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Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes.
AAPS PharmSciTech. 2009; 10(1):81-7.AP

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 beta-cyclodextrin (beta-CD), hydroxypropyl beta-CD (HPbetaCD), and randomly methylated beta-CD (RMbetaCD) 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 A(L)-type solubility diagram for beta-CD and A(P)-type solubility diagram for HPbetaCD and RMbetaCD. The phase solubility data enabled calculating stability constants (K (s)) for EFV-betaCD, EFV-HPbetaCD, and EFV-RMbetaCD 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 HPbetaCD and RMbetaCD inclusion complexes prepared by the freeze drying method. Thus, complexation with HPbetaCD and RMbetaCD could possibly improve the dissolution rate-limited absorption of EFV.

Authors+Show Affiliations

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19148759

Citation

Sathigari, Sateeshkumar, et al. "Physicochemical Characterization of Efavirenz-cyclodextrin Inclusion Complexes." AAPS PharmSciTech, vol. 10, no. 1, 2009, pp. 81-7.
Sathigari S, Chadha G, Lee YH, et al. Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes. AAPS PharmSciTech. 2009;10(1):81-7.
Sathigari, S., Chadha, G., Lee, Y. H., Wright, N., Parsons, D. L., Rangari, V. K., Fasina, O., & Babu, R. J. (2009). Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes. AAPS PharmSciTech, 10(1), 81-7. https://doi.org/10.1208/s12249-008-9180-3
Sathigari S, et al. Physicochemical Characterization of Efavirenz-cyclodextrin Inclusion Complexes. AAPS PharmSciTech. 2009;10(1):81-7. PubMed PMID: 19148759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes. AU - Sathigari,Sateeshkumar, AU - Chadha,Gurkishan, AU - Lee,Y-H Phillip, AU - Wright,Nydeia, AU - Parsons,Daniel L, AU - Rangari,Vijay K, AU - Fasina,Oladiran, AU - Babu,R Jayachandra, Y1 - 2009/01/16/ PY - 2008/09/18/received PY - 2008/12/15/accepted PY - 2009/1/17/entrez PY - 2009/1/17/pubmed PY - 2009/6/24/medline SP - 81 EP - 7 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 10 IS - 1 N2 - 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 beta-cyclodextrin (beta-CD), hydroxypropyl beta-CD (HPbetaCD), and randomly methylated beta-CD (RMbetaCD) 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 A(L)-type solubility diagram for beta-CD and A(P)-type solubility diagram for HPbetaCD and RMbetaCD. The phase solubility data enabled calculating stability constants (K (s)) for EFV-betaCD, EFV-HPbetaCD, and EFV-RMbetaCD 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 HPbetaCD and RMbetaCD inclusion complexes prepared by the freeze drying method. Thus, complexation with HPbetaCD and RMbetaCD could possibly improve the dissolution rate-limited absorption of EFV. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/19148759/Physicochemical_characterization_of_efavirenz_cyclodextrin_inclusion_complexes_ L2 - https://dx.doi.org/10.1208/s12249-008-9180-3 DB - PRIME DP - Unbound Medicine ER -