Skip to main content

Optimization of film-coating formulation containing a novel low molecular weight hypromellose to achieve balanced tablet-coating performance

Abstract

In recent years, a novel low molecular weight hypromellose (hypromellose 2906, VLV hypromellose) was developed to improve tablet-coating process and lower costs in the pharmaceutical industry. Such VLV hypromellose imparted economic, environmental, and performance benefits to the coating process and final products. However, there were still some concerns about this polymer in regard to weak mechanical strength of films and resultant stability issues of film coatings on tablets. In this study, a tablet-coating formulation was optimized using Box–Behnken design via blending conventional hypromellose with VLV hypromellose to achieve balanced coating performance in terms of highly productive coating, no sticking issues under mild coating conditions, and robust tablet film coatings in an accelerated stability study. By addition of only 5 wt% of conventional hypromellose (3.35 wt% HPMC E50 and 1.65 wt% HPMC E3), the film elongation and toughness index of optimized VLV hypromellose formulation increased by 154% and 372%, respectively, while the solution viscosity was still suitable for spray coating. The results of the following tablet-coating trials and stability study revealed that the stability and quality of tablet film coatings were significantly improved using this optimized VLV hypromellose-coating formulation, while a highly productive coating process and mild coating conditions without “sticking” issues were maintained simultaneously to the utmost extent.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. Cole, C, Hogan, J, Aulton, M, Pharmaceutical Coating Technology. Taylor & Francis, London, 1995

    Book  Google Scholar 

  2. Warnke, G, Pharmaceutical Coatings, Ullmann’s Encyclopedia of Industrial Chemistry, Vol. 26. Wiley Online, New York, 2012

    Google Scholar 

  3. Gaur, PK, Mishra, S, Gautam, R, Singh, AP, Yasir, M, “Film Coating Technology: Past, Present and Future.” J. Pharm. Sci. Pharmacol., 1 57–67 (2014)

    Article  Google Scholar 

  4. Felton, LA, “Mechanisms of Polymeric Film Formation.” Int. J. Pharm., 457 423–427 (2013)

    Article  Google Scholar 

  5. Sharma, PH, Kalasare, SN, Kamble, RA, “Review on Polymers Used for Film Coating.” Asian J. Pharm. Technol. Innov., 1 (2) 01–16 (2013)

    Google Scholar 

  6. Augsburger, LL, Hoag, SW, Pharmaceutical Dosage Forms: Tablets, 3rd ed. Taylor & Francis, London, 2008

    Book  Google Scholar 

  7. Hsu, ER, Gebert, MS, Becker, NT, Gaertner, AL, “The Effects of Plasticizers and Titanium Dioxide on the Properties of Poly (Vinyl Alcohol) Coatings.” Pharm. Dev. Technol., 6 (2) 277–284 (2001)

    Article  Google Scholar 

  8. Rogers, TL, Sheskey, PJ, Furukawa, H, Mallon, CB, Trampe, M, Holbrook, DL, “Investigation of a Novel Hypromellose Polymer for High Productivity Tablet Coating Applications.” Annual meeting and exposition of the American Association of Pharmaceutical Scientists, 2008

  9. Rogers, TL, Holbrook, DL, Coppens, KA, Schmitt, RL, “Cellulose Ether Coating Composition and Method.” US Patent 0275814, 2010

  10. Mallon, CB, “Method for Preparing Very Low Viscosity Cellulose Ether and Product.” US Patent, 0307379, 2010

  11. Chemistry of METHOCEL™ Cellulose Ether—A Technical Review, Technical Bulletin of Dow Pharma and Food Solution, 2013

  12. Khot, S, Hwang, J, Anderson, J, Coppens, K, Sheskey, PJ, “How Very-Low-Viscosity Coatings Reduce the Total Cost of Ownership of Coating Operations.” Tablet & Capsules, July, 4–9, 2012

  13. Lu, ZJ, Wang, C, Chen, F, He, YJ, Gao, H, “Effect of METHOCEL™ VLV on Quality Improvement of Coating Preparation Loaded with Heat- and Moisture-Sensitive Drugs.” Chin. J. Pharm., 46 (9) 82–86 (2015)

    Google Scholar 

  14. Wong, PM, “A Study on the Side-Spray Fluidized Bed Processor with Swirling Airflow for Granulation and Drug Layering.” A Thesis Submitted for the Degree of Ph.D., National University of Singapore, 2013

  15. Rowe, RC, Forse, SF, “The Effect of Polymer Molecular Weight on the Incidence of Film Cracking and Splitting on Film Coated Tablets.” J. Pharm. Pharmacol., 32 (1) 583–584 (1980)

    Article  Google Scholar 

  16. Bruce, HF, Sheskey, PJ, Garcia-Todd, P, Felton, LA, “Novel Low-Molecular-Weight Hypromellose Polymeric Films for Aqueous Film Coating Applications.” Drug Dev. Ind. Pharm., 37 (12) 1439–1445 (2011)

    Article  Google Scholar 

  17. Sheskey, PJ, “VLV Hypromellose Coating Stability Study: Summary of 0 (Initial), 1, 3 and 6 Month Data.” Unpublished data, 2011

  18. Okutgen, E, Hogan, JE, Aulton, ME, “Quantitative Estimation of Internal Stress Development in Aqueous HPMC Tablet Film Coats.” Int. J. Pharm., 119 193–202 (1995)

    Article  Google Scholar 

  19. Mancha, Z, Wiley, C, Sheskey, PJ, Felton, LA, “Mechanical Properties of Very Low Viscosity Hypromellose Films Blended with Conventional Hypromellose Polymers.” Annual meeting and exposition of the American Association of Pharmaceutical Scientists, 2011

  20. METHOCEL™ Cellulose Ethers-Technical Handbook, Dow Pharma and Food Solutions, 2002

  21. ASTM D882-02: Standard Test Method for Tensile Properties of Thin Plastic Sheeting, American Society of Testing Materials, 2002

  22. Pashley, EL, Zhang, Y, Lockwood, PE, Rueggeberg, FA, Pashley, DH, “Effects of HEMA on Water Evaporation from Water–HEMA Mixtures.” Dent. Mater., 14 6–10 (1998)

    Article  Google Scholar 

  23. ICH Harmonized Tripartite Guideline: Stability Testing of New Drug Substances and Products Q1A (R2), International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use, 2003

  24. Standard Operation Procedure for Tablet Friability Test, China Pharmacopeia, appendix, 2010

  25. Okhamafe, AO, York, P, “Stress Crack Resistance of Some Pigmented and Unpigmented Tablet Film Coating Systems.” J. Pharm. Pharmacol., 37 449–454 (1985)

    Article  Google Scholar 

  26. Park, HJ, Weller, CL, Vergano, PJ, Testin, RF, “Permeability and Mechanical Properties of Cellulose-Based Edible Films.” J. Food Sci., 58 (6) 1361–1364 (1993)

    Article  Google Scholar 

  27. Keary, CM, “Characterization of METHOCEL Cellulose Ethers by Aqueous SEC with Multiple Detectors.” Carbohydr. Polym., 45 293–303 (2001)

    Article  Google Scholar 

  28. Thomas, GM, Paquita, EM, Thomas, JP, Cellulose Ethers, Encyclopedia of Polymer Science and Technology. Wiley Online, New York, 2002

    Google Scholar 

  29. Rowe, RC, “The Molecular Weight and Molecular Weight Distribution of Hydroxypropyl Methylcellulose Used in the Film Coating of Tablets.” J. Pharm. Pharmacol., 32 116–119 (1980)

    Article  Google Scholar 

  30. Brandy, JE, Durig, T, Shang, SS, Polymer Property and Characterization, Developing Oral Solid Dosage Form: Pharmaceutical Theory and Practice. Elsevier Inc., Amsterdam, 2009

    Google Scholar 

  31. Kennedy, MA, Peacock, AJ, Mandelkern, L, “Tensile Properties of Crystalline Polymers: Linear Polyethylene.” Macromolecules, 27 5297–5310 (1994)

    Article  Google Scholar 

  32. Kennedy, MA, Peacock, AJ, Failla, MD, Lucas, JC, Mandelkern, L, “Tensile Properties of Crystalline Polymers: Random Copolymers of Ethylene.” Macromolecules, 28 1407–1421 (1995)

    Article  Google Scholar 

  33. Lazaridou, A, Biliaderis, CG, Kontogiorgos, V, “Molecular Weight Effects on Solution Rheology of Pullulan and Mechanical Properties of Its Films.” Carbohydr. Polym., 52 151–166 (2003)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hao Gao.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gao, H., Wang, C. & He, Y. Optimization of film-coating formulation containing a novel low molecular weight hypromellose to achieve balanced tablet-coating performance. J Coat Technol Res 14, 1159–1167 (2017). https://doi.org/10.1007/s11998-016-9908-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11998-016-9908-z

Keywords

  • VLV hypromellose
  • Tablet coating
  • Box–Behnken design
  • Toughness index