Journal of Pharmaceutical Investigation

, Volume 48, Issue 3, pp 313–321 | Cite as

New blends of hydroxypropylmethylcellulose and Gelucire 44/14: physical property and controlled release of drugs with different solubility

  • Kyung-Ho Lee
  • Chulhun Park
  • Giwon Oh
  • Jun-Bom Park
  • Beom-Jin Lee
Original Article


New blends of hydroxypropylmethylcellulose (HPMC, 4000 cps) and Gelucire®44/14 (GE) were utilized to modulate the solubility and release rate of poorly water-soluble drug in a controlled manner. HPMC was used as sustained release polymer while GE was blended as a solubilizing carrier. The binary blends of HPMC and GE with proportional ratios (0, 25, 50, 70, 100%) were prepared by three different preparation methods: simple physical mixing, solvent evaporation and hot-melting. The physical properties such as surface morphology, thermal behavior and crystallinity pattern of the binary blends without loading drugs were then characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), respectively. Finally, the ternary solid dispersions (SD) were prepared by dispersing model drugs in a binary blend. Two model drugs, water-soluble acetaminophen (AAP) and poorly water-soluble pranlukast (PLK) were applied to the binary blends. In case of AAP, HPMC retarded release rate but GE had no significant solubilizing effect due to the high AAP solubility, In contrast, the release rate of PLK was efficiently modulated release rate in a controlled manner with an aid of HPMC and GE. Surely, GE could play a key role in enhancing the dissolution rate while HPMC efficiently controlled release rate of drugs without losing drug crystallinity.


Binary blends Hydroxypropylmethylcellulose Gelucire®44/14 Physical characterization Enhanced dissolution Controlled release Poorly water-soluble drug 



This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning (2013M3A9B5075841), The Republic of Korea. The authors declare that there is no conflict of interest regarding the publication of this paper.


  1. Acevedo A, Takhistov P, de la Rosa CP, Florián V (2014) Thermal gelation of aqueous hydroxypropylmethylcellulose solutions with SDS and hydrophobic drug particles. Carbohydr Polym 102:74–79CrossRefPubMedGoogle Scholar
  2. Brough C, Williams RO 3rd (2013) Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int J Pharm 453:157–166CrossRefPubMedGoogle Scholar
  3. Cao QR, Choi YW, Cui JH, Lee B-J (2005) Formulation, release characteristics and bioavailability of novel monolithic hydroxypropylmethylcellulose matrix tablets containing acetaminophen. J Control Release 108:351–361CrossRefPubMedGoogle Scholar
  4. Cao QR, Choi JS, Liu Y, Xu WJ, Yang M, Lee B-J, Cui JH (2013) A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation. Drug Dev Ind Pharm 39:1720–1730CrossRefPubMedGoogle Scholar
  5. Chono S, Takeda E, Seki T, Morimoto K (2008) Enhancement of the dissolution rate and gastrointestinal absorption of pranlukast as a model poorly water-soluble drug by grinding with gelatin. Int J Pharm 347:71–78CrossRefPubMedGoogle Scholar
  6. da Fonseca Antunes AB, De Geest BG, Vervaet C, Remon JP (2013) Gelucire 44/14 based immediate release formulations for poorly water-soluble drugs. Drug Dev Ind Pharm 39:791–798CrossRefGoogle Scholar
  7. De Robertis S, Bonferoni MC, Elviri L, Sandri G, Caramella C, Bettini R (2015) Advances in oral controlled drug delivery: the role of drug-polymer and interpolymer non-covalent interactions. Expert Opin Drug Deliv 12:441–453CrossRefPubMedGoogle Scholar
  8. El-Badry M, Fetih G, Fathy M (2009) Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000. Saudi Pharm J 17:217–225CrossRefPubMedPubMedCentralGoogle Scholar
  9. Faisal W, Ruane-O’Hora T, O’Driscoll CM, Griffin BT (2013) A novel lipid-based solid dispersion for enhancing oral bioavailability of Lycopene–In vivo evaluation using a pig model. Int J Pharm 453:307–314CrossRefPubMedGoogle Scholar
  10. Fernandez S, Chevrier S, Ritter N, Mahler B, Demarne F, Carrière F, Jannin V (2009) In vitro gastrointestinal lipolysis of four formulations of piroxicam and cinnarizine with the self emulsifying excipients Labrasol® and Gelucire® 44/14. Pharm res 26:1901–1910CrossRefPubMedGoogle Scholar
  11. Grohganz H, Priemel PA, Lobmann K, Nielsen LH, Laitinen R, Mullertz A, Van den Mooter G, Rades T (2014) Refining stability and dissolution rate of amorphous drug formulations. Expert Opin Drug Deliv 11:977–989CrossRefPubMedGoogle Scholar
  12. 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 469:94–101CrossRefPubMedGoogle Scholar
  13. Huang Y, Dai WG (2014) Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B 4:18–25CrossRefPubMedGoogle Scholar
  14. Jain AK, Soderlind E, Viriden A, Schug B, Abrahamsson B, Knopke C, Tajarobi F, Blume H, Anschutz M, Welinder A, Richardson S, Nagel S, Abrahmsen-Alami S, Weitschies W (2014) The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets. J Control Release 187:50–58CrossRefPubMedGoogle Scholar
  15. Jang SW, Choi YW, Kang MJ (2014) Preparation of solid dispersion of Everolimus in Gelucire 50/13 using melt granulation technique for enhanced drug release. Bull Korean Chem Soc 35:1939CrossRefGoogle Scholar
  16. Jannin V (2009) Lauroyl polyoxylglycerides, functionalized coconut oil, enhancing the bioavailability of poorly soluble active substances. Ol Corps Gras Lipides 16:267–272CrossRefGoogle Scholar
  17. Kalantzi L, Reppas C, Dressman JB, Amidon GL, Junginger HE, Midha KK, Shah VP, Stavchansky SA, Barends DM (2006) Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol). J Pharm Sci 95:4–14CrossRefPubMedGoogle Scholar
  18. Laitinen R, Lobmann K, Strachan CJ, Grohganz H, Rades T (2013) Emerging trends in the stabilization of amorphous drugs. Int J Pharm 453:65–79CrossRefPubMedGoogle Scholar
  19. Meena A, Parikh T, Gupta SS, Serajuddin AT (2014) Investigation of thermal and viscoelastic properties of polymers relevant to hot melt extrusion, II: cellulosic polymers. J Excip Food Chem 5:46–55Google Scholar
  20. Mistry P, Mohapatra S, Gopinath T, Vogt FG, Suryanarayanan R (2015) Role of the strength of drug-polymer interactions on the molecular mobility and crystallization inhibition in ketoconazole solid dispersions. Mol Pharm 12:3339–3350CrossRefPubMedGoogle Scholar
  21. Park JB, Lim J, Kang CY, Lee B-J (2013) Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: distribution of atoms and carrier and texture analysis. Curr Drug Deliv 10:732–741CrossRefPubMedGoogle Scholar
  22. Park JB, Park YJ, Kang CY, Lee B-J (2015) Modulation of microenvironmental pH and utilization of alkalizers in crystalline solid dispersion for enhanced solubility and stability of clarithromicin. Arch Pharm Res 38:839–848CrossRefPubMedGoogle Scholar
  23. Paudel A, Worku ZA, Meeus J, Guns S, Van den Mooter G (2013) Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. Int J Pharm 453:253–284CrossRefPubMedGoogle Scholar
  24. Piao Z-Z, Choe J-S, Oh KT, Rhee Y-S, Lee B-J (2014) Formulation and in vivo human bioavailability of dissolving tablets containing a self-nanoemulsifying itraconazole solid dispersion without precipitation in simulated gastrointestinal fluid. Eur J Pharm Sci 51:67–74CrossRefPubMedGoogle Scholar
  25. Sarode AL, Wang P, Obara S, Worthen DR (2014) Supersaturation, nucleation, and crystal growth during single- and biphasic dissolution of amorphous solid dispersions: polymer effects and implications for oral bioavailability enhancement of poorly water soluble drugs. Eur J Pharm Biopharm 86:351–360CrossRefPubMedGoogle Scholar
  26. Shaw LR, Irwin WJ, Grattan TJ, Conway BR (2005) The effect of selected water-soluble excipients on the dissolution of paracetamol and Ibuprofen. Drug Dev Ind Pharm 31:515–525CrossRefPubMedGoogle Scholar
  27. Shimpi SL, Chauhan B, Mahadik K, Paradkar A (2005) Stabilization and improved in vivo performance of amorphous etoricoxib using Gelucire 50/13. Pharm Res 22:1727–1734CrossRefPubMedGoogle Scholar
  28. Sutananta W, Craig DQ, Newton JM (1994) An investigation into the effect of preparation conditions on the structure and mechanical properties of pharmaceutical glyceride bases. Int J Pharm 110:75–91CrossRefGoogle Scholar
  29. Svensson A, Neves C, Cabane B (2004) Hydration of an amphiphilic excipient, Gelucire® 44/14. Int J Pharm 281:107–118CrossRefPubMedGoogle Scholar
  30. Tran TT-D, Tran PH-L (2013) Investigation of polyethylene oxide-based prolonged release solid dispersion containing isradipine. J Drug Deliv Sci Technol 23:269–274CrossRefGoogle Scholar
  31. Tran T-H, Park C, Kang T, Park Y-J, Oh E, Lee B-J (2015) Micromeritic properties and instrumental analysis of physical mixtures and solid dispersions with adsorbent containing losartan: comparison of dissolution-differentiating factors. Powder Technol 272:269–275CrossRefGoogle Scholar
  32. Van Nguyen H, Park C, Oh E, Lee B-J (2016a) Improving the dissolution rate of a poorly water-soluble drug via adsorption onto pharmaceutical diluents. J Drug Deliv Sci Technol 35:146–154CrossRefGoogle Scholar
  33. Van Nguyen H, Nguyen VH, Lee B-J (2016b) Dual release and molecular mechanism of bilayered aceclofenac tablet using polymer mixture. Int J Pharm 515:233–244CrossRefPubMedGoogle Scholar
  34. Vo CL, Park C, Lee B-J (2013) Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm 85:799–813CrossRefPubMedGoogle Scholar
  35. Wang L, Hao Y, Liu N, Ma M, Yin Z, Zhang X (2012) Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method. Drug Dev Ind Pharm 38:1381–1389CrossRefPubMedGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2017

Authors and Affiliations

  • Kyung-Ho Lee
    • 1
  • Chulhun Park
    • 1
  • Giwon Oh
    • 1
  • Jun-Bom Park
    • 2
  • Beom-Jin Lee
    • 1
    • 3
  1. 1.College of PharmacyAjou UniversitySuwonRepublic of Korea
  2. 2.College of PharmacySahmyook UniversitySeoulSouth Korea
  3. 3.Institute of Pharmaceutical Science and TechnologyAjou UniversitySuwonRepublic of Korea

Personalised recommendations