Cellulosic and acrylic polymers based composites for controlled drug release

  • Izza Tariq
  • Abid Mehmood YousafEmail author
  • Syed Atif Raza
  • Yasser Shahzad
  • Talib Hussain
  • Ikram Ullah Khan
  • Tariq Mahmood
  • Muhammad Jamshaid
Original Research


The study focused on the preparation and in vitro characterization of sustained release polymeric systems or solid dispersions for highly water-soluble drugs. Several polymeric composites were fabricated with ethyl cellulose (EC), Eudragit S100 (E-S100) or Eudragit RS100 (E-RS100) in conjunction with hydroxypropyl methylcellulose (HPMC) using 5-fluorouracil (5-FU) as a model drug. The solvent-evaporated composites were evaluated for in vitro release of the drug. In this respect, various mathematical models were applied to assess the release kinetics. Further characterization was accomplished by X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Formulations comprising 5-FU/HPMC/(EC, E-S100 or E-RS100) at the weight ratio of 1/1/3 (formulations III, V and VI) significantly reduced the burst effect in vitro as compared to the plain drug powder. In particular, EC provided better sustained release effect compared with E-S100 and E-RS100 (~ 70% versus 85–87% in 8 h). The effect of higher quantity of EC on drug release was tested with a formulation containing 5-FU/HPMC/EC at the weight ratio of 1/1/4 (formulation IV). The drug was present in the amorphous state of all the above formulations. Thus, these formulations, in particular formulation IV, might be promising delivery systems to circumvent the burst effect caused by highly water-soluble drugs.


Burst effect Cellulosic polymer Eudragit Sustained release solid dispersion Polymeric composite 



The authors are thankful to Rashid Latif College of Pharmacy (Lahore, Pakistan), University of Central Punjab (Lahore, Pakistan) and COMSATS University Islamabad (Lahore Campus, Lahore, Pakistan) for providing materials and laboratory facilities for accomplishing the present research work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Allison SD (2008) Analysis of initial burst in PLGA microparticles. Expert Opin Drug Deliv 5:615–628CrossRefGoogle Scholar
  2. 2.
    Colombo P, Bettini R, Santi P, Peppas NA (2000) Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance. Pharm Sci Technol Today 3:198–204CrossRefGoogle Scholar
  3. 3.
    Yousaf AM, Ramzan M, Shahzad Y, Mahmood T, Jamshaid M (2018) Fabrication and in vitro characterization of fenofibric acid-loaded hyaluronic acid–polyethylene glycol polymeric composites with enhanced drug solubility and dissolution rate. Int J Polym Mater Polym Biomater 68:510–515CrossRefGoogle Scholar
  4. 4.
    Yousaf AM, Malik UR, Shahzad Y, Mahmood T, Hussain T (2019) Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: preparation and in vitro characterization. J Pharm Anal 9:34–39CrossRefGoogle Scholar
  5. 5.
    Chavan RB, Rathi S, Jyothi VGS, Shastri NR (2018) Cellulose based polymers in development of amorphous solid dispersions. Asian J Pharm Sci 14:248–264CrossRefGoogle Scholar
  6. 6.
    Qian F, Huang J, Hussain MA (2010) Drug–polymer solubility and miscibility: stability consideration and practical challenges in amorphous solid dispersion development. J Pharm Sci 99:2941–2947CrossRefGoogle Scholar
  7. 7.
    Huang YT, Tsai TR, Cheng CJ, Cham TM, Lai TF, Chuo WH (2007) Formulation design of a highly hygroscopic drug (pyridostigmine bromide) for its hygroscopic character improvement and investigation of in vitro/in vivo dissolution properties. Drug Dev Ind Pharm 33:403–416CrossRefGoogle Scholar
  8. 8.
    Spireas S (2005) Stabilization of solid drug formulations. US Patent No. 6979462B1Google Scholar
  9. 9.
    Kuksal A, Tiwary AK, Jain NK, Jain S (2006) Formulation and in vitro, in vivo evaluation of extended- release matrix tablet of Zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers. AAPS PharmSciTech 7:E1–E9CrossRefGoogle Scholar
  10. 10.
    Wong V, Kochinke F (1999) Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents.US Patent No.5869079Google Scholar
  11. 11.
    Lee YS, Song JG, Lee SH, Han HK (2017) Sustained-release solid dispersion of pelubiprofen using the blended mixture of aminoclay and pH independent polymers: preparation and in vitro/in vivo characterization. Drug Deliv 24:1731–1739CrossRefGoogle Scholar
  12. 12.
    Siepmann J, Peppas NA (2012) Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev 64:163–174CrossRefGoogle Scholar
  13. 13.
    Kar N, Liu H, Edgar KJ (2011) Synthesis of cellulose adipate derivatives. Biomacromol 12:1106–1115CrossRefGoogle Scholar
  14. 14.
    Ziaee A, Albadarin AB, Padrela L, Faucher A, O’Reilly E, Walker G (2017) Spray drying ternary amorphous solid dispersions of ibuprofen: An investigation into critical formulation and processing parameters. Eur J Pharm Biopharm 120:43–51CrossRefGoogle Scholar
  15. 15.
    Baghel S, Cathcart H, O'Reilly NJ (2016) Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci 105:2527–2544CrossRefGoogle Scholar
  16. 16.
    Kim S, Gupta B, Moon C, Oh E, Jeong JH, Yong CS, Kim JO (2016) Employing an optimized spray-drying process to produce ezetimibe tablets with an improved dissolution profile. J Pharm Investig 46:583–592CrossRefGoogle Scholar
  17. 17.
    Son GH, Lee BJ, Cho CW (2017) Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles. J Pharm Investig 47:287–296CrossRefGoogle Scholar
  18. 18.
    Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15:25–35CrossRefGoogle Scholar
  19. 19.
    Hussain T, Ranjha NM, Shahzad Y (2011) Swelling and controlled release of tramadol hydrochloride from a pH-sensitive hydrogel. Des Monomers Polym 14:233–249CrossRefGoogle Scholar
  20. 20.
    Sohail K, Khan IU, Shahzad Y, Hussain T, Ranjha NM (2014) pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: impact of material parameters on swelling and drug release. Br J Pharm Sci 50:173–184CrossRefGoogle Scholar
  21. 21.
    Khan S, Batchelor H, Hanson P, Saleem IY, Perrie Y, Mohammed AR (2013) Dissolution rate enhancement, in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions. Drug Dev Ind Pharm 39:704–715CrossRefGoogle Scholar
  22. 22.
    Shahzad Y, Saeed S, Ghori MU, Mahmood T, Yousaf AM, Jamshaid M, Sheikh R, Rizvi SA (2018) Influence of polymer ratio and surfactants on controlled drug release from cellulosic microsponges. Int J Biol Macromol 109:963–970CrossRefGoogle Scholar
  23. 23.
    Rao KK, Rao KM, Kumar PN, Chung ID (2010) Novel chitosan-based pH sensitive micro-networks for the controlled release of 5-fluorouracil. Iran Polym J 19:265–276Google Scholar
  24. 24.
    Mahnaj T, Ahmed SU, Plakogiannis FM (2013) Characterization of ethyl cellulose polymer. Pharm Dev Technol 18:982–989CrossRefGoogle Scholar
  25. 25.
    Konno H, Handa T, Alonzo DE, Taylor LS (2008) Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur J Pharm Biopharm 70:493–499CrossRefGoogle Scholar
  26. 26.
    Tanno F, Nishiyama Y, Kokubo H, Obara S (2004) Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions. Drug Dev Ind Pharm 30:9–17CrossRefGoogle Scholar
  27. 27.
    Gupta P, Kakumanu VK, Bansal AK (2004) Stability and solubility of celecoxib-PVP amorphous dispersions: a molecular perspective. Pharm Res 21:1762–1769CrossRefGoogle Scholar
  28. 28.
    Alonzo DE, Raina S, Zhou D, Gao Y, Zhang GGZ, Taylor LS (2012) Characterizing the impact of hydroxypropylmethyl cellulose on the growth and nucleation kinetics of felodipine from supersaturated solutions. Cryst Growth Des 12:1538–1547CrossRefGoogle Scholar
  29. 29.
    Oucherif KA, Raina S, Taylor LS, Litster JD (2013) Quantitative analysis of the inhibitory effect of HPMC on felodipine crystallization kinetics using population balance modeling. CrystEngComm 15:2197–2205CrossRefGoogle Scholar
  30. 30.
    Fan N, He Z, Ma P, Wang X, Li C, Sun J, Sun Y, Li J (2018) Impact of HPMC on inhibiting crystallization and improving permeability of curcumin amorphous solid dispersions. Carbohydr Polym 181:543–550CrossRefGoogle Scholar
  31. 31.
    Wegiel LA, Mosquera-Giraldo LI, Mauer LJ, Edgar KJ, Taylor LS (2015) Phase behavior of resveratrol solid dispersions upon addition to aqueous media. Pharm Res 32:3324–3337CrossRefGoogle Scholar

Copyright information

© Iran Polymer and Petrochemical Institute 2019

Authors and Affiliations

  1. 1.Faculty of PharmacyUniversity of Central PunjabLahorePakistan
  2. 2.Drug Delivery Research Group, Department of PharmacyCOMSATS University Islamabad, Lahore CampusLahorePakistan
  3. 3.Punjab University College of PharmacyUniversity of the PunjabLahorePakistan
  4. 4.Department of Pharmaceutics, Faculty of Pharmaceutical SciencesGovernment College UniversityFaisalabadPakistan

Personalised recommendations