Drug Delivery and Translational Research

, Volume 6, Issue 4, pp 380–391 | Cite as

Dissolution enhancement of atorvastatin calcium by co-grinding technique

Research Article
First Online:
  • 347 Downloads

Abstract

Atorvastatin calcium (AC) is a BCS class II drug which shows poor bioavailability due to inadequate dissolution. Solid dispersions present a promising option to enhance the solubility of poorly soluble drugs. Co-grinding with hydrophilic excipients is an easy and economical technique to improve the solubility of poorly soluble drugs and is free from usage of organic solvents. The aim of the present study was to explore novel carrier VBP-1 (organosulphur compound) for formulating a solid dispersion by using a simple, commercially viable co-grinding technique to enhance the dissolution of AC and to develop an oral formulation of the same. Composition of the solid dispersion was optimized based on the release profile in pH 1.2 buffer. The optimized solid dispersion was further characterized for flow properties, DSC, FTIR spectroscopy, XRD, contact angle, SEM studies and release profile in phosphate buffer pH 6.8. The developed solid dispersion gave similar release profile as the innovator formulation (Lipitor® tablets) in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed solid dispersion was formulated into hard gelatin capsules (size 3). The developed capsules were found to give similar release as the innovator formulation in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed capsules were found to be stable for a period of 6 months. Anti-hyperlipidemic efficacy studies in rats showed higher reduction in cholesterol and triglyceride levels by the developed capsules in comparison to pure AC. In conclusion, novel carrier VBP-1 was successfully employed to enhance the dissolution of AC using co-grinding technique.

Keywords

Atorvastatin calcium Co-grinding Solid dispersion Solubility Wettability Dissolution 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

The authors are thankful to University Grants Commission for Junior Research Fellowship. The authors also wish to thank Cadila Pharmaceuticals, Ahmedabad for the gift sample of AC; BASF, Mumbai for excipients and Haffkine Institute, Mumbai for providing the animals. The authors also thank Dr. Dalapathi Gugulothu, Dr. Harshad Shete, Dr. Soniya Jain, Jayesh Dhodi, Dr. S.S. Sathaye and Prof. A.R. Juvekar for their guidance in animal studies and Rubicon Research Private Limited, Mumbai for packaging of formulations.

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they do not have any competing interests.

References

  1. 1.
    O’ Driscoll CM, Griffin BT. Biopharmaceutical challenges associated with drugs with low aqueous solubility—the potential impact of lipid-based formulations. Adv Drug Deliv Rev. 2008;60:617–24.CrossRefGoogle Scholar
  2. 2.
    Bansal SS, Kaushal AM, Bansal AK. Molecular and thermodynamic aspects of solubility advantage from solid dispersions. Mol Pharm. 2007;4:794–802.CrossRefPubMedGoogle Scholar
  3. 3.
    Gorajana A, Rajendran A, Yew LM, Dua K. Preparation and characterization of cefuroxime axetil solid dispersions using hydrophilic carriers. Int J Pharm Invest. 2015;5:171–8.CrossRefGoogle Scholar
  4. 4.
    Garg A, Singh S, Rao VU, Bindu K, Balasubramaniam J. Solid state interaction of raloxifene HCl with different hydrophilic carriers during co-grinding and its effect on dissolution rate. Drug Dev Ind Pharm. 2009;35:455–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Vasconcelos T, Samento B, Costa P. Solid dispersions as a strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12:1068–75.CrossRefPubMedGoogle Scholar
  6. 6.
    Sethia S, Squillante E. Solid dispersions: revival with greater possibilities and applications in oral drug delivery. Crit Rev Ther Drug Carrier Syst. 2003;20:215–47.CrossRefPubMedGoogle Scholar
  7. 7.
    Liu J, Zou M, Piao H, Liu Y, Tang B, Gao Y, et al. Characterization and pharmacokinetic study of aprepitant solid dispersions with Soluplus®. Molecules. 2015;20:11345–56.CrossRefPubMedGoogle Scholar
  8. 8.
    Nikghalb LA, Singh G, Singh G, Kahkeshan KF. Solid dispersion: methods and polymers to increase the solubility of poorly soluble drugs. J Appl Pharm Sci. 2012;2:170–5.Google Scholar
  9. 9.
    Barzegar-Jalali M, Valizadeh H, Dastmalchi S, Shadbad MRS, Barzegar-Jalali A, Adibkia K, et al. Enhancing dissolution rate of carbamazepine via cogrinding with crosspovidone and hydroxypropylmethylcellulose. Iran J Pharm Res. 2007;6:159–65.Google Scholar
  10. 10.
    Vogt M, Kunath K, Dressman JB. Dissolution enhancement of fenofibrate by micronization, cogrinding and spray-drying: comparison with commercial preparations. Eur J Pharm Biopharm. 2008;68:283–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Sugimoto M, Okagaki T, Narisawa S, Koida Y, Nakajima K. Improvement of dissolution characteristics and bioavailability of poorly water-soluble drugs by novel cogrinding method using water-soluble polymer. Int J Pharm. 1998;160:11–9.CrossRefGoogle Scholar
  12. 12.
    Barzegar-Jalali M, Valizadeh H, Shadbad MRS, Adibkia K, Mohammadi G, Farahani A, et al. Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide). Powder Technol. 2010;197:150–8.CrossRefGoogle Scholar
  13. 13.
    Vadher AH, Parikh JR, Parikh RH, Solanki AB. Preparation and characterization of Co-grinded mixtures of aceclofenac and neusilin US2 for dissolution enhancement of aceclofenac. AAPS PharmSciTech. 2009;10:606–14.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Penkina A, Semjonov K, Hakola M, Vuorinen S, Repo T, Yliruusi J, Aruvali J, Kogermann K, Veski P, Heinamaki J. Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers. Drug Dev. Ind. Pharm. 2015; doi:10.3109/03639045.2015.1054400Google Scholar
  15. 15.
    Ahmed T, Kollipara S, Gautam A, Gigras R, Kothari M, Saha N, et al. Bioavailability and interaction potential of atorvastatin and losartan on co-administration in healthy human subjects. J Bioequiv Availab. 2009;1:18–27.Google Scholar
  16. 16.
    Arunkumar N, Deecaraman M, Rani C, Mohanraj KP, Kumar KV. Preparation and solid state characterization of atorvastatin nanosuspensions for enhanced solubility and dissolution. Int J PharmTech Res. 2009;1:1725–30.Google Scholar
  17. 17.
    Kim MS, Jin SJ, Kim JS, Park HJ, Song HS, Neubert RHH, et al. Preparation, characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process. Eur J Pharm Biopharm. 2008;69:454–65.CrossRefPubMedGoogle Scholar
  18. 18.
    Yin YM, Cui FD, Kim JS, Choi MK, Choi BC, Chung SJ, et al. Preparation, characterization and in vitro intestinal absorption of a dry emulsion formulation containing atorvastatin calcium. Drug Deliv. 2009;16:30–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Atorvastatin Calcium Tablets, Indian Pharmacopeia, 2010, A publication of Indian Pharmacopoeia Commission, Sixth edition, Volume II, 850Google Scholar
  20. 20.
    Yuan Y, Lee TR. Contact angle and wetting properties. In: Bracco G, Holst B, editors. Surface Science Techniques. Germany: Springer Berlin Heidelberg; 2013. pp. 1–35.Google Scholar
  21. 21.
    Patel AR, Vavia PR. Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate. AAPS J. 2007;9:E344–52.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sonar PA, Behera AL, Banerjee SK, Gaikwad DD, Harer SL. Preparation and characterization of simvastatin solid dispersion using skimmed milk. Drug Dev Ind Pharm. 2015;41:22–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Uniformity of Weight of Single-Dose Preparations in Pharmaceutical Methods, Indian Pharmacopeia, 2010, A publication of Indian Pharmacopoeia Commission, Sixth edition, Volume I, 192Google Scholar
  24. 24.
    Disintegration Test in Pharmaceutical Methods, Indian Pharmacopeia, 2010, A publication of Indian Pharmacopoeia Commission, Sixth edition, Volume I, 187–188Google Scholar
  25. 25.
    Krishnamoorthy V, Prasad VPR, Sen S. Studies on clozapine-mannitol solid dispersions, physicochemical characterization and evaluation. Turkish J Pharm Sci. 2013;10:109–24.Google Scholar
  26. 26.
    Newa M, Bhandari KH, Li DX, Kwon TH, Kim JA, Yoo BK, et al. Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. Int J Pharm. 2007;343:228–37.CrossRefPubMedGoogle Scholar
  27. 27.
    Sruti J, Patra CN, Swain SK, Beg S, Palatasingh HR, Dinda SC, et al. Improvement in dissolution rate of cefuroxime axetil by using poloxamer 188 and neusilin US2. Indian J Pharm Sci. 2013;75:67–75.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Chen Y, Zhang GGZ, Neilly J, Marsh K, Mawhinney D, Sanzgiri YD. Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68. Int J Pharm. 2004;286:69–80.CrossRefPubMedGoogle Scholar
  29. 29.
    Badjatya JK, Bodla RB, Solanki S, Kumar D. Enhancement of solubility of paclitaxel by solid dispersions techniques. Asian J Pharm Life Sci. 2011;1:156–60.Google Scholar
  30. 30.
    Shah S, Joshi S, Lin S, Madan PL. Preparation and characterization of spironolactone solid dispersions using hydrophilic carriers. Asian J Pharm Sci. 2012;7:40–9.Google Scholar
  31. 31.
    Patel B, Parikh RH, Swarnkar D. Enhancement of dissolution of telmisartan through use of solid dispersion technique-surface solid dispersion. J Pharm Bioall Sci. 2012;4:64–8.CrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2015

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences and TechnologyInstitute of Chemical TechnologyMumbaiIndia

Personalised recommendations