharm. 2010;383(1–2):123–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Pillay V, Fassihi R. In vitro release modulation from crosslinked pellets for site-specific drug delivery to the gastrointestinal tract: comparison of pH-responsive drug release and associated kinetics. J Control Release. 1999;59(2):229–42.PubMedCrossRefGoogle Scholar
  32. 32.
    Hopfenberg HB, Hsu KC. Swelling-controlled constant rate delivery systems. Polym Eng Sci. 1978;18(15):1186–91.CrossRefGoogle Scholar
  33. 33.
    da Silva MA, Bierhalz ACK, Kieckbusch TG. Alginate and pectin composite films crosslinked with Ca2+ ions: effect of the plasticizer concentration. Carbohyd Polym. 2009;77:736–42.CrossRefGoogle Scholar
  34. 34.
    Kriwet B, Kissel T. Interactions between bioadhesive poly(acrylic acid) and calcium ions. Int J Pharm. 1996;127(2):135–45.CrossRefGoogle Scholar
  35. 35.
    Braccini I, Pérez S. Molecular basis of Ca2+-induced gelation in alginates and pectins: the egg-box model revisited. Biomacromolecules. 2001;2:1089–96.PubMedCrossRefGoogle Scholar
  36. 36.
    Kumar P, Bhatia M. Functionalization of chitosan/methylcellulose interpenetrating polymer network microspheres for gastroretentive application using central composite design. PDA J Pharm Sci Technol. 2010;64(6):497–506.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Caragh Murphy
    • 1
  • Viness Pillay
    • 1
  • Yahya E. Choonara
    • 1
  • Lisa C. du Toit
    • 1
  • Valence M. K. Ndesendo
    • 1
  • Nthato Chirwa
    • 1
  • Pradeep Kumar
    • 1
  1. 1.University of the Witwatersrand, Faculty of Health SciencesDepartment of Pharmacy and PharmacologyJohannesburgSouth Africa

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