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Enhancement of docetaxel solubility using binary and ternary solid dispersion systems.
Drug Dev Ind Pharm. 2015; 41(11):1847-55.DD

Abstract

CONTEXT

Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery.

OBJECTIVE

This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique.

METHOD

DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).

RESULTS AND DISCUSSION

Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93 ± 11.01 µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9 ± 0.2 µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization.

CONCLUSION

Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.

Authors+Show Affiliations

a International Medical University , Kuala Lumpur , Malaysia and.a International Medical University , Kuala Lumpur , Malaysia and.a International Medical University , Kuala Lumpur , Malaysia and.b Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia , Adelaide , SA , Australia.a International Medical University , Kuala Lumpur , Malaysia and.b Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia , Adelaide , SA , Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25721984

Citation

Lim, Sue May, et al. "Enhancement of Docetaxel Solubility Using Binary and Ternary Solid Dispersion Systems." Drug Development and Industrial Pharmacy, vol. 41, no. 11, 2015, pp. 1847-55.
Lim SM, Pang ZW, Tan HY, et al. Enhancement of docetaxel solubility using binary and ternary solid dispersion systems. Drug Dev Ind Pharm. 2015;41(11):1847-55.
Lim, S. M., Pang, Z. W., Tan, H. Y., Shaikh, M., Adinarayana, G., & Garg, S. (2015). Enhancement of docetaxel solubility using binary and ternary solid dispersion systems. Drug Development and Industrial Pharmacy, 41(11), 1847-55. https://doi.org/10.3109/03639045.2015.1014818
Lim SM, et al. Enhancement of Docetaxel Solubility Using Binary and Ternary Solid Dispersion Systems. Drug Dev Ind Pharm. 2015;41(11):1847-55. PubMed PMID: 25721984.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of docetaxel solubility using binary and ternary solid dispersion systems. AU - Lim,Sue May, AU - Pang,Zyu Wenn, AU - Tan,Hwei Yuin, AU - Shaikh,Mohsin, AU - Adinarayana,Gorajana, AU - Garg,Sanjay, Y1 - 2015/09/04/ PY - 2015/2/28/entrez PY - 2015/2/28/pubmed PY - 2016/7/28/medline KW - Anti-cancer KW - Soluplus KW - apparent solubility KW - freeze-drying KW - solubility parameter SP - 1847 EP - 55 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 41 IS - 11 N2 - CONTEXT: Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery. OBJECTIVE: This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique. METHOD: DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). RESULTS AND DISCUSSION: Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93 ± 11.01 µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9 ± 0.2 µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization. CONCLUSION: Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/25721984/Enhancement_of_docetaxel_solubility_using_binary_and_ternary_solid_dispersion_systems_ L2 - https://www.tandfonline.com/doi/full/10.3109/03639045.2015.1014818 DB - PRIME DP - Unbound Medicine ER -