AAPS PharmSciTech

, Volume 14, Issue 2, pp 605–619 | Cite as

Design of an Interpolyelectrolyte Gastroretentive Matrix for the Site-Specific Zero-Order Delivery of Levodopa in Parkinson’s Disease

  • Ndidi C. Ngwuluka
  • Yahya E. Choonara
  • Girish Modi
  • Lisa C. du Toit
  • Pradeep Kumar
  • Valence M. K. Ndesendo
  • Viness Pillay
Research Article

Abstract

This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson’s disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34–39 N/mm) and matrix resilience (44–47%) when different normality’s of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm3 and swellability values of 177–234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery.

Key words

gastroretention interpolyelectrolyte complex levodopa narrow absorption window drugs Parkinson’s disease 

REFERENCES

  1. 1.
    Birkmayer W, Hornykiewicz O. Der l-3,4-dioxyphenylalanin (=DOPA)-Effekt bei Parkinson-Akinese. Wien Klin Wochenschr. 1961;73:787–8.PubMedGoogle Scholar
  2. 2.
    Muzzi C, Bertocci E, Terzuoli L, Porcelli B, Ciari I, Pagani R, et al. Simultaneous determination of serum concentrations of levodopa, dopamine, 3-O-methyldopa and α-methyldopa by HPLC. Biomed Pharmacother. 2008;62:253–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Jankovic J. Levodopa strengths and weaknesses. Neurology. 2002;58:S19–32.CrossRefPubMedGoogle Scholar
  4. 4.
    Sagar KA, Smyth MR. Bioavailability studies of oral dosage forms containing levodopa and carbidopa using column-switching chromatography followed by electrochemical detection. Analyst. 2000;125:439–45.CrossRefPubMedGoogle Scholar
  5. 5.
    Koller WC, Hutton JT, Tolosa E, Capilldeo R. Immediate-release and controlled-release carbidopa/levodopa in PD: a 5-year randomized multicenter study. Neurology. 1999;53:1012.CrossRefPubMedGoogle Scholar
  6. 6.
    Ngwuluka N, Pillay V, Du Toit LC, Ndesendo V, Choonara Y, Modi G, et al. Levodopa delivery systems: advancements in delivery of the gold standard. Expert Opin Drug Deliv. 2010;7:203–24.CrossRefPubMedGoogle Scholar
  7. 7.
    Arza R, Gonugunta C, Veerareddy P. Formulation and evaluation of swellable and floating gastroretentive ciprofloxacin hydrochloride tablets. AAPS PharmSciTech. 2009;10:220–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Klausner EA, Eyal S, Lavy E, Friedman M, Hoffman A. Novel levodopa gastroretentive dosage form: in-vivo evaluation in dogs. J Control Release. 2003;88:117–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Goole J, Vanderbist F, Amighi K. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms. Int J Pharm. 2007;334:35–41.CrossRefPubMedGoogle Scholar
  10. 10.
    Goole J, Deleuze P, Vanderbist F, Amighi K. New levodopa sustained-release floating minitablets coated with insoluble acrylic polymer. Eur J Pharm Biopharm. 2008;68:310–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Kumar P, Pillay V, Choonara YE, Modi G, Naidoo D, du Toit LC. In Silico theoretical molecular modeling for Alzheimer’s disease: the nicotine-curcumin paradigm in neuroprotection and neurotherapy. Int J Mol Sci. 2011;12:694–724.CrossRefPubMedGoogle Scholar
  12. 12.
    Camacho MM, Martínez-Navarrete N, Chiralt A. Rheological characterization of experimental dairy creams formulated with locust bean gum (LBG) and λ-carrageenan combinations. Int Dairy J. 2005;15:243–8.CrossRefGoogle Scholar
  13. 13.
    Sittikijyothin W, Torres D, Gonçalves MP. Modelling the rheological behaviour of galactomannan aqueous solutions. Carbohydr Polym. 2005;59:339–50.CrossRefGoogle Scholar
  14. 14.
    Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive dosage forms: overview and special case of Helicobacter pylori. J Control Release. 2006;111:1–18.CrossRefPubMedGoogle Scholar
  15. 15.
    Chawla G, Gupta P, Koradia V, Bansal AK. Gastroretention: a means to address regional variability in intestinal drug absorption. Pharm Technol. 2003;27:50–68.Google Scholar
  16. 16.
    Davis SS, Hardy JG, Fara JW. Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986;27:886–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Nur A, Zhang J. Captopril floating and/or bioadhesive tablets: design and release kinetics. Drug Dev Ind Pharm. 2000;26:965.CrossRefPubMedGoogle Scholar
  18. 18.
    Lee JW, Park JH, Robinson JR. Bioadhesive-based dosage forms: the next generation. J Pharm Sci. 2000;89:850–66.CrossRefPubMedGoogle Scholar
  19. 19.
    Thirawong N, Kennedy RA, Sriamornsak P. Viscometric study of pectin–mucin interaction and its mucoadhesive bond strength. Carbohydr Polym. 2008;71:170–9.CrossRefGoogle Scholar
  20. 20.
    Vasir JK, Tambwekar K, Garg S. Bioadhesive microspheres as a controlled drug delivery system. Int J Pharm. 2003;255:13–32.CrossRefPubMedGoogle Scholar
  21. 21.
    O’Brien S, Wang Y, Vervaet C, Remon JP. Starch phosphates prepared by reactive extrusion as a sustained release agent. Carbohydr Polym. 2009;76:557–66.CrossRefGoogle Scholar
  22. 22.
    Kim SW, Bae YH, Okano T. Hydrogels: swelling, drug loading, and release. Pharm Res. 1992;9:283–90.CrossRefPubMedGoogle Scholar
  23. 23.
    Wise DL, Trantolo DJ, Altobelli DE, Yaszemski MJ, Gresser JD, Schwartz ER. Encyclopedic handbook of biomaterials and bioengineering. 1st ed. Sheffield: Marcel Dekker; 1995. p. 3760.Google Scholar
  24. 24.
    Siepmann J, Göpferich A. Mathematical modeling of bioerodible, polymeric drug delivery systems. Adv Drug Deliv Rev. 2001;48:229–47.CrossRefPubMedGoogle Scholar
  25. 25.
    Faisant N, Siepmann J, Benoit JP. PLGA-based microparticles: elucidation of mechanisms and a new, simple mathematical model quantifying drug release. Eur J Pharm Sci. 2002;15:355–66.CrossRefPubMedGoogle Scholar
  26. 26.
    Merchant H, Shoaib H, Tazeen J, Yousuf R. Once-daily tablet formulation and in vitro release evaluation of cefpodoxime using hydroxypropyl methylcellulose: a technical note. AAPS PharmSciTech. 2006;7:E178–83.CrossRefGoogle Scholar
  27. 27.
    Sriamornsak P, Thirawong N, Weerapol Y, Nunthanid J, Sungthongjeen S. Swelling and erosion of pectin matrix tablets and their impact on drug release behavior. Eur J Pharm Biopharm. 2007;67:211–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Greaves JL, Wilson CG. Treatment of diseases of the eye with mucoadhesive delivery systems. Adv Drug Deliv Rev. 1993;11:349–83.CrossRefGoogle Scholar
  29. 29.
    Jelinek M, Cristescu R, Axente E, Kocourek T, Dybal J, Remsa J, et al. Matrix assisted pulsed laser evaporation of cinnamate-pullulan and tosylate-pullulan polysaccharide derivative thin films for pharmaceutical applications. Appl Surf Sci. 2007;253:7755–60.CrossRefGoogle Scholar
  30. 30.
    Abou-Rachid H, Lussier L, Ringuette S, Lafleur-Lambert X, Jaidann M, Brisson J. On the correlation between miscibility and solubility properties of energetic plasticizers/polymer blends: modeling and simulation studies. Propell Explos Pyrot. 2008;33:301–10.CrossRefGoogle Scholar
  31. 31.
    Murphy C, Pillay V, Choonara Y, du Toit L, Ndesendo V, Chirwa N, et al. Optimization of a dual mechanism gastrofloatable and gastroadhesive delivery system for narrow absorption window drugs. AAPS PharmSciTech. 2012;13(1):1–15.CrossRefPubMedGoogle Scholar
  32. 32.
    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;64:497–506.PubMedGoogle Scholar
  33. 33.
    Kumar P, Singh I. Formulation and characterization of tramadol-loaded IPN microgels of alginate and gelatin: optimization using response surface methodology. Acta Pharm. 2010;60:295–310.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Ndidi C. Ngwuluka
    • 1
  • Yahya E. Choonara
    • 1
  • Girish Modi
    • 2
  • Lisa C. du Toit
    • 1
  • Pradeep Kumar
    • 1
  • Valence M. K. Ndesendo
    • 3
  • Viness Pillay
    • 1
  1. 1.Department of Pharmacy and Pharmacology, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  2. 2.Department of Neurology, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
  3. 3.School of Pharmacy and Pharmaceutical SciencesSt. John’s University of TanzaniaDodomaTanzania

Personalised recommendations