Tags

Type your tag names separated by a space and hit enter

Gefitinib-cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies.
Drug Dev Ind Pharm. 2009 Sep; 35(9):1113-20.DD

Abstract

BACKGROUND

Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs).

METHODS

Phase solubility studies of gefitinib with hydroxypropyl betaCD (HPbetaCD) and randomly methylated betaCD (RMbetaCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC).

RESULTS

Gefitinib formed stable complexes with HPbetaCD and RMbetaCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M(-1) for HPbetaCD and RMbetaCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A(N) type of phase-solubility diagrams, whereas gefitinib and HPbetaCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A(P)-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPbetaCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC.

CONCLUSION

Gefitinib formed stable inclusion complexes with HPbetaCD and RMbetaCD, and the solubility and dissolution rate of the drug was significantly increased.

Authors+Show Affiliations

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

19640249

Citation

Phillip Lee, Y-H, et al. "Gefitinib-cyclodextrin Inclusion Complexes: Physico-chemical Characterization and Dissolution Studies." Drug Development and Industrial Pharmacy, vol. 35, no. 9, 2009, pp. 1113-20.
Phillip Lee YH, Sathigari S, Jean Lin YJ, et al. Gefitinib-cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies. Drug Dev Ind Pharm. 2009;35(9):1113-20.
Phillip Lee, Y. H., Sathigari, S., Jean Lin, Y. J., Ravis, W. R., Chadha, G., Parsons, D. L., Rangari, V. K., Wright, N., & Babu, R. J. (2009). Gefitinib-cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies. Drug Development and Industrial Pharmacy, 35(9), 1113-20. https://doi.org/10.1080/03639040902783074
Phillip Lee YH, et al. Gefitinib-cyclodextrin Inclusion Complexes: Physico-chemical Characterization and Dissolution Studies. Drug Dev Ind Pharm. 2009;35(9):1113-20. PubMed PMID: 19640249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gefitinib-cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies. AU - Phillip Lee,Y-H, AU - Sathigari,Sateesh, AU - Jean Lin,Y-J, AU - Ravis,William R, AU - Chadha,Gurkishan, AU - Parsons,Daniel L, AU - Rangari,Vijay K, AU - Wright,Nydeia, AU - Babu,R Jayachandra, PY - 2009/7/31/entrez PY - 2009/7/31/pubmed PY - 2010/1/6/medline SP - 1113 EP - 20 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 35 IS - 9 N2 - BACKGROUND: Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs). METHODS: Phase solubility studies of gefitinib with hydroxypropyl betaCD (HPbetaCD) and randomly methylated betaCD (RMbetaCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC). RESULTS: Gefitinib formed stable complexes with HPbetaCD and RMbetaCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M(-1) for HPbetaCD and RMbetaCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A(N) type of phase-solubility diagrams, whereas gefitinib and HPbetaCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A(P)-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPbetaCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC. CONCLUSION: Gefitinib formed stable inclusion complexes with HPbetaCD and RMbetaCD, and the solubility and dissolution rate of the drug was significantly increased. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/19640249/Gefitinib_cyclodextrin_inclusion_complexes:_physico_chemical_characterization_and_dissolution_studies_ L2 - https://www.tandfonline.com/doi/full/10.1080/03639040902783074 DB - PRIME DP - Unbound Medicine ER -