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Understanding Biorelevant Drug Release from a Novel Thermoplastic Capsule by Considering Microstructural Formulation Changes During Hydration

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Abstract

Purpose

To study the biorelevant drug release from novel starch-based polyvinyl alcohol capsules (S-PVA-C). The effect of the shell material is studied by considering microstructural formulation changes during hydration.

Methods

Two different self-emulsifying systems containing either fenofibrate or probucol were filled in S-PVA-C, as well as capsules of gelatin (SGC) and starch (VegaGels®). Release analysis employed a BioDis® apparatus, while disintegration was studied by texture analysis. For microstructural analysis we used small angle x-ray scattering (SAXS).

Results

S-PVA-C opened only partially in biorelevant media compared to completely opened SGC and VegaGels®. In case of the fenofibrate formulation, this opening mechanism caused only a short lag time, while the probucol formulation in S-PVA-C resulted in a sustained release. The latter formulation demonstrated much higher viscosity upon hydration compared to the fenofibrate system. Such a rheological effect on drug release was barely noted for SGC or VegaGels® and SAXS revealed differences in the hydrated microstructure.

Conclusions

Even though S-PVA-C are highly attractive for encapsulation of rather hydrophilic formulations, some care is needed regarding an immediate release form. The type of formulation hydration must be considered for adequate selection of the capsule material.

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References

  1. Reich G. Formulation and physical properties of soft capsules. In: Podczeck F, Jones BE, editors. Pharmaceutical capsules. London: Pharmaceutical Press; 2004. p. 201–12.

    Google Scholar 

  2. Misic Z, Muffler K, Sydow G, Kuentz M. Novel starch-based PVA thermoplastic capsules for hydrophilic lipid-based formulations. J Pharm Sci. 2012;101:4516–28.

    Article  CAS  PubMed  Google Scholar 

  3. Lue BM, Nielsen FS, Magnussen T, Schou HM, Kristensen K, Jacobsen LO, et al. Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound. Eur J Pharm Biopharm. 2008;69:648–57.

    Article  CAS  PubMed  Google Scholar 

  4. Dressman J, Schamp K, Beltz K, Alsenz J. Characterizing release from lipid-based formulations. In: Hauss DJ, editor. Oral lipid-based formulations: enhancing the bioavailability of poorly water-soluble drugs. New York: Informa Healthcare USA, Inc.; 2007. p. 241–56.

    Google Scholar 

  5. Borst I, Ugwu S, Beckett AH. New and extended applications for USP drug release apparatus 3. Dissolution Technol. 1997;4(1):11–18.

    Google Scholar 

  6. Jantratid E, Janssen N, Chokshi H, Tang K, Dressman JB. Designing biorelevant release tests for lipid formulations: case example - lipid suspension of RZ-50. Eur J Pharm Biopharm. 2008;69:776–85.

    Article  CAS  PubMed  Google Scholar 

  7. Jantratid E, De Maio V, Ronda E, Mattavelli V, Vertzoni M, Dressman JB. Application of biorelevant release tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form. Eur J Pharm Sci. 2009;37:434–41.

    Article  CAS  PubMed  Google Scholar 

  8. Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nature Rev Drug Discov. 2007;6:231–48.

    Article  CAS  Google Scholar 

  9. Müllertz A, Ogbonna A, Ren S, Rades T. New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs. J Pharm Pharmacol. 2010;62:1622–36.

    Article  PubMed  Google Scholar 

  10. Lopez-Montilla JC, Herrera-Morales PE, Pandey S, Shah DO. Spontaneous emulsification: mechanisms, physicochemical aspects, modeling and applications. J Dispersion Sci Techn. 2002;23(1–3):219–68.

    CAS  Google Scholar 

  11. Wakerly MG, Pouton CW, Meakin BJ. Evaluation of the self-emulsifying performance of a non-ionic surfactant-vegetable oil mixture. J Pharm Pharmacol. 1987;39:6P.

    Google Scholar 

  12. Wakerly MG, Pouton CW, Meakin BJ, Morton FS. The effect of surfactant HLB on the self-emulsifying efficiency of non-ionic surfactant vegetable oil mixtures. J Pharm Pharmacol. 1987;38(S12):2P.

    Article  Google Scholar 

  13. Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Delivery Rev. 1997;25:47–58.

    Article  CAS  Google Scholar 

  14. Regev O, Ezrahi S, Aserin A, Garti N, Wachtel E, Kaler EW, et al. A study of the microstructure of a four-component nonionic microemulsion by cryo-TEM, NMR, SAXS, and SANS. Langmuir. 1996;12(3):668–74.

    Article  CAS  Google Scholar 

  15. Biradar SV, Dhumal RS, Paradkar A. Rheological investigation of self-emulsification process: effect of co-surfactant. J Pharm Pharmaceut Sci. 2009;12(2):164–74.

    CAS  Google Scholar 

  16. Patil SS, Venugopal E, Bhat S, Mahadik R, Paradkar AR. Probing influence of mesophasic transformation on performance of self-emulsifying system: effect of ion. Mol Pharmaceutics. 2012;9:318–24.

    Article  CAS  Google Scholar 

  17. Patil SS, Venugopal E, Bhat S, Mahadik R, Paradkar AR. Microstructural elucidation of self-emulsifying system: effect of chemical structure. Pharm Res. 2012;29(8):2180–8.

    Article  CAS  PubMed  Google Scholar 

  18. Fanun M. Oil type effect on diclofenac solubilization in mixed nonionic surfactants microemulsions. Colloids Surf, A: Physicochem Eng Aspects. 2009;343:75–82.

    Article  CAS  Google Scholar 

  19. Teubner M, Strey R. Origin of the scattering peak in microemulsions. J Chem Phys. 1987;87(5):3195–200.

    Article  CAS  Google Scholar 

  20. Klein S. Dissolution test methods for modified release dosage forms, Doctoral thesis. Frankfurt am Main: Shaker-Verlag; 2005.

  21. Yu LX, Wang JT, Hussain AS. Evaluation of USP apparatus 3 for dissolution testing of immediate-release products. AAPS Pharm Sci. 2002;4:1–5.

    Article  Google Scholar 

  22. Jantratid E, Janssen N, Reppas C, Dressman JB. Dissolution media simulating conditions in the proximal human gastrointestinal tract: an update. Pharm Res. 2008;25(7):1663–76.

    Article  CAS  PubMed  Google Scholar 

  23. Groves MJ. Rheological characterization of self-emulsifying oil/surfactant systems. Acta Pharm Suecica. 1976;13:353–60.

    CAS  Google Scholar 

  24. Pouton CW. Self-emulsifying drug delivery systems: assessment of the efficiency of emulsification. Int J Pharm. 1985;27:335–48.

    Article  CAS  Google Scholar 

  25. Rohrs BR, Burch-Clark DL, Witt MJ, Stelzer DJ. USP dissolution apparatus 3 (reciprocating cylinder): instrument parameter effects on drug release from sustained release formulations. J Pharm Sci. 1995;84:922–6.

    Article  CAS  PubMed  Google Scholar 

  26. The United States Pharmacopeia & The National Formulary. The Official Compendia of Standards, USP 35-NF30 2012. Pharmacopoeial Convention Inc., 2012.

  27. Fotaki N, Aivaliotis A, Butler J, Dressman J, Fischbach M, Hempenstall J, et al. A comparative study of different release apparatus in generating in vitro-in vivo correlations for extended release formulations. Eur J Pharm Biopharm. 2009;73:115–20.

    Article  CAS  PubMed  Google Scholar 

  28. Fanun M. Properties of microemulsions based on mixed nonionic surfactants and mixed oils. J Mol Liq. 2009;150:25–32.

    Article  CAS  Google Scholar 

  29. Mohsin K, Long MA, Pouton CW. Design of lipid-based formulations for oral administration of poorly water-soluble drugs: precipitation of drug after dispersion of formulations in aqueous solution. J Pharm Sci. 2009;98(10):3582–95.

    Article  CAS  PubMed  Google Scholar 

  30. Cabos C, Delord P, Marignan J. Local lamellar structure in dense microemulsions. Phys Rev B. 1988;37(16):9796–9.

    Article  CAS  Google Scholar 

  31. Kogan A, Shalev DE, Raviv U, Aserin A, Garti N. Formation and characterization of ordered bicontinuous microemulsions. J Phys Chem B. 2009;113:10669–78.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS AND DISCLOSURES

Financial support of the Swiss Caps AG (member of the Aenova group) is gratefully acknowledged.

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Authors and Affiliations

  1. Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland,, Gründenstr. 40, 4132, Muttenz, Switzerland

    Zdravka Misic & Martin Kuentz

  2. Department of Pharmaceutical Sciences, University of Basel, 4056, Basel, Switzerland

    Zdravka Misic

  3. Department of Chemistry, University of Basel,, Klingelbergstr. 80, 4056, Basel, Switzerland

    Raphael Urbani & Thomas Pfohl

  4. Swiss Caps AG member of the Aenova group,, Husenstr. 35, 9533, Kirchberg, Switzerland

    Katharina Muffler & Georg Sydow

Authors
  1. Zdravka Misic
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  2. Raphael Urbani
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  3. Thomas Pfohl
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  4. Katharina Muffler
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  5. Georg Sydow
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  6. Martin Kuentz
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Correspondence to Martin Kuentz.

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Misic, Z., Urbani, R., Pfohl, T. et al. Understanding Biorelevant Drug Release from a Novel Thermoplastic Capsule by Considering Microstructural Formulation Changes During Hydration. Pharm Res 31, 194–203 (2014). https://doi.org/10.1007/s11095-013-1152-y

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  • DOI: https://doi.org/10.1007/s11095-013-1152-y

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