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Co-solvent Evaporation Method for Enhancement of Solubility and Dissolution Rate of Poorly Aqueous Soluble Drug Simvastatin: In vitroIn vivo Evaluation

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Abstract

A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility, dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer hydroxypropyl methylcellulose (HPMC K3LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of HPMC K3LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy, and Fourier-transform infrared spectroscopy. In vitroin vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM.

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References

  1. H. G. Brittain. Analytical Profiles of Drug Substances and Excipients, vol. 22, Academic, New York, 2003, p. 36.

  2. J. C. Feeley, P. York, B. S. Sumby, and H. Dicks. Determination of surface properties and flow characteristics of salbutamol sulphate, before and after micronisation. Int. J. Pharm. 172:89–96 (1998).

    Article  CAS  Google Scholar 

  3. J. Szejtli. Cyclodextrin Technology, Kluwer, Amsterdam, 1993.

    Google Scholar 

  4. W. L. Chiou, and S. Riegelman. Pharmaceutical application of solid dispersion system. J. Pharm. Sci. 60:1281–1302 (1971).

    Article  PubMed  CAS  Google Scholar 

  5. A. T. M. Serajuddin. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J. Pharma. Sci. 159:85–93 (1999).

    Google Scholar 

  6. H. El-Zein, L. Riad, and A. A. El-Bary. Enhancement of carbamazepine dissolution: in vitro and in vivo evaluation. Int. J. Pharm. 168:209–220 (1998).

    Article  CAS  Google Scholar 

  7. A. S. Narang, and A. K. Srivastava. Evaluation of solid dispersions of clofazimine. Drug Dev. Ind. Pharm. 28:1001–1013 (2002).

    Article  PubMed  CAS  Google Scholar 

  8. M. Sumnu. Increasing dissolution rate and gastrointestinal absorption of nifidipine via solid dispersion. STP Pharma. 2:214–220 (1986).

    CAS  Google Scholar 

  9. P. Mura, M. T. Faucci, A. Manderioli, G. Bramanti, and L. Ceccarelli. Properties of solid dispersion of naproxen in various polyethylene glycols. Drug Del. Ind. Pharm. 22:909–916 (1996).

    Article  CAS  Google Scholar 

  10. D. H. Doshi, W. R. Ravis, and G. V. Betageri. Carbamazepine and polyethylene glycol solid dispersion: preparation’ in vitro dissolution, and characterization. Drug Del. Ind. Pharm. 23:1167–1176 (1997).

    Article  CAS  Google Scholar 

  11. P. Mura, M. T. Faucci, A. Manderioli, G. Bramanti, and P. Parrini. Thermal behaviour and dissolution properties of naproxen from binary and ternary solid dispersions. Drug Del. Ind. Pharm. 25:257–264 (1999).

    Article  CAS  Google Scholar 

  12. G. Yan, H. Li, R. Zhang, and D. Ding. Preparation and evaluation of a sustained-release formulation of nifedipine HPMC tablets. Drug Del. Ind. Pharm. 26:681–686 (2000).

    Article  CAS  Google Scholar 

  13. E. Broman, C. Khoo, and L. S. Taylor. A comparison of alternative polymer excipients and processing methods for making solid dispersion of poorly water soluble drug. Int. J. Pharm. 222:139–151 (2001).

    Article  PubMed  CAS  Google Scholar 

  14. H. M. Aliabadi, and A. Lavasanifar. Polymeric micelles for drug delivery. Expert Opin. Drug Del. 3:139–162 (2006).

    Article  CAS  Google Scholar 

  15. S. W. Jun, M. S. Kim, J. S. Kim, and S. J. Hwang. Preparation and characterization of Simvastatin/hydroxypropyl- β -cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. Eur. J. Pharm. Biopharm. 66:413–421 (2007).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are very thankful to Artimis Biotech, IDA, Jeedimetla, Hyderabad, India and hydroxylpropyl methylcellulose K3LV (HPMC K3LV) Colorcon Asia Limited, Verna, Goa, India, for providing gift samples of Simvastatin and HPMC K3LV, respectively.

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Correspondence to Surendra Gattani.

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Pandya, P., Gattani, S., Jain, P. et al. Co-solvent Evaporation Method for Enhancement of Solubility and Dissolution Rate of Poorly Aqueous Soluble Drug Simvastatin: In vitroIn vivo Evaluation. AAPS PharmSciTech 9, 1247–1252 (2008). https://doi.org/10.1208/s12249-008-9176-z

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  • DOI: https://doi.org/10.1208/s12249-008-9176-z

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