Advertisement

AAPS PharmSciTech

, Volume 19, Issue 3, pp 1358–1366 | Cite as

Micronized Zaleplon Delivery via Orodispersible Film and Orodispersible Tablets

  • Prashanth Manda
  • Carmen Popescu
  • Abhishek Juluri
  • Karthik Janga
  • Praneeth Rao Kakulamarri
  • Sushmitha Narishetty
  • S. Narasimha Murthy
  • Michael A. Repka
Research Article

Abstract

The following research study focuses on improving the solubility of zaleplon (BCS class II drug) via micronization technique in order to enhance its oral delivery in orodispersible formulations. Zaleplon along with a surfactant solution was micronized by ultrasonication. The micronization process reduced the particle size of the crystalline drug about six-fold from its original size of 155.5 μm. The micronized zalepon dispersion was lyophilized to allow for a change in the state of matter (to a powder). The superior dissolution parameters (Q5, Q30, IDR, MDR, MDT, DE, and RDR) of zaleplon in microcrystalline form over the original crystalline form in in vitro dissolution studies had unraveled that micronization technique is an efficient tool in enhancing drug solubility. The micronized zaleplon solid dispersion (after lyophilization) was loaded into orodispersible tablet (ODT) and orodispersible film (ODF) formulations. The positive quality of ODT with adequate hardness and smooth texture was attributing to the presence of Pearlitol Flash® as a ready to use ODT platform. On the other hand, the ODF loaded with micronized zaleplon and prepared with Lycoat® RS 720 (as a film former) ensured adequate tensile strength. The disintegration time of ODT and ODF was 30 ± 5 and 35 ± 5 s, respectively. Thus, the orodispersible formulations containing micronized zaleplon have a strong potential for rapid disintegration following superior absorption in solution state through oral cavity into the blood stream, envisaging better oral delivery.

KEY WORDS

Micronization Zaleplon Lyophilization Orodispersible films Orodispersible tablet Lycoat® RS 720 Neosorb® P60W Pearlitol Flash® 

Abbreviations

BCS

biopharmaceutics classification system

Q5

cumulative drug release in 5 min

Q30

cumulative drug release in 30 min

DE

dissolution efficiency

MDT

mean dissolution time (minutes)

MDR

mean dissolution rate

IDR

initial dissolution rate

RDR

relative dissolution rate to pure drug

MZLP

micronized zaleplon lyophilized powder

FTIR

Fourier transform infrared

PXRD

powder X-ray diffractometry

References

  1. 1.
    Qiu L, Sautter J, Liu Y, Age GD. Gender differences in linkages of sleep with subsequent mortality and health among very old Chinese. Sleep Med. 2011;12(10):1008–17.  https://doi.org/10.1016/j.sleep.2011.04.014.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Foley D, Ancoli-Israel S, Britz P, Walsh J. Sleep disturbances and chronic disease in older adults: results of the 2003 National Sleep Foundation Sleep in America Survey. J Psychosom Res. 2004;56(5):497–502.  https://doi.org/10.1016/j.jpsychores.2004.02.010.CrossRefPubMedGoogle Scholar
  3. 3.
    Foley DJ, Monjan AA, Brown SL, Simonsick EM, Wallace RB, Blazer DG. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18(6):425–32.  https://doi.org/10.1093/sleep/18.6.425.CrossRefPubMedGoogle Scholar
  4. 4.
    Leblanc MF, Desjardins S, Desgagné A. The relationship between sleep habits, anxiety, and depression in the elderly. Nat. Sci. Sleep. 2015;7:33–42.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Bankar MA, Chaudhari SK, Chaudhari KD. Impact of long term yoga practice on sleep quality and quality of life in the elderly. J Ayurveda Integr Med. 2013;4:28–32.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ancoli-Israel S, Walsh JK, Mangano RM, Fujimori M. Zaleplon, a novel nonbenzodiazepine hypnotic, effectively treats insomnia in elderly patients without causing rebound effects. Prim Care Companion J Clin Psychiatry. 199;1:114–120.Google Scholar
  7. 7.
    Béland SG, Préville M, Dubois MF, Lorrain D, Voyer P, Bossé C, et al. Scientific Committee of the ESA Study. The association between length of benzodiazepine use and sleep quality in older population. Int J Geriatr Psychiatry. 2011;26(9):908–15.  https://doi.org/10.1002/gps.2623.CrossRefPubMedGoogle Scholar
  8. 8.
    Dooley M, Plosker G. Zaleplon a review of its use in the treatment of insomnia. Drugs. 2000;60(2):413–45.  https://doi.org/10.2165/00003495-200060020-00014.CrossRefPubMedGoogle Scholar
  9. 9.
    Waghmare A, Pore Y, Kuchekar B. Development and characterization of zaleplon solid dispersion systems: a technical note. AAPS Pharm Sci Tech. 2008;9(2):536–43.  https://doi.org/10.1208/s12249-008-9077-1.CrossRefGoogle Scholar
  10. 10.
    Drover DR. Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives zaleplon, zolpidem and zopiclone. Clin Pharmacokinet. 2004;43(4):227–38.  https://doi.org/10.2165/00003088-200443040-00002.CrossRefPubMedGoogle Scholar
  11. 11.
    Valleri M, Mura P, Maeshrelli F, Cirri M, Ballerini R. Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique. Drug Dev Ind Pharm. 2004;30:525–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Popescu C, Manda P, Juluri A, Janga KY, Cidda M, Murthy SN. Enhanced dissolution efficiency of zaleplon solid dispersions via modified ß-cyclodextrin molecular inclusion complexes. J Pharma Pharma Sci. 2015;1:1–10.Google Scholar
  13. 13.
    Janga KY, Jukanti R, Velpula A, Sunkavalli S, Bandari S, Kandadi P, et al. Bioavailability enhancement of zaleplon via proliposomes: role of surface charge. Eur J PharmBiopharm. 2012;80(2):347–57.  https://doi.org/10.1016/j.ejpb.2011.10.010.CrossRefGoogle Scholar
  14. 14.
    Gurrapu A, Jukanti R, Bobbala SR, Kanuganti S, Jeevana JB. Improved oral delivery of valsartan from maltodextrin based proniosome powders. Adv Powder Technol. 2012;23(5):583–90.  https://doi.org/10.1016/j.apt.2011.06.005.CrossRefGoogle Scholar
  15. 15.
    Jalay JT. A review on micronization techniques. J. Pharm. Sci Tech. 2011;3:651–81.Google Scholar
  16. 16.
    Rasenack N, Muller BW. Micron-size drug particles: common and novel micronization techniques. Pharm Dev Technol. 2004;9(1):1–13.  https://doi.org/10.1081/PDT-120027417.CrossRefPubMedGoogle Scholar
  17. 17.
    Köllmer M, Popescu C, Manda P, Zhou L, Gemeinhart RA. Stability of benzocaine formulated in commercial oral disintegrating tablet platforms. AAPSPharmSciTech. 2013 Dec;14(4):1333–40.Google Scholar
  18. 18.
    Hoffmann EM, Breitenbach A, Breitkreutz J. Advances in orodispersible films for drug delivery. Expert Opin Drug Delivery. 2011;8:299–316.CrossRefGoogle Scholar
  19. 19.
    Hariharan M, Bogue A. Orally dissolving film strips (ODFS): the final evolution of orally dissolving dosage forms. Drug Delivery Technol. 2009;9:24–9.Google Scholar
  20. 20.
    Chaturvedi A, Srivastava P, Yadav S, Bansal M, Garg G, Sharma PK. Fast dissolving films: a review. Curr Drug Delivery. 2011;8(4):373–80.  https://doi.org/10.2174/156720111795768022.CrossRefGoogle Scholar
  21. 21.
    Arya A, Chandra A, Sharma V, Pathak K. Fast dissolving oral films: an innovative drug delivery system and dosage form. Int J Chem Tech Res. 2010;2:576–83.Google Scholar
  22. 22.
    Jyoti A, Gurpreet S, Seema S, Rana AC. Fast dissolving films: a novel approach to oral drug delivery. Int Res J Pharm. 2011;2:69–74.Google Scholar
  23. 23.
    Malladi M, Jukanti R, Nair N, Wagh S, Padakanti H, Mateti A. Design and evaluation of taste masked dextromethorphan hydrobromide oral disintegrating tablets. Acta Pharma. 2010;60:267–80.CrossRefGoogle Scholar
  24. 24.
    Al-Hamidi H, Edwards AA, Mohammad MA, Nokhodchi A. To enhance dissolution rate of poorly water-soluble drugs: glucosamine hydrochloride as a potential carrier in solid dispersion formulations. Colloids Surf B. 2010;76(1):170–8.  https://doi.org/10.1016/j.colsurfb.2009.10.030.CrossRefGoogle Scholar
  25. 25.
    Valleri M, Mura P, Maeshrelli F, Cirri M, Ballerini R. Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique. Drug Dev Ind Pharm. 2004;30(5):525–34.  https://doi.org/10.1081/DDC-120037483.CrossRefPubMedGoogle Scholar
  26. 26.
    Mishra R, Amin A. Formulation development of taste-masked rapidly dissolving films of cetirizine hydrochloride. Pharm Technol. 2009;33:48–56.Google Scholar
  27. 27.
    Janga KY, Jukanti R, Velpula A, Sunkavalli S, Bandari S, Kandadi P, et al. In situ absorption and bioavailability studies of zaleplon loaded self-nanoemulsifying powders (SNEPs). J Microencapsul. 2013;30:167–72.CrossRefGoogle Scholar
  28. 28.
    Vandana KR, Raju YP, Chowdary VH, Sushma M, Kumar NV. An overview on in situ micronization technique—an emerging novel concept in advanced drug delivery. Saudi Pharm J. 2014;22:283–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Roya T, Varshosaz J, Mostafavi SA, Ali N. Dissolution enhancement of gliclazide using pH change approach in presence of twelve stabilizers with various physico-chemical properties. J Pharm Pharm Sci. 2009;12:250–65.CrossRefGoogle Scholar
  30. 30.
    Hulse WL, Forbes RT, Bonner MC, Getrost M. The characterization and comparison of spray-dried mannitol samples. Drug Dev Ind Pharm. 2009;35(6):712–8.  https://doi.org/10.1080/03639040802516491.CrossRefPubMedGoogle Scholar
  31. 31.
    El-setouhy DA, El-malak NSA. Formulation of novel tianeptine sodium orodispersible film. AAPS Pharm Sci Tech. 2010;11(3):1018–25.  https://doi.org/10.1208/s12249-010-9464-2.CrossRefGoogle Scholar
  32. 32.
    Bruce C, Manning M. Melt extruded thin strips containing coated pharmaceutical. U.S. Patent application 2012030863, December 2012.Google Scholar
  33. 33.
    Jani R, Patel D. Hot melt extrusion: an industrially feasible approach for casting orodispersible film. Asain J Pharma Sci. 2015;10:292–305.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Prashanth Manda
    • 1
    • 2
  • Carmen Popescu
    • 2
  • Abhishek Juluri
    • 1
  • Karthik Janga
    • 3
  • Praneeth Rao Kakulamarri
    • 4
  • Sushmitha Narishetty
    • 5
  • S. Narasimha Murthy
    • 1
  • Michael A. Repka
    • 1
  1. 1.Department of Pharmaceutics and Drug DeliveryThe University of Mississippi, UniversityOxfordUSA
  2. 2.Roquette America Inc.GenevaUSA
  3. 3.Kakatiya Institute of Pharmaceutical SciencesWarangalIndia
  4. 4.Ascent Pharmaceuticals, Centre IslipNew YorkUSA
  5. 5.Kalamazoo CollegeKalamazooUSA

Personalised recommendations