Skip to main content
SpringerLink
Log in

Application of Pharmaceutical QbD for Enhancement of the Solubility and Dissolution of a Class II BCS Drug using Polymeric Surfactants and Crystallization Inhibitors: Development of Controlled-Release Tablets

  • Research Article
  • Theme: Advanced Technologies for Oral Controlled Release
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of felodipine solid mixture (FSM) containing hydrophilic carriers and/or polymeric surfactants, for easier development of controlled-release tablets of felodipine. The material attributes, the process parameters (CPP), and the critical quality attributes of the FSMs were identified. Box–Behnken experimental design was applied to develop space design and determine the control space of FSMs that have maximum solubility, maximum dissolution, and ability to inhibit felodipine crystallization from supersaturated solution. Material attributes and CPP studied were the amount of hydroxypropyl methylcellulose (HPMC; X 1), amount of polymeric surfactants Inutec®SP1 (X 2), amount of Pluronic®F-127 (X 3) and preparation techniques, physical mixture (PM) or solvent evaporation (SE; X 4). There is no proposed design space formed if the Pluronic® content was below 45.1 mg and if PM is used as the preparation technique. The operating ranges, for robust development of FSM of desired quality, of Pluronic®, Inutec®SP1, HPMC, and preparation technique, are 49–50, 16–23, 83–100 mg, and SE, respectively. The calculated value of f2 was 56.85, indicating that the release profile of the controlled-release (CR) tablet (CR-6) containing the optimized in situ-formed FSM was similar to that of the target release profile. Not only did the ternary mixture of Pluronic®, HPMC with Inutec®SP1 enhance the dissolution rate and inhibit crystallization of felodipine, but also they aided Carbopol®974 in controlling felodipine release from the tablet matrix. It could be concluded that a promising once-daily CR tablets of felodipine was successfully designed using QbD approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Nasr M. FDA’s quality initiatives: an update. http://www.gmpcompliance.com/daten/download/FDAs_Quality_Initiative.pdf. Accessed 18 Nov 2010.

  2. Food and Drug Administration CDER. Guidance for industry, Q8 (R2) pharmaceutical development (November 2009).

  3. Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25(4):781–91.

    Article  PubMed  CAS  Google Scholar 

  4. Lee KR, Kim EJ, Seo SW, Choi HK. Effect of poloxamer on the dissolution of felodipine and preparation of controlled release matrix tablets containing felodipine. Arch Pharm Res. 2008;31(8):1023–8.

    Article  PubMed  CAS  Google Scholar 

  5. Kerc J, Srcic S, Knez Z, Sencar-Bozic P. Micronization of drugs using supercritical carbon dioxide. Int J Pharm. 1999;182(1):33–9.

    Article  PubMed  CAS  Google Scholar 

  6. Karavas E, Ktistis G, Xenakis A, Georgarakis E. Miscibility behavior and formation mechanism of stabilized felodipine-polyvinylpyrrolidone amorphous solid dispersions. Drug Dev Ind Pharm. 2005;31(6):473–89.

    Article  PubMed  CAS  Google Scholar 

  7. Karavas E, Georgarakis E, Sigalas MP, Avgoustakis K, Bikiaris D. Investigation of the release mechanism of a sparingly water-soluble drug from solid dispersions in hydrophilic carriers based on physical state of drug, particle size distribution and drug–polymer interactions. Eur J Pharm Biopharm. 2007;66(3):334–47.

    Article  PubMed  CAS  Google Scholar 

  8. Kim EJ, Chun MK, Jang JS, Lee IH, Lee KR, Choi HK. Preparation of a solid dispersion of felodipine using a solvent wetting method. Eur J Pharm Biopharm. 2006;64(2):200–5.

    Article  PubMed  CAS  Google Scholar 

  9. Vogt M, Kunath K, Dressman JB. Dissolution improvement of four poorly water soluble drugs by cogrinding with commonly used excipients. Eur J Pharm Biopharm. 2008;68:330–7.

    Article  PubMed  CAS  Google Scholar 

  10. Konno H, Taylor LS. Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J Pharm Sci. 2006;95(12):2692–705.

    Article  PubMed  CAS  Google Scholar 

  11. Konno H, Taylor LS. Ability of different polymers to inhibit the crystallization of amorphous felodipine in the presence of moisture. Pharm Res. 2007;25(4):969–78.

    Article  PubMed  Google Scholar 

  12. Konno H, Handa T, Alonzo DE, Taylor LS. Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur J Pharm Biopharm. 2008;70:493–9.

    Article  PubMed  CAS  Google Scholar 

  13. Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK. Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm. 2008;68(3):513–25.

    PubMed  CAS  Google Scholar 

  14. Won DH, Kim MS, Lee S, Park JS, Hwang SJ. Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process. Int J Pharm. 2005;301(1–2):199–208.

    Article  PubMed  CAS  Google Scholar 

  15. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27(1):48–9.

    Article  PubMed  CAS  Google Scholar 

  16. Furlanetto S, Cirri M, Maestrelli F, Corti G, Mura P. Study of formulation variables influencing the drug release rate from matrix tablets by experimental design. Eur J Pharm Biopharm. 2006;62:77–84.

    Article  PubMed  CAS  Google Scholar 

  17. Janssens S, Humbeeck JV, Van den Mooter G. Evaluation of the formulation of solid dispersions by co-spray drying itraconazole with Inutec SP1, a polymeric surfactant, in combination with PVPVA 64. Eur J Pharm Biopharm. 2008;70(2):500–5.

    Article  PubMed  CAS  Google Scholar 

  18. Chutimaworapan S, Ritthidej GC, Yonemochi E, Oguchi T, Yamamoto K. Effect of water-soluble carriers on dissolution characteristics of nifedipine solid dispersions. Drug Dev Ind Pharm. 2000;26(11):1141–50.

    Article  PubMed  CAS  Google Scholar 

  19. Chen J, Qiu L, Hu M, Jin Y, Han J. Preparation, characterization and in vitro evaluation of solid dispersions containing docetaxel. Drug Dev Ind Pharm. 2008;34(6):588–94.

    Article  PubMed  CAS  Google Scholar 

  20. Van den Mooter G, Weuts I, De Ridder T, Blaton N. Evaluation of Inutec SP1 as a new carrier in the formulation of solid dispersions for poorly soluble drugs. Int J Pharm. 2006;316(1–2):1–6.

    Article  PubMed  Google Scholar 

  21. Ghebremeskel AN, Vemavarapu C, Lodaya M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: selection of polymer–surfactant combinations using solubility parameters and testing the processability. Int J Pharm. 2007;328(2):119–29.

    Article  PubMed  CAS  Google Scholar 

  22. Matsumoto T, Zografi G. Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm Res. 1999;16(11):1722–8.

    Article  PubMed  CAS  Google Scholar 

  23. Simonelli AP, Mehta SC, Higuchi WI. Dissolution rates of high energy sulfathiazole–povidone coprecipitates II: characterization of form of drug controlling its dissolution rate via solubility studies. J Pharm Sci. 1976;65(3):355–61.

    Article  PubMed  CAS  Google Scholar 

  24. Suzuki H, Sunada H. Influence of water-soluble polymers on the dissolution of nifedipine solid dispersions with combined carriers. Chem Pharm Bull (Tokyo). 1998;46(3):482–7.

    CAS  Google Scholar 

  25. Raghavan SL, Trividic A, Davis AF, Hadgraft J. Crystallization of hydrocortisone acetate: influence of polymers. Int J Pharm. 2001;212(2):213–21.

    Article  PubMed  CAS  Google Scholar 

  26. Usui F, Maeda K, Kusai A, Nishimura K, Yamamoto K. Inhibitory effects of water-soluble polymers on precipitation of RS-8359. Int J Pharm. 1997;154:59–66.

    Article  CAS  Google Scholar 

  27. Khan GM, Jiabi Z. Formulation and in vitro evaluation of ibuprofen-Carbopol 974P-NF controlled release matrix tablets III: influence of co-excipients on release rate of the drug. J Control Release. 1998;54(2):185–90.

    Article  PubMed  CAS  Google Scholar 

  28. Rodriguez CF, Bruneau N, Barra J, Alfonso D, Doelker E. Hydrophilic cellulose derivatives as drug delivery carriers: influence of the substitution type on the properties of compressed matrix tablets. In: Wise DL, editor. Handbook of pharmaceutical controlled release technology. New York, USA: Marcell Dekker; 2000. p. 1–30.

    Google Scholar 

  29. Maggi L, Bruni R, Conte U. High molecular weight polyethylene oxides (PEOs) as an alternative to HPMC in controlled release dosage forms. Int J Pharm. 2000;195(1–2):229–38.

    Article  PubMed  CAS  Google Scholar 

  30. Ozeki T, Yuasa H, Kanaya Y. Controlled release from solid dispersion composed of poly(ethylene oxide)-carbopol interpolymer complex with various cross-linking degrees of carbopol. J Control Release. 2000;63(3):287–95.

    Article  PubMed  CAS  Google Scholar 

  31. Aboelwafa AA, Basalious EB. Optimization and in vivo pharmacokinetic study of a novel controlled release venlafaxine hydrochloride three-layer tablet. AAPS Pharm Sci Tech. 2010;11(3):1026–37.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt

    Emad B. Basalious, Wessam El-Sebaie & Omaima El-Gazayerly

Authors
  1. Emad B. Basalious
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wessam El-Sebaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Omaima El-Gazayerly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emad B. Basalious.

Additional information

Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

Rights and permissions

Reprints and permissions

About this article

Cite this article

Basalious, E.B., El-Sebaie, W. & El-Gazayerly, O. Application of Pharmaceutical QbD for Enhancement of the Solubility and Dissolution of a Class II BCS Drug using Polymeric Surfactants and Crystallization Inhibitors: Development of Controlled-Release Tablets. AAPS PharmSciTech 12, 799–810 (2011). https://doi.org/10.1208/s12249-011-9646-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-011-9646-6

Key words

Search

Navigation