Skip to main content
SpringerLink
Log in

Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique

  • Research Article
  • Published:
Journal of Pharmaceutical Innovation Aims and scope Submit manuscript

Abstract

The purpose of the present investigation is to emphasize the application of hot-melt extrusion technique (HMET) for the preparation of sustained release matrix formulation of highly dosed, freely soluble drugs. In this study, sustained release multiple unit dosage of venlafaxine hydrochloride (VH) was prepared by HMET. Custom design was used to screen the effect of four factors-type of polymer (ethylcellulose and eudragit RSPO) (X 1), amount of polymer (X 2), type of plasticizer (DBS, ATBC, TEC, and PEG) (X 3), and plasticizer concentration (X 4), on the drug release at 8 h (Y1) and machine torque (Y2). The experiments were carried out according to a four-factor 16-run statistical model and subjected to 12-h dissolution study in purified water. The significance of the model was indicated by ANOVA. Results of in vitro release study indicate that formulations prepared with higher amount of ethylcellulose and DBC show significant retardation at 8 h. The result shows that increase in concentration of polymer with the combination of water insoluble plasticizer (DBS and ATBC) has better sustained release while increasing concentration of TEC and PEG results faster in vitro release. Besides that increase in plasticizer concentration helps in reducing the melt temperature and machine torque. The in vivo study was performed, and formulations were compared using area under the plasma concentration-time curve (AUC0-∞), time to reach peak plasma concentration (Tmax), and peak plasma concentration (Cmax). The drug release profiles of extrudes were found to fit both diffusion and surface erosion models. Further to this, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction analysis of the hot-melt extrudates demonstrated that VH remained crystalline and was homogeneously dispersed throughout the polymer matrix.

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
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54:107–17.

    CAS  PubMed  Google Scholar 

  2. Crowley MM, Zhang F, Repka MA, Thumma S, Upadhye SB, Battu SK. Pharmaceutical applications of hot-melt extrusion: Part I. Drug Dev Ind Pharm. 2007;33:909–26.

    Article  CAS  PubMed  Google Scholar 

  3. Albers J, Alles R, Matthée K, Knop K, Nahrup JS, Kleinebudde P. Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion. Eur J Pharm Biopharm. 2009;71:387–94.

    CAS  PubMed  Google Scholar 

  4. Brabander C, Vervaet C, Remon JP. Development and evaluation of sustained release mini-matrices prepared via hot melt extrusion. J Control Release. 2003;89:235–47.

    Article  PubMed  Google Scholar 

  5. Özgüney I, Shuwisitkul D, Bodmeier R. Development and characterization of extended release Kollidon® SR mini-matrices prepared by hot-melt extrusion. Eur J Pharm Biopharm. 2009;73:140–5.

    PubMed  Google Scholar 

  6. Verhoeven E, Vervaet C, Remon JP. Xanthan gum to tailor drug release of sustained-release ethylcellulose mini-matrices prepared via hot-melt extrusion: In vitro and in vivo evaluation. Eur J Pharm Biopharm. 2006;63:320–30.

    CAS  PubMed  Google Scholar 

  7. Mehuys E, Remon JP, Vervaet C. Production of enteric capsules by means of hot-melt extrusion. Eur J Pharm Biopharm. 2005;24:207–12.

    CAS  Google Scholar 

  8. Mehuys E, Vervaet C, Gielen I, Van Bree H, Remon JP. In vitro and in vivo evaluation of a matrix-in-cylinder system for sustained drug delivery. J Control Release. 2004;96:261–71.

    Article  CAS  PubMed  Google Scholar 

  9. Mehuys E, Vervaet C, Remon JP. Hot-melt extruded ethylcellulose cylinders containing a HPMC-Gelucire® core for sustained drug delivery. J Control Release. 2004;94:273–80.

    Article  CAS  PubMed  Google Scholar 

  10. Andrews GP, Jones DS, Diak OA, McCoy CP, Watts AB, McGinity JW. The manufacture and characterisation of hot-melt extruded enteric tablets. Eur J Pharm Biopharm. 2008;69:264–73.

    CAS  PubMed  Google Scholar 

  11. Yang R, Wang Y, Zheng X, Meng J, Tang X, Zhang X. Preparation and evaluation of ketoprofen hot-melt extruded enteric and sustained-release tablets. Drug Dev Ind Pharm. 2008;34:83–9.

    Article  CAS  PubMed  Google Scholar 

  12. Bruce LD, Shah NH, Waseem MA, Infeld MH, McGinity JW. Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid. Eur J Pharm Biopharm. 2005;59:85–97.

    CAS  PubMed  Google Scholar 

  13. Repka MA, McGinity JW. Bioadhesive properties of hydroxypropylcellulose topical films produced by hot-melt extrusion. J Control Release. 2001;70:341–51.

    Article  CAS  PubMed  Google Scholar 

  14. Repka MA, McGinity JW. Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion. Pharm Dev Technol. 2001;6:297.

    Article  CAS  PubMed  Google Scholar 

  15. Ghalanbor Z, Körber M, Bodmeier R. Improved lysozyme stability and release properties of poly (lactide-co-glycolide) implants prepared by hot-melt extrusion. Pharma Res. 2010;27:371–9.

    Article  CAS  Google Scholar 

  16. Gosau M, Müller B. Release of gentamycin sulphate from biodegradable PLGA-implants produced by hot melt extrusion. Die Pharm. 2010;65:487–92.

    CAS  Google Scholar 

  17. Hülsmann S, Backensfeld T, Keitel S, Bodmeier R. Melt extrusion—an alternative method for enhancing the dissolution rate of 17 [beta]-estradiol hemihydrate. Eur J Pharm Biopharm. 2000;49:237–42.

    PubMed  Google Scholar 

  18. Rambali B, Verreck G, Baert L, Massart DL. Itraconazole formulation studies of the melt-extrusion process with mixture design. Drug Dev Ind Pharm. 2003;29:641–52.

    Article  CAS  PubMed  Google Scholar 

  19. Chokshi R, Zia H. Hot-melt extrusion technique: a review. Iran J Pharm Res. 2004;3:3–16.

    Google Scholar 

  20. Shaikh NA, Abidi SE. LH block, evaluation of ethylcellulose matrix for prolonged release formulations: I. Water soluble drugs: Acetaminophen and theophylline. Drug Dev Ind Pharm. 1987;13:1345–69.

    Article  CAS  Google Scholar 

  21. Follonier N, Doelker E, Cole ET. Evaluation of hot-melt extrusion as a new technique for the production of polymer based pellets for sustained release capsules containing high loadings of freely soluble drugs. Drug Dev Ind Pharm. 1994;20:1323–39.

    Article  CAS  Google Scholar 

  22. Schwartz JB, O’Connor RE. Optimization techniques in pharmaceutical formulation and processing. In: Banker GS, Rhodes CT, editors. Modern pharmaceutics. 3rd ed. New York: Marcel Dekker; 1997. p. 727–52.

    Google Scholar 

  23. Lee S, Kim MS, Jun SW, Park J-S, Hwang SJ. Preparation and controlled release spheronized beads by a simple extrusion and modified spheronization process. Arch Pharm Res. 2005;28:619–25.

    Article  CAS  PubMed  Google Scholar 

  24. Seo SM, Lee HS, Lee J, Lee HY, Lee B, Lee HB, et al. Controlled release of tamsulosin from nanopore-forming granules. J Kor Pharm Sci. 2006;36:39–44.

    CAS  Google Scholar 

  25. Harrington Jr EC. The desirability function. Ind Qual Control. 1995;21:494–8.

    Google Scholar 

Download references

Acknowledgments

The authors wish to thank ThermoFisher Scientific India and BASF Chemical Company, Mumbai, India for helping in melt extrusion trial.

Author information

Authors and Affiliations

  1. School of Pharmacy & Medical Science, Singhania University, Pacheri Bari, Jhunjhunu, Rajasthan, India

    Ravindra Tiwari

  2. Dr. Reddy’s Lab. Ltd, Hyderabad, India

    Sunil Kumar Agarwal

  3. I.S.F. College of Pharmacy, Moga, Punjab, India

    R. S. R. Murthy

  4. Govt. Girls College, Sector −14, Girgaon, Haryana, India

    Shweta Tiwari

Authors
  1. Ravindra Tiwari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sunil Kumar Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. S. R. Murthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shweta Tiwari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ravindra Tiwari.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tiwari, R., Agarwal, S.K., Murthy, R.S.R. et al. Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique. J Pharm Innov 9, 246–258 (2014). https://doi.org/10.1007/s12247-014-9191-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12247-014-9191-4

Keywords

Search

Navigation