AAPS PharmSciTech

, Volume 11, Issue 2, pp 518–527 | Cite as

Solid Dispersion as an Approach for Bioavailability Enhancement of Poorly Water-Soluble Drug Ritonavir

  • Shilpi Sinha
  • Mushir Ali
  • Sanjula Baboota
  • Alka Ahuja
  • Anil Kumar
  • Javed Ali
Research Article


Ritonavir is an antiretroviral drug characterized by low solubility and high permeability which corresponds to BCS class II drug. The purpose of the study was to develop solid dispersion by different methods and investigate them for in vitro and in vivo performance for enhancing dissolution and bioavailability, respectively. Since the drug possesses food-related absorption, the effect of biorelevant media (FaSSIF and FeSSIF state) on dissolution behavior was also studied. The solid dispersion was prepared using Gelucire as carrier in 1:4 ratio by different methods and were characterized for differential scanning calorimetry (DSC), X-ray diffractometry, scanning electron microscopy, and FT-IR. Oral bioavailability of 10 mg of ritonavir in solid dispersion prepared by solvent evaporation (SE1) and melt method (MM1) was compared with pure drug after oral administration of solid dispersion and pure drug to Albino Wistar rats of either sex. The results suggested formation of eutectic solid dispersion. In vitro dissolution studies was performed in 0.1 N HCl and biorelevant media showed enhanced dissolution rate as compared to pure drug in both FeSSIF media and 0.1 N HCl. The apparent rate of absorption of ritonavir from SE1 (Cmax 20221.37 ng/ml, tmax 0.5 h) was higher than that of MM1 (Cmax 2,462.2, tmax 1 h) and pure drug (Cmax 1,354.8 ng/ml, tmax 0.5 h). On the basis of the result obtained, it was concluded that solid dispersion is a good approach to enhance solubility and bioavailability of poorly water-soluble ritonavir.

Key words

bioavailability gelucire poorly soluble drug ritonavir solid dispersion 


  1. 1.
    Lipinski CA, Lombardo F, Dominyl BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23:3–25. doi:10.1016/S0169-409X(96)00423-1.CrossRefGoogle Scholar
  2. 2.
    Dannenfelser R, He H, Joshi Y, Bateman S, Serajuddin ATM. Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci. 2004;93:1165–75. doi:10.1002/jps.20044.CrossRefPubMedGoogle Scholar
  3. 3.
    Mooter GVD, Augustijns P, Blaton N, Kinget R. Physico-chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int J Pharm. 1998;164:67–80. doi:10.1016/S0378-5173(97)00401-8.CrossRefGoogle Scholar
  4. 4.
    Habib MJ. Pharmaceutical solid dispersion technology. Washington: CRC; 2000. p. 35–78.Google Scholar
  5. 5.
    Law D, Krill SL, Schmitt EA, Fort JJ, Qiu Y, Wang W et al. Physicochemical considerations in the preparation of amorphous ritonavir-poly (ethylene glycol) 8000 solid dispersions. J Pharm Sci. 2000;90:1015–25. doi:10.1002/jps.1054.CrossRefGoogle Scholar
  6. 6.
    Pignatello R, Ferro M, Guidi GD, Salemi G, Vandelli MA, Guccione S et al. Preparation, characterisation and photosensitivity studies of solid dispersions of diflunisal and Eudragit RS100 and RL100. Int J Pharm. 2001;218:27–42. doi:10.1016/S0378-5173(01)00597-X.CrossRefPubMedGoogle Scholar
  7. 7.
    Babu GVM, Prasad DS, Murthy KVR. Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug Nimodipine. Int J Pharm. 2002;234:1–17. doi:10.1016/S0378-5173(01)00925-5.CrossRefGoogle Scholar
  8. 8.
    Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86:1–12. doi:10.1021/js9601896.CrossRefPubMedGoogle Scholar
  9. 9.
    Gowariker VR, Viswanathan NV, Sreedhar J. Polymer science. New Delhi: New Age; 1986. p. 150–79.Google Scholar
  10. 10.
    Serajuddin ATM. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88:1058–66. doi:10.1021/js980403l.CrossRefPubMedGoogle Scholar
  11. 11.
    Barker SA, Yap SP, Yuen KH, McCoy CP, Murphy JR, Craig DQM. An investigation in to structure and bioavailability of α-tocopherol in Gelucire 44/14. J Control Release. 2003;91:477–88. doi:10.1016/S0168-3659(03)00261-X.CrossRefPubMedGoogle Scholar
  12. 12.
    Nilüfer Y, Aysegül K, Yalçın Ö, Ayhan S, Sibel AÖ, Tamer B. Enhanced bioavailability of piroxicam using Gelucire 44/14 and Labrasol: in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2003;56:453–9. doi:10.1016/S0939-6411(03)00142-5.CrossRefGoogle Scholar
  13. 13.
    Ozkan Y, Doganay N, Dikmen N, Isimer A. Enhanced release of solid dispersions of etodolac in polyethylene glycol. Farmaco. 2000;55:433–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Damian F, Blaton N, Naesens L, Balzarini J, Kinget R, Augustijns P et al. Physicochemical characterization of solid dispersions of the antiviral agent UC-781 with polyethylene glycol 6000 and Gelucire 44/14. Eur J Pharm Sci. 2000;10:311–22. doi:10.1016/S0928-0987(00)00084-1.CrossRefPubMedGoogle Scholar
  15. 15.
    Kanaze FI, Kokkalou E, Niopas I, Georgarakis M, Stergiou A, Bikiaris D. Novel drug delivery systems for flavonoid compounds with enhanced solubility based on solid dispersions with polyvinylpyrolidone and polyethyleneglycol. J Appl Polym Sci. 2006;102:460–71. doi:10.1002/app. 24200.CrossRefGoogle Scholar
  16. 16.
    Sekar V, Kestens D, Spinosa-Guzman S. The effect of different meal types on the pharmacokinetics of Darunavir (TMC114)/Ritonavir in HIV-Negative Healthy Volunteers. J Clin Pharmacol. 2007;47:479–84.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  • Shilpi Sinha
    • 1
  • Mushir Ali
    • 2
  • Sanjula Baboota
    • 2
  • Alka Ahuja
    • 2
  • Anil Kumar
    • 2
  • Javed Ali
    • 2
  1. 1.Department of Analytical Research DevelopmentJubilant OrganosysNoidaIndia
  2. 2.Department of Pharmaceutics, Faculty of PharmacyHamdard UniversityNew DelhiIndia

Personalised recommendations