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Enhancement in Dissolution Rate of Atorvastatin Trihydrate Calcium by Formulating Its Porous Tablet Using Sublimation Technique

  • Shikha Y. Singh
  • Salwa
  • Rupesh K. Shirodkar
  • Ruchi Verma
  • Lalit KumarEmail author
Original Article
  • 27 Downloads

Abstract

Objective

Proposed study was aimed to formulate and evaluate atorvastatin trihydrate calcium porous tablet.

Methods

Since atorvastatin trihydrate calcium is highly unstable drug and is immensely susceptible to hydrolysis and oxidation process, sublimation technique is taken into account for preparing porous tablet by using direct compression technique. Excipient screening and pre-formulation study was conducted to evaluate the presence of drug-excipient compatibility. Formulation was optimised using central composite design (CCD) and optimized batch was further characterised by scanning electron microscopy (SEM) for identification of surface topography. Optimized formulation was also characterised with respect to FTIR, TGA analysis, compression analysis, in vitro drug release studies and stability studies.

Results

Hardness, friability, disintegration time and drug content of optimized porous tablets were found to be 3.46 kg/cm2, 0.92%, 7.23 s and 97.00%, respectively. Compression analysis showed optimized formulation powder is soft and plastic in nature. Tensile strength studies revealed that the tensile strength increases with increase in compression pressure. SEM studies confirmed the presence of number of pores with less than 10 μm pore size. FTIR and TGA studies confirmed that there is no change in chemical structure of drug even in porous tablet. Prepared porous tablets released 85.06 ± 15.55% of drug in 25 min whereas immediate release marketed tablets and pure drug released only 59.13 ± 4.78% and 11.36 ± 2.90% of drug in a same time. The release of proposed dosage form was substantially greater than the marketed product. Preliminary profile of stability studies did not show any significant change (p > 0.05) in the results after 90 days.

Conclusion

Porous tablets improved release rate which confirmed that this approach may be useful to enhance the dissolution rate of atorvastatin trihydrate calcium.

Keywords

Porous tablet Porous matrix Porous drug delivery system Fast dissolving tablet Thermogravimetric analysis Heckel compression analysis Kawakita compression analysis Atorvastatin trihydrate calcium Enhanced drug release Solubility and dissolution 

Notes

Acknowledgements

The authors are thankful to Dr. Reddy Laboratories, Hyderabad, for providing atorvastatin trihydrate calcium as a gift sample. Authors gratefully acknowledge the help of Dr. Praveen Khullar, Mr. D. Saravanan and Dr. Prakash Muthudoss, Sanofi-Synthelabo (India) Pvt. Ltd., Verna, Goa, for thermogravimetric analysis of samples. Authors are thankful to Flamingo Pharmaceutical Ltd., Mumbai, for Karl Fisher Titrimetry study. Authors are also thankful to Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education and Goa College of Pharmacy for providing the infrastructural facilities to complete this work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    Cosijns A, Vervaet C, Luyten J, Mullens S, Siepmann F, van Hoorebeke L, et al. Porous hydroxyapatite tablets as carriers for low-dosed drugs. Eur J Pharm Biopharm. 2007;67(2):498–506.CrossRefGoogle Scholar
  2. 2.
    Ahjel SW, Lupuleasa D. Enhancement of solubility and dissolution rate of different forms of atorvastatin calcium in direct compression tablet formulas. Farmacia. 2009;57(3):290–300.Google Scholar
  3. 3.
    Rodde MS, Divase GT, Devkar TB, Tekade AR. Solubility and bioavailability enhancement of poorly aqueous soluble atorvastatin: in vitro, ex vivo, and in vivo studies. Biomed Res Int. 2014;2014(463895):11.Google Scholar
  4. 4.
    Geethalakshmi A, Divya V, Mahalingan K. Enhancement of solubility and dissolution rate of atorvastatin calcium by co-solvent evaporation. World J Pharm Pharm Sci. 2013;2(5):3790–806.Google Scholar
  5. 5.
    Wicaksono Y, Wisudyaningsih B, Siswoyo TA. Enhancement of solubility and dissolution rate of atorvastatin calcium by co-crystallization. Trop J Pharm Res. 2017;16(7):1497–502.CrossRefGoogle Scholar
  6. 6.
    Sharma Y, Kumar K, Padhy SK. Formulation and evaluation of atorvastatin calcium niosomes. Int J Life Sci Scienti Res. 2016;2(4):462–5.Google Scholar
  7. 7.
    Bora D, Borude P, Bhise K. Formulation and evaluation of self microemulsifying drug delivery systems of low solubility drug for enhanced solubility and dissolution. Asian J Biomed Pharm Sci. 2012;2(15):7–14.Google Scholar
  8. 8.
    Ajmeral A, Deshpande S, Kharadi S, et al. Dissolution rate enhancement of atorvastatin, fenofibrate and ezetimibe by inclusion complex with β-cyclodextrin. Asian J Pharm Clin Res. 2012;5(4):73–6.Google Scholar
  9. 9.
    Kulkarni MC, Kolhe SV. Formulation development and evaluation of atorvastatin calcium tablets using co-processed excipients. Int J Pharm Sci Rev Res. 2016;36(1):217–22.Google Scholar
  10. 10.
    Gubbi SR, Jarag R. Formulation and characterization of atorvastatin calcium liquisolid compacts. Asian J Pharm Sci. 2010;5(2):50–60.Google Scholar
  11. 11.
    Chandiran IS, Anandakirouchenane E. Enhancement of solubility of atorvastatin calcium by nanosuspension technique. Int J Biopharm. 2014;5(3):214–7.Google Scholar
  12. 12.
    Hasson KJ. Enhancement of atorvastatin tablet dissolution using acid medium. Iraqi J Pharm Sci. 2010;19(1):82–5.Google Scholar
  13. 13.
    Maniya NH, Patel SR, Murthy ZVP. Drug delivery with porous silicon films, microparticles and nanoparticles. Rev Adv Mater Sci. 2016;44:257–72.Google Scholar
  14. 14.
    Markl D, Wang P, Ridgway C, Karttunen AP, Chakraborty M, Bawuah P, et al. Characterization of the pore structure of functionalized calcium carbonate tablets by terahertz time-domain spectroscopy and X-ray computed microtomography. J Pharm Sci. 2017;106:1586–95.CrossRefGoogle Scholar
  15. 15.
    Zhou M, Shen L, Lin X, Hong Y, Feng Y. Design and pharmaceutical applications of porous particles. RSC Adv. 2017;7:39490–501.CrossRefGoogle Scholar
  16. 16.
    Sharma S, Sher P, Badve S, et al. Adsorption of meloxicam on porous calcium silicate: characterization and tablet formulation. AAPSPharmSciTech. 2005;6(4):E618–25.Google Scholar
  17. 17.
    Ishikawa T, Watanabe Y, Utoguchi N, et al. Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method. Chem Pharm Bull. 1999;47(10):1451–4.CrossRefGoogle Scholar
  18. 18.
    Koizumi K, Watanabe Y, Morita K, Utoguchi N, Matsumoto M. New method of preparing high-porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material. Int J Pharm. 1997;152(1):127–31.CrossRefGoogle Scholar
  19. 19.
    Singh SS, Verma R, Kumar L. Porous oral drug delivery system—tablets. Pharm Chem J. 2018. 52(6):553–61.Google Scholar
  20. 20.
    Porosity and its influence on pharmaceutical tablet dissolution profiles, 2017. Available at: https://www.azom.com/article.aspx? ArticleID=13574. Accessed on May 28, 2018.
  21. 21.
    Quodbach J, Kleinebudde P. A critical review on tablet disintegration. Pharm Dev Technol. 2016;21(6):763–74.Google Scholar
  22. 22.
    Podczeck F. Methods for the practical determination of the mechanical strength of tablets—from empiricism to science. Int J Pharm. 2012;436:214–32.CrossRefGoogle Scholar
  23. 23.
    Thoorens G, Krier F, Leclercq B, Carlin B, Evrard B. Microcrystalline cellulose, a direct compression binder in a quality by design environment—a review. Int J Pharm. 2014;473:64–72.CrossRefGoogle Scholar
  24. 24.
    Hasegawa M. Direct compression: microcrystalline cellulose grade 12 versus classic grade 102. Pharm Technol. 2002;26:50–60.Google Scholar
  25. 25.
    Estibeiro AL, Harmalkar D, Godinho S, et al. Lacidipine porous tablets: formulation and in vitro characterization. Lat Am J Pharm. 2018;37:1764–71.Google Scholar
  26. 26.
    Shirsand SB, Suresh S, Kusumdevi V, Swamy PV. Formulation design and optimization of fast dissolving clonazepam tablets by sublimation method. Indian J Pharm Sci. 2011;73:491–6.CrossRefGoogle Scholar
  27. 27.
    Jeevanandham S, Dhachinamoorthi D, Chandra Sekhar KB, Muthukumaran M, Sriram N, Joysaruby J. Formulation and evaluation of naproxen sodium orodispersible tablets—a sublimation technique. Asian J Pharm. 2010;Jan-Mar;4:48–51.CrossRefGoogle Scholar
  28. 28.
    Elbary AA, Ali AA, Aboud HM. Enhanced dissolution of meloxicam from orodispersible tablets prepared by different methods. Bull Faculty Pharm Cairo Univ. 2012;50:89–97.CrossRefGoogle Scholar
  29. 29.
    Barnes TJ, Jarvis KL, Prestidge CA. Recent advances in porous silicon technology for drug delivery. Ther Deliv. 2013;4(7):811–23.CrossRefGoogle Scholar
  30. 30.
    Srinivas NSK, Verma R, Kulyadi GP, et al. A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro and in vivo characterization. Int J Nanomed. 2017;12:15–28.CrossRefGoogle Scholar
  31. 31.
    Kumar L, Reddy MS, Managuli RS, et al. Full factorial design for optimization, development and validation of HPLC method to determine valsartan in nanoparticles. Saudi Pharm J. 2015;23(5):549–55.CrossRefGoogle Scholar
  32. 32.
    Kumar L, Reddy MS, Shirodkar RK, Pai GK, Krishna VT, Verma R. Preparation and characterization of fluconazole vaginal films for the treatment of vaginal candidiasis. Indian J Pharm Sci. 2013;75(5):585–90.Google Scholar
  33. 33.
    Venugopal P, Gnanaprakash K, Kumar B, et al. Development of formulation and evaluation of ramipril porous tablet by sublimation technique. Int J Biopharm. 2014;5(4):258–64.Google Scholar
  34. 34.
    Kalyankar P, Panzade P, Lahoti S. Formulation design and optimization of orodispersible tablets of quetiapine fumarate by sublimation method. Indian J Pharm Sci. 2015;77(3):267–73.CrossRefGoogle Scholar
  35. 35.
    Ibahim TM, Abdallah MH, El-Megrab NA, et al. Upgrading of dissolution and anti-hypertensive effect of carvedilol via two combined approaches: self-emulsification and liquisolid techniques. Drug Dev Ind Pharm. 2018;44(6):873–85.CrossRefGoogle Scholar
  36. 36.
    Terakita A, Byrn SR. Structure and physical stability of hydrates and thermotropic mesophase of calcium benzoate. J Pharm Sci. 2006;95(5):1162–72.CrossRefGoogle Scholar
  37. 37.
    Filho ROC, Franco PIBM, Conceição EC, Leles MIG. Stability studies on nifedipine tablets using thermogravimetry and differential scanning calorimetry. J Therm Anal Calorim. 2009;97:343–7.CrossRefGoogle Scholar
  38. 38.
    Shete G, Puri V, Kumar L, Bansal AK. Solid state characterization of commercial crystalline and amorphous atorvastatin calcium samples. AAPS PharmSciTech. 2010;11(2):598–609.CrossRefGoogle Scholar
  39. 39.
    Alakayleh F, Rashid I, Al-Omari MMH, et al. Compression profiles of different molecular weight. Powder Technol. 2016;299:107–18.CrossRefGoogle Scholar
  40. 40.
    Persson AS, Ahmed H, Velaga S, Alderborn G. Powder compression properties of paracetamol, paracetamol hydrochloride, paracetamol cocrystals and coformers. J Pharm Sci. 2018;107(7):1920–7.CrossRefGoogle Scholar
  41. 41.
    Paul S, Sun CC. Dependence of friability on tablet mechanical properties and a predictive approach for binary mixtures. Pharm Res. 2017;34:2901–9.CrossRefGoogle Scholar
  42. 42.
    Shivanand P, Sprockel OL. Compaction behaviour of cellulose polymers. Powder Technol. 1992;69:177–84.CrossRefGoogle Scholar
  43. 43.
    Nordström J, Klevan I, Alderborn G. A protocol for the classification of powder compression characteristics. Eur J Pharm Biopharm. 2012;80(1):209–16.CrossRefGoogle Scholar
  44. 44.
    Krycer I, Pope DG, Hersey JA. An evaluation of the techniques employed to investigate powder compaction behaviour. Int J Pharm. 1982;12:113–34.CrossRefGoogle Scholar
  45. 45.
    Heckel RW. Density-pressure relationship in powder compaction. Trans Metall Soc AIME. 1961;221:671–5.Google Scholar
  46. 46.
    Heckel RW. An analysis of powder compaction phenomena. Trans Metall Soc AIME. 1961;221:1001–8.Google Scholar
  47. 47.
    Chowhan ZT, Chow YP. Compression behaviour of pharmaceutical powders. Int J Pharm. 1980;5:139–48.CrossRefGoogle Scholar
  48. 48.
    Andhariya JV, Choi S, Wang Y, Zou Y, Burgess DJ, Shen J. Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres. Int J Pharm. 2017;520(1–2):79–85.CrossRefGoogle Scholar
  49. 49.
    Gryczke A, Schminke S, Maniruzzaman M, Beck J, Douroumis D. Development and evaluation of orally disintegrating tablets (ODTs) containing ibuprofen granules prepared by hot melt extrusion. Colloid Surface Biointer. 2011;86:275–84.CrossRefGoogle Scholar
  50. 50.
    Indian Pharmacopoeia, 2007. Volume 2. Government of India Ministry of Health & Family Welfare Ghaziabad: The Indian Pharmacopoeia Commission pp 751–52.Google Scholar
  51. 51.
    Kumar L, Reddy MS, Verma R, et al. Selection of cryoprotective agent for freeze drying of valsartan solid lipid nanoparticles. Lat Am J Pharm. 2016;35:483–9.Google Scholar
  52. 52.
    Silverstein RM, Webster FX. Infrared Spectroscopy. Spectrometric identification of organic compounds. 6th Ed. Singapore: John Wiley & Sons (Asia) Pte. Ltd. 2005;71–143.Google Scholar
  53. 53.
    Hu L, Gu D, Hu Q, Shi Y, Gao N. Investigation of solid dispersion of atorvastatin calcium in polyethylene glycol 6000 and polyvinylpyrrolidone. Trop J Pharm Res. 2014;13(6):835–42.CrossRefGoogle Scholar
  54. 54.
    Mohylyuk V, Davtian L. Effect of diluent types and soluble diluents particle size on the dissolution profile of trimetazidine dihydrochloride and caffeine from kollidon SR matrix tablets. Int J Pharm Tech Res. 2015;8(6):147–55.Google Scholar
  55. 55.
    Khan MS, Vishakante GD, Bathool A. Preparation and evaluation of sodium alginate porous dosage form as carriers for low dosed active pharmaceutical ingredients. Turk J Pharm Sci. 2012;9(2):183–98.Google Scholar
  56. 56.
    Patil BS, Rao NGR. Formulation and evaluation of fast dissolving tablets of granisetron hydrochloride by vacuum drying technique. Applied Pharm Sci. 2011;1(4):83–8.Google Scholar
  57. 57.
    Harshitha MS, Krishnan SK, Ahmed MG. Formulation and evaluation of fast dissolving tablets of nebivolol hydrochloride. Int J Appl Pharm Biolog Res. 2016;1(2):78–86.Google Scholar
  58. 58.
    Elkordy AA, Tan XN, Essa EA. Spironolactone release from liquisolid formulations prepared with Capryol™ 90, Solutol® HS-15 and Kollicoat® SR 30 D as non-volatile liquid vehicles. Eur J Pharm Biopharm. 2013;83(2):203–23.CrossRefGoogle Scholar
  59. 59.
    Atorvastatin Tablets, Indian Pharmacopoeia. Government of India Ministry of Health & Family Welfare. 2nd ed. The Indian Pharmacopoeia Commission: Ghaziabad; 2007. p. 751.Google Scholar
  60. 60.
    Roberts RJ, Rowe RC. The compaction of pharmaceutical and other materials—a pragmatic approach. Chem Eng Sci. 1987;42(4):903–11.CrossRefGoogle Scholar
  61. 61.
    Atorvastatin calcium trihydrate. European Pharmacopoeia. 8th Edition. Council of Europe. pp. 1598–1600. Available from: https://wenku.baidu.com/view/35a9708f9ec3d5bbfd0a74f3.html?re=view. Accessed on 3rd May 2019.
  62. 62.
    Atorvastatin calcium trihydrate. PubChem. NIH US National Library of Medicine. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/67019418. Accessed on 3rd May 2019.
  63. 63.
    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.CrossRefGoogle Scholar
  64. 64.
    Pathan IB, Shingare PR, Kurumkar P. Formulation design and optimization of novel mouth dissolving tablets for venlafaxine hydrochloride using sublimation technique. J Pharm Res. 2013;6:593–8.Google Scholar
  65. 65.
    Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on biopharmaceutics classification system – Guidance for Industry, U.S. Department of health and human services. Food and Drug Administration (FDA), Centre for Drug Evaluation and Research (CDER), December 2017. Available from: https://www.fda.gov/downloads/Drugs/Guidances/ucm070246.pdf. Accessed on 20th June 2018.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Shikha Y. Singh
    • 1
  • Salwa
    • 1
  • Rupesh K. Shirodkar
    • 2
  • Ruchi Verma
    • 3
  • Lalit Kumar
    • 1
    Email author
  1. 1.Department of Pharmaceutics, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationUdupiIndia
  2. 2.Department of PharmaceuticsGoa College of PharmacyPanajiIndia
  3. 3.Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationUdupiIndia

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