Skip to main content
SpringerLink
Log in

Influence of different viscosity grade Methocel and Ethocel polymers for the development of controlled release dimenhydrinate matrix tablets

  • Original Paper
  • Published:
Polymer Bulletin Aims and scope Submit manuscript

Abstract

Dimenhydrinate is a therapeutic agent used for the treatment of nausea and vomiting. A conventional dose of dimenhydrinate is 50 mg per 8 h. Once-daily controlled release tablets of dimenhydrinate were formulated intended to treat emesis. The tablets were formulated using hydrophilic polymers Methocel® and hydrophobic polymers Ethocel® and subsequently analyzed for pre-compression and post-compression characteristics, % moisture uptake, dissolution profiles and release behavior of the drug. Identification of active ingredient and compatibility of blends were analyzed through FT-IR. Drug release kinetics of dimenhydrinate was assessed at pH 1.2, 4.5 and 6.8. The results of release profiles were evaluated for different kinetic models including model dependent and model independent. The optimized formulation K100M 30% showed ideal pre-compression properties and in vitro characteristics. Tablets exhibited a controlled drug release pattern due to the formation of a viscous gel layer followed by erosion. Furthermore, zero-order best described the release pattern with the value of r2 ˃ 0.99. Once-daily tablets released 98–100% drug in 24 h. Significantly more concentration and higher viscosity grade of hydrophilic polymer ensured the required pattern of drug release.

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

Similar content being viewed by others

References

  1. Del Cuvillo A, Mullol J, Bartra J, Davila I, Jauregui I, Montoro J, Sastre J, Valero A (2006) Comparative pharmacology of the H1 antihistamines. J Investig Allergol Clin Immunol 16(1):3–12

    PubMed  Google Scholar 

  2. Lerner E, Flashner-Barak M, v Achthoven E, Keegstra H, Smit R (2006) Delayed release formulations of 6-mercaptopurine. US Patent, US 20060008520A1

  3. Hutton J, Morris J (1992) Long-acting carbidopa-levodopa in the management of moderate and advanced Parkinson's disease. Neurology 42(1 Suppl 1):51–56 discussion 57-60

    CAS  PubMed  Google Scholar 

  4. Wagstaff AJ, Goa KL (2001) Once-weekly fluoxetine. Drugs 61(15):2221–2228

    Article  CAS  Google Scholar 

  5. Perrie Y, Rades T (2009) Pharmaceutics: drug delivery and targeting. Pharmaceutical Press, PA

    Google Scholar 

  6. Aulton ME, Taylor KM (2017) Aulton's pharmaceutics e-book: the design and manufacture of medicines. Elsevier Health Sciences, Amsterdam

    Google Scholar 

  7. Nokhodchi A, Raja S, Patel P, Asare-Addo K (2012) The role of oral controlled release matrix tablets in drug delivery systems. Bioimpacts 2(4):175–187. https://doi.org/10.5681/bi.2012.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Moore JW (1996) Mathematical comparison of dissolution profiles. Pharm Technol 20:64–75

    Google Scholar 

  9. O'hara T, Dunne A, Butler J, Devane J, Group ICW (1998) A review of methods used to compare dissolution profile data. Pharm Sci Technol Today 1(5):214–223

    Article  CAS  Google Scholar 

  10. Shah VP, Tsong Y, Sathe P, Liu J-P (1998) In vitro dissolution profile comparison—statistics and analysis of the similarity factor, f2. Pharm Res 15(6):889–896

    Article  CAS  Google Scholar 

  11. Siewert M, Dressman J, Brown CK, Shah VP, Aiache J-M, Aoyagi N, Bashaw D, Brown C, Brown W, Burgess D (2003) FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. Aaps Pharmscitech 4(1):43–52

    Article  CAS  Google Scholar 

  12. FDA U (1997) Guidance for industry: dissolution testing of immediate-release solid oral dosage forms. Food and Drug Administration Center for Drug Evaluation and Research (CDER), USA

    Google Scholar 

  13. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie S (2010) DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 12(3):263–271. https://doi.org/10.1208/s12248-010-9185-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Patra C, Kumar A, Pandit H, Singh S, Devi M (2007) Design and evaluation of sustained release bilayer tablets of propranolol hydrochloride. Acta Pharm 57(4):479–489

    Article  CAS  Google Scholar 

  15. The United States Pharmacopeia (2012) USP 35/The National Formulary, NF 30. US Pharmacopeial Convention, Rockville, MD

  16. Commission BP (2016) British Pharmacopoeia 2017. Stationery Office, London

    Google Scholar 

  17. Ghayas S, Shoaib MH, Qazi F, Bushra R, Ali FR, Maboos M, Khalid F (2019) Influence of different viscosity grade cellulose-based polymers on the development of valsartan controlled release tablets. Polym Bull. https://doi.org/10.1007/s00289-019-02802-2

    Article  Google Scholar 

  18. Costa P, Lobo JMS (2001) Modeling and comparison of dissolution profiles. Eur J Pharm Sci 13(2):123–133

    Article  CAS  Google Scholar 

  19. Grdešič P, Vrečer F, Ilić I (2016) Flow and compaction properties of hypromellose: new directly compressible versus the established grades. Drug Dev Ind Pharm 42(11):1877–1886

    Article  Google Scholar 

  20. Mehsud SU, Khan GM, Hussain A, Akram M, Akhlaq M, Khan KA, Shakoor A (2016) Controlled release matrix tablets of glipizide: influence of different grades of ethocel and Co-excipient on drug release. Pak J Pharm Sci 29(3):779–787

    PubMed  Google Scholar 

  21. Hussain T, Saeed T, Mumtaz AM, Javaid Z, Abbas K, Awais A, Idrees HA (2013) Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets. ACTA Poloniae Pharm-Drug Res 70:749–757

    CAS  Google Scholar 

  22. Grund J, Koerber M, Walther M, Bodmeier R (2014) The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets. Int J Pharm 469(1):94–101

    Article  CAS  Google Scholar 

  23. Shah RB, Tawakkul MA, Khan MA (2008) Comparative evaluation of flow for pharmaceutical powders and granules. Aaps Pharmscitech 9(1):250–258

    Article  CAS  Google Scholar 

  24. Mathur V, Nagpal K, Singh SK, Mishra DN (2013) Comparative release profile of sustained release matrix tablets of verapamil HCl. Int J Pharm Investig 3(1):60

    Article  CAS  Google Scholar 

  25. Wadher K, Kakde R, Umekar M (2011) Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers. Indian J Pharm Sci 73(2):208

    Article  CAS  Google Scholar 

  26. Sun CC, Hou H, Gao P, Ma C, Medina C, Alvarez FJ (2009) Development of a high drug load tablet formulation based on assessment of powder manufacturability: moving towards quality by design. J Pharm Sci 98(1):239–247

    Article  CAS  Google Scholar 

  27. Patel P, Dave A, Vasava A, Patel P (2015) Formulation and characterization of sustained release dosage form of moisture sensitive drug. Int J pharm Investig 5(2):92

    Article  CAS  Google Scholar 

  28. Ochoa L, Igartua M, Hernandez R, Gascon A, Pedraz J (2005) Preparation of sustained release hydrophilic matrices by melt granulation in a high-shear mixer. J Pharm Pharm Sci a Publ Canadian Soc Pharm Sci, Societe canadienne des sciences pharmaceutiques 8(2):132–140

    CAS  Google Scholar 

  29. Raghuvanshi S, Pathak K (2014) Recent advances in delivery systems and therapeutics of cinnarizine: a poorly water soluble drug with absorption window in stomach. J Drug Deliv 2014:479246

    Article  Google Scholar 

  30. Wang Z, Shmeis RA (2006) Dissolution controlled drug delivery systems Design of controlled release drug delivery systems. McGraw-Hill, United States, pp 139–172

    Google Scholar 

  31. Klančar U, Horvat M, Baumgartner S (2012) Correlating cellulose derivative intrinsic viscosity with mechanical susceptibility of swollen hydrophilic matrix tablets. AAPS PharmSciTech 13(3):903–910

    Article  Google Scholar 

  32. Klančar U, Markun B, Baumgartner S, Legen I (2013) A novel beads-based dissolution method for the in vitro evaluation of extended release HPMC matrix tablets and the correlation with the in vivo data. AAPS journal 15(1):267–277

    Article  Google Scholar 

  33. Klančar U, Baumgartner S, Legen I, Smrdel P, Kampuš NJ, Krajcar D, Markun B, Kočevar K (2015) Determining the polymer threshold amount for achieving robust drug release from HPMC and HPC matrix tablets containing a high-dose BCS class I model drug: in vitro and in vivo studies. AAPS PharmSciTech 16(2):398–406

    Article  Google Scholar 

  34. Li CL, Martini LG, Ford JL, Roberts M (2005) The use of hypromellose in oral drug delivery. J Pharm Pharmacol 57(5):533–546

    Article  CAS  Google Scholar 

  35. Mallipeddi R (2009) The application of coarse particle ethyl cellulose and high molecular weight polyethylene oxide in the production of beads by extrusion-spheronization. University of the Sciences in Philadelphia, Pennsylvania

    Google Scholar 

  36. Tsong Y, Hammerstrom T, Sathe P, Shah VP (1996) Statistical assessment of mean differences between two dissolution data sets. Drug Inf J 30(4):1105–1112

    Article  Google Scholar 

  37. Zhang H, Surian JM (2010) Biopharmaceutic consideration and assessment for oral controlled release formulations Oral Controlled Release Formulation Design and Drug Delivery Theory to Practice. Wiley, New Jersey, pp 33–45

    Book  Google Scholar 

  38. Ritger PL, Peppas NA (1987) A simple equation for description of solute release I Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Controlled Release 5(1):23–36

    Article  CAS  Google Scholar 

  39. Bae Y (2010) Drug delivery systems using polymer nanoassemblies for cancer treatment. Ther deliv 1(3):361–363

    Article  CAS  Google Scholar 

  40. Fotaki N, Aivaliotis A, Butler J, Dressman J, Fischbach M, Hempenstall J, Klein S, Reppas C (2009) A comparative study of different release apparatus in generating in vitro–in vivo correlations for extended release formulations. Eur J Pharm Biopharm 73(1):115–120

    Article  CAS  Google Scholar 

  41. Kostewicz ES, Abrahamsson B, Brewster M, Brouwers J, Butler J, Carlert S, Dickinson PA, Dressman J, Holm R, Klein S (2014) In vitro models for the prediction of in vivo performance of oral dosage forms. Eur J Pharm Sci 57:342–366

    Article  CAS  Google Scholar 

  42. Shoaib MH, Siddiqi SAS, Yousuf RI, Zaheer K, Hanif M, Rehana S, Jabeen S (2010) Development and evaluation of hydrophilic colloid matrix of famotidine tablets. Aaps Pharmscitech 11(2):708–718

    Article  CAS  Google Scholar 

  43. Yuksel N, Kanık AE, Baykara T (2000) Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and-independent methods. Int J Pharm 209(1–2):57–67

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Zeb-un-Nisa

    Present address: Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan

Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan

    Zeb-un-Nisa, Muhammad Harris Shoaib, Rabia Ismail Yousuf, Zafar Alam Mahmood, Sabahat Jabeen & Faaiza Qazi

  2. Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan

    Syed Imran Ali

Authors
  1. Zeb-un-Nisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhammad Harris Shoaib
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rabia Ismail Yousuf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Syed Imran Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zafar Alam Mahmood
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sabahat Jabeen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Faaiza Qazi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Harris Shoaib.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeb-un-Nisa, Shoaib, M.H., Yousuf, R.I. et al. Influence of different viscosity grade Methocel and Ethocel polymers for the development of controlled release dimenhydrinate matrix tablets. Polym. Bull. 78, 5525–5546 (2021). https://doi.org/10.1007/s00289-020-03369-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00289-020-03369-z

Keywords

Search

Navigation