AAPS PharmSci

, Volume 3, Issue 2, pp 57–68 | Cite as

Study of crystallization of endogenous surfactant in Eudragit NE30D-Free films and its influence on drug-release properties of controlled-release diphenhydramine HCI pellets coated with Eudragit NE30D

  • Angela Y. LinEmail author
  • Larry L. Augsburger
  • Nouman A. Muhammad
  • David Pope


This study investigates the crystallization of the endogenous surfactant nonoxynol 100 in Eudragit NE30D-free films during storage and the influences of nonoxynol 100 on the dissolution of diphenhydramine hydrochloric acid (HCL) pellets coated with Eudragit NE30D before and after aging at ambient conditions. Polarizing light microscopy showed that when Eudragit NE30D-free films were stored at ambient conditions, off-white, flower-shaped crystals formed and increased in the polymer film as storage time increased. Also, x-ray diffraction showed polymer crystals in the aged free film. Thermogravimetric analysis showed no evidence of combined volatile molecules with the polymer molecules, and Fourier transformed infrared spectroscopy (FTIR) data suggested the same chemical composition of the polymer before and after phase separation. Further, from normal light microscopy, the appearance of the melting droplets in the polymer film indicated that the polymer molecules did not form the crystals. After the extraction of nonoxynol 100 by water, the free film formed by the water-extracted Eudragit NE30D was found free of the crystals after aging at the same conditions. The combination of the thermogravimetric analysis, FTIR, and microscopy showed that the origin of the crystals in dry Eudragit NE30D-free films came from nonoxynol 100, and not from the polymer molecules themselves. Monitoring by differential scanning calorimeter, it was found that the rates of crystallization of nonoxynol 100 were faster when the films were stored at 30°C and 40°C than when stored at ambient conditions and 45°C. When stored at −5°C, the crystallization rate was nearly zero. As the temperature got closer to melting temperature, the crystallization rate was very low because the system was in a thermodynamically disfavored state. The rate gradually increased and finally passed through a maximum as the crystallization temperature decreased. As the temperature kept decreasing, the crystallization rate became small again and eventually stopped because the system turned into a kinetically disfavored state. Because the phase transition of nonoxynol 100 in Eudragit NE30D occurred at ambient conditions, its influence on the dissolution of diphenhydramine HCL pellets coated with Eudragit NE30D was studied. Three different levels of nonoxynol 100 were used in Eudragit NE30D dispersions to make 3 different batches of Eudragit NE30D film-coated, controlled-release diphenhydramine HCL pellets. The results showed the dissolution rate increased as the level of nonoxynol 100 increased in the coating formula. Compared to the commonly used water-soluble additive human peripheral mononuclear cell, nonoxynol 100 was more effective in enhancing the dissolution of diphenhydramine HCL from pellets coated with Eudragit NE30D. Further study showed that the phase separation of the surfactant during aging tends to stabilize or slightly increase dissolution rates at higher surfactant levels.

Key words

Eudragit NE30D Endogenous Surfactant Free Film Diphenhydramine HCL Pellets 


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  1. 1.
    Sinko CM, Yee AF, Amidon GL. Prediction of physical aging controlled-release coatings: the application of the relaxation coupling model to glassy cellulose acetate. Pharm Res. 1991;8(6):698–705.PubMedCrossRefGoogle Scholar
  2. 2.
    Guo JH, Robertson RE, Amidon GL. Influence of physical aging on mechanical properties of polymer free films: the prediction of long-term aging effects on the water permeability and dissolution rate of polymer film-coated tablets. Pharm Res. 1991;8(12):1500–1504.PubMedCrossRefGoogle Scholar
  3. 3.
    Herman J, Visavarungroj N, Remon JP. Instability of drug release from anhydrous theophylline-microcrystalline cellulose formulations. Int J Pharm. 1989;55:143–146.CrossRefGoogle Scholar
  4. 4.
    Gutierrez-Rocca JC, McGinity JW. Intluence of ageing on the physical-mechanical properties of acrylic resin films cast from aqueous dispersions and organic solutions. Drug Dev Ind Pharm. 1993;19:315–332.CrossRefGoogle Scholar
  5. 5.
    Amighi K, Moes AJ. Influence of curing conditions on the drug release rate from Eudragit NE30D film coated sustained-release theophylline pellets. S.T.P. PHARMA SCIENCES 1997;7(2):141–147.Google Scholar
  6. 6.
    Ghebre-Sellassie I, Gordon RH, Nesbitt RU, Fawzi MB. Evaluation of acrylic-based modified-release film coatings. Int J Pharm 1987;37:211–218.CrossRefGoogle Scholar
  7. 7.
    Robertson RE. Effect of free-volume fluctuations on polymer relaxation in the glassy state. J Polym Sci Polym Symp. 1978;63:173–183.CrossRefGoogle Scholar
  8. 8.
    Bodmeier R, Paeratakul O. Propranolol HCL release from acrylic films prepared from aqueous latexes. Int J Pharm. 1990;59:197–203.CrossRefGoogle Scholar
  9. 9.
    Gopferich A, Lee G. The influence of endogenous surfactant on the structure and drug-release properties of Eudragit NE30D-matrices. J Control Rel. 1992;18:133–144.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  • Angela Y. Lin
    • 1
    Email author
  • Larry L. Augsburger
    • 1
  • Nouman A. Muhammad
    • 2
  • David Pope
    • 2
  1. 1.School of Pharmacy, Department of Pharmaceutical SciencesUniversity of MarylandBaltimore
  2. 2.Pfizer Global Research and DevelopmentMorris Plains

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