AAPS PharmSciTech

, Volume 10, Issue 1, pp 81–87

Physicochemical Characterization of Efavirenz–Cyclodextrin Inclusion Complexes

  • Sateeshkumar Sathigari
  • Gurkishan Chadha
  • Y-H. Phillip Lee
  • Nydeia Wright
  • Daniel L. Parsons
  • Vijay K. Rangari
  • Oladiran Fasina
  • R. Jayachandra Babu
Research Article

DOI: 10.1208/s12249-008-9180-3

Cite this article as:
Sathigari, S., Chadha, G., Lee, YH.P. et al. AAPS PharmSciTech (2009) 10: 81. doi:10.1208/s12249-008-9180-3

Abstract

Efavirenz (EFV) is an oral antihuman immunodeficiency virus type 1 drug with extremely poor aqueous solubility. Thus, its gastrointestinal absorption is limited by the dissolution rate of the drug. The objective of this study was to characterize the inclusion complexes of EFV with β-cyclodextrin (β-CD), hydroxypropyl β-CD (HPβCD), and randomly methylated β-CD (RMβCD) to improve the solubility and dissolution of EFV. The inclusion complexation of EFV with cyclodextrins in the liquid state was characterized by phase solubility studies. The solid-state characterization of various EFV and CD systems was performed by X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy analyses. Dissolution studies were carried out in distilled water using US Pharmacopeia dissolution rate testing equipment. Phase solubility studies provided an AL-type solubility diagram for β-CD and AP-type solubility diagram for HPβCD and RMβCD. The phase solubility data enabled calculating stability constants (Ks) for EFV-βCD, EFV-HPβCD, and EFV-RMβCD systems which were 288, 469, and 1,073 M−1, respectively. The physical and kneaded mixtures of EFV with CDs generally provided higher dissolution of EFV as expected. The dissolution of EFV was substantially higher with HPβCD and RMβCD inclusion complexes prepared by the freeze drying method. Thus, complexation with HPβCD and RMβCD could possibly improve the dissolution rate-limited absorption of EFV.

Key words

cyclodextrins dissolution rate efavirenz inclusion complexes solubility 

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Sateeshkumar Sathigari
    • 1
  • Gurkishan Chadha
    • 1
  • Y-H. Phillip Lee
    • 1
  • Nydeia Wright
    • 2
  • Daniel L. Parsons
    • 1
  • Vijay K. Rangari
    • 2
  • Oladiran Fasina
    • 3
  • R. Jayachandra Babu
    • 1
  1. 1.Department of Pharmacal Sciences, Harrison School of PharmacyAuburn UniversityAuburnUSA
  2. 2.Center for Advanced Materials (T-COM)Tuskegee UniversityTuskegeeUSA
  3. 3.Biosystems EngineeringAuburn UniversityAuburnUSA

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