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Mechanistic Approach to Understanding the Influence of USP Apparatus I and II on Dissolution Kinetics of Tablets with Different Operating Release Mechanisms

AAPS PharmSciTech volume 18, pages 462–472 (2017)Cite this article

Abstract

This article provides an analysis of dissolution kinetics associated with formulations subjected to different dissolution methods with the purpose of revealing credible direction on selection of apparatus type and hydrodynamics on in vitro drug release profiles using three different formulations. The dissolution kinetics of immediate release (IR) and controlled release (CR) ibuprofen tablets under different hydrodynamic conditions were determined, and potential existence of any correlation between USP apparatus I and II were analyzed using adequate kinetic models. Two types of CR tablets based on PEO (polyethylene oxide-N80) and HPMC (hydroxypropyl methylcellulose- K100M) polymers were prepared. Marketed ibuprofen 200-mg IR tablets were also used. Dissolution studies were carried out using USP 34 apparatuses I and II methods at stirring speed of 100 and 50 rpm in 900 mL phosphate buffer, pH 7.2 at 37°C. The drug release profiles for each formulation was determined and statistically analyzed using model-dependent, model-independent (f 2 ), and ANOVA methods. No significant dissolution differences existed between IR tablets, whereas CR tablets were significantly impacted by apparatus types and hydrodynamics. PEO matrices displayed higher sensitivity to hydrodynamics relative to HPMC matrices, and differences in dissolution profiles were confirmed by ANOVA and boxplot analysis. It is concluded that in the case of CR systems, selection of apparatus type and adherence to the monograph specifications and hydrodynamic conditions is critical, while for IR tablets, both apparatus types and agitation rates had no significant impact on drug release rate, suggesting the possibility of apparatus interchangeability if desired.

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REFERENCES

  1. Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 1897;19:930–4.

    Article  Google Scholar 

  2. Brunner E. Reaktionsgeschwindigkeit in heterogenen Systemen. Z Phys Chem. 1904;43:56–102.

    Google Scholar 

  3. Nernst W. Theorie der Reaktionsgeschwindigkeit in heterogenen Systemen. Z Phys Chem. 1904;47:52–5.

    CAS  Google Scholar 

  4. Macheras P, Dokoumetzidis A. On the heterogeneity of drug dissolution and release. Pharm Res. 2000;17(2):108–12.

    CAS  Article  PubMed  Google Scholar 

  5. Weibull W. A statistical distribution function of wide applicability. J Appl Mech. 1951;18:293–7.

    Google Scholar 

  6. Langenbucher F. Linearization of dissolution rate curves by the Weibull distribution. J Pharm Pharmacol. 1972;24:979–81.

    CAS  Article  PubMed  Google Scholar 

  7. Costa P, Lobo JS. Influence of dissolution medium agitation on release profiles of sustained-release tablets. Drug Dev Ind Pharm. 2001;27(8):811–7.

    CAS  Article  Google Scholar 

  8. Missaghi S, Fassihi R. Release characterization of dimenhydrinate from an eroding and swelling matrix: selection of appropriate dissolution apparatus. Int J Pharm. 2005;293(1):35–42.

    CAS  Article  PubMed  Google Scholar 

  9. Pillay V, Fassihi R. Unconventional dissolution methodologies. J Pharm Sci. 1999;88(9):843–51.

    CAS  Article  PubMed  Google Scholar 

  10. Underwood FL, Cadwallader DE. Effects of various hydrodynamic conditions on dissolution rate determinations. J Pharm Sci. 1976;65(5):697–700.

    CAS  Article  PubMed  Google Scholar 

  11. Shah VP, Gurbarg M, Noory A, Dighe S, Skelly JP. Influence of higher rates of agitation on release patterns of immediate-release drug products. J Pharm Sci. 1992;81(6):500–3.

    CAS  Article  PubMed  Google Scholar 

  12. Jamzad S, Fassihi R. Role of surfactant and pH on dissolution properties of fenofibrate and glipizide—a technical note. AAPS PharmScitech. 2006;7(2):E17–22.

    Article  PubMed Central  Google Scholar 

  13. Pillay V, Fassihi R. A new method for dissolution studies of lipid-filled capsules employing nifedipine as a model drug. Pharm Res. 1999;16(2):333–7.

    CAS  Article  PubMed  Google Scholar 

  14. Mirza T, Joshi Y, Liu Q, Vivilecchia R. Evaluation of dissolution hydrodynamics in the USP, Peak™ and flat-bottom vessels using different solubility drugs. Dissolution Technol. 2005;12(1):11–6.

    CAS  Article  Google Scholar 

  15. Röst M, Quist PO. Dissolution of USP prednisone calibrator tablets: effects of stirring conditions and particle size distribution. J Pharm Biomed Anal. 2003;31(6):1129–43.

    Article  PubMed  Google Scholar 

  16. Wurster DE, Taylor PW. Dissolution rates. J Pharm Sci. 1965;54(2):169–75.

    CAS  Article  PubMed  Google Scholar 

  17. Levy G. Effect of particle size on dissolution and gastrointestinal absorption rates of pharmaceuticals. Am J Pharm Sci Support Public Health. 1963;135:78–92.

    CAS  PubMed  Google Scholar 

  18. Shaw LR, Irwin WJ, Grattan TJ, Conway BR. The effect of selected water-soluble excipients on the dissolution of paracetamol and ibuprofen. Drug Dev Ind Pharm. 2005;31(6):515–25.

    CAS  Article  PubMed  Google Scholar 

  19. Yuksel N, Kanık AE, Baykara T. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and-independent methods. Int J Pharm. 2000;209(1):57–67.

    CAS  Article  PubMed  Google Scholar 

  20. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–1.

    CAS  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  22. Varelas CG, Dixon DG, Steiner C. Zero-order release from biphasic polymer hydrogels. J Control Release. 1995;34:185–92.

    CAS  Article  Google Scholar 

  23. Mulye NV, Turco SJ. A simple model based on first order kinetics to explain release of highly water soluble drugs from porous dicalcium phosphate dihydrate matrices. Drug Dev Ind Pharm. 1995;21:943–53.

    CAS  Article  Google Scholar 

  24. Baker RW, Lonsdale HS. Controlled release: mechanisms and rates. In: Taquary AC, Lacey RE, editors. Controlled release of biologically active agents. New York: Plenum Press; 1974. p. 15–71.

    Chapter  Google Scholar 

  25. Hixson AW, Crowell JH. Dependence of reaction velocity upon surface and agitation. Ind Eng Chem. 1931;23:923–31.

    CAS  Article  Google Scholar 

  26. Goldsmith JA, Randall N, Ross SD. On methods of expressing dissolution rate data. J Pharm Pharmacol. 1978;30:347–9.

    CAS  Article  PubMed  Google Scholar 

  27. Hanson W. Handbook of dissolution testing. 2nd ed. Eugene Oregon: Aster Publishing Corporation; 1991. p. 35.

    Google Scholar 

  28. Guidance for Industry: Immediate Release Solid Oral Dosage Forms Scale-up and Postapproval Changes: Chemistry, Manufacturing, and Controls. In Vitro Dissolution Testing and in Vivo Bioequivalence Documentation. Center for Drug Evaluation and Research (CDER), CMC 5. 1995. http://www.fda.gov/downloads/Drugs/…/Guidances/UCM070636.pdf. Accessed Nov 1995.

  29. Gonçalves-Araújo T, Rajabi-Siahboomi AR, Caraballo I. Polymer percolation threshold in HPMC extended release formulation of carbamazepine and verapamil HCl. AAPS PharmSciTech. 2010;11(2):558–62.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Berens AR, Hopfenberg HB. Diffusion and relaxation in glassy polymer powders: 2. Separation of diffusion and relaxation parameters. Polymer. 1978;19(5):489–96.

    CAS  Article  Google Scholar 

  31. Dürig T, Fassihi R. Guar-based monolithic matrix systems: effect of ionizable and non-ionizable substances and excipients on gel dynamics and release kinetics. J Control Release. 2002;80(1):45–56.

    Article  PubMed  Google Scholar 

  32. Peppas NA, Sahlin JJ. A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int J Pharm. 1989;57(2):169–72.

    CAS  Article  Google Scholar 

  33. Pham AT, Lee PI. Probing the mechanisms of drug release from hydroxypropylmethyl cellulose matrices. Pharm Res. 1994;11(10):1379–84.

    CAS  Article  PubMed  Google Scholar 

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

    CAS  Article  PubMed  Google Scholar 

  35. USP, General Chapter “ < 711 > Dissolution” USP 34-NF 29. Rockville: The United States Pharmacopeial Convention, 2011. p. 278–284.

  36. USP, General Chapter “ < 724 > Drug release” USP 34-NF 29. Rockville: The United States Pharmacopeial Convention, 2011. p. 285–289.

  37. USP, General Chapter “ < 1088 > In vitro and in vivo evaluation of dosage forms” USP 34-NF 29. Rockville: The United States Pharmacopeial Convention, 2011. p. 612–617.

  38. USP, General Chapter “ < 1225 > Validation of compendial procedures” USP 34-NF 29. Rockville: The United States Pharmacopeial Convention, 2011. p. 778–782.

  39. Guidance for Industry: Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 2015. http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070246.pdf. Accessed May 2015.

  40. Note for guidance on the investigation of bioavailability and bioequivalence. Committee for Proprietary Medicinal Products (CPMP). 2000. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003519.pdf. Accessed 14 Dec 2000.

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  1. School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, Pennsylvania, 19140, USA

    Zheng Lu & Reza Fassihi

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  1. Zheng Lu
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  2. Reza Fassihi
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Correspondence to Reza Fassihi.

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Lu, Z., Fassihi, R. Mechanistic Approach to Understanding the Influence of USP Apparatus I and II on Dissolution Kinetics of Tablets with Different Operating Release Mechanisms. AAPS PharmSciTech 18, 462–472 (2017). https://doi.org/10.1208/s12249-016-0535-x

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  • DOI: https://doi.org/10.1208/s12249-016-0535-x

KEY WORDS

  • controlled release matrix tablet
  • hydrodynamics
  • immediate release tablet
  • release kinetic models
  • USP apparatus I and II