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Solubility enhancement of desloratadine by solid dispersion in poloxamers.
Int J Pharm. 2012 Oct 15; 436(1-2):161-70.IJ

Abstract

The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X(1) - type of poloxamer in SD and X(2) - poloxamer ratio in SD) and one process variable (X(3) - compression force) on the drug dissolution rate. It was found that desloratadine in SDs existed in the amorphous state, and that can be largely responsible for the enhanced intrinsic solubility, which was more pronounced in SDs containing poloxamer 188. Statistical analysis of the factorial design revealed that both investigated formulation variables exert a significant effect on the drug dissolution rate. Increased poloxamer ratio in SDs resulted in increased drug dissolution rate, with poloxamer 188 contributing to a faster dissolution rate than poloxamer 407, in accordance with the results of intrinsic dissolution tests. Moreover, there is a significant interaction between poloxamer ratio in SD and compression force. Higher poloxamer ratio in SDs and higher compression force results in a significant decrease of the drug dissolution rate, which can be attributed to the lower porosity of the tablets and more pronounced bonding between poloxamer particles.

Authors+Show Affiliations

Galenika a.d., Batajnički drum bb., 11080 Belgrade, Serbia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22772487

Citation

Kolašinac, Nemanja, et al. "Solubility Enhancement of Desloratadine By Solid Dispersion in Poloxamers." International Journal of Pharmaceutics, vol. 436, no. 1-2, 2012, pp. 161-70.
Kolašinac N, Kachrimanis K, Homšek I, et al. Solubility enhancement of desloratadine by solid dispersion in poloxamers. Int J Pharm. 2012;436(1-2):161-70.
Kolašinac, N., Kachrimanis, K., Homšek, I., Grujić, B., Ðurić, Z., & Ibrić, S. (2012). Solubility enhancement of desloratadine by solid dispersion in poloxamers. International Journal of Pharmaceutics, 436(1-2), 161-70. https://doi.org/10.1016/j.ijpharm.2012.06.060
Kolašinac N, et al. Solubility Enhancement of Desloratadine By Solid Dispersion in Poloxamers. Int J Pharm. 2012 Oct 15;436(1-2):161-70. PubMed PMID: 22772487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Solubility enhancement of desloratadine by solid dispersion in poloxamers. AU - Kolašinac,Nemanja, AU - Kachrimanis,Kyriakos, AU - Homšek,Irena, AU - Grujić,Branka, AU - Ðurić,Zorica, AU - Ibrić,Svetlana, Y1 - 2012/07/06/ PY - 2011/12/12/received PY - 2012/06/11/revised PY - 2012/06/30/accepted PY - 2012/7/10/entrez PY - 2012/7/10/pubmed PY - 2013/1/17/medline SP - 161 EP - 70 JF - International journal of pharmaceutics JO - Int J Pharm VL - 436 IS - 1-2 N2 - The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X(1) - type of poloxamer in SD and X(2) - poloxamer ratio in SD) and one process variable (X(3) - compression force) on the drug dissolution rate. It was found that desloratadine in SDs existed in the amorphous state, and that can be largely responsible for the enhanced intrinsic solubility, which was more pronounced in SDs containing poloxamer 188. Statistical analysis of the factorial design revealed that both investigated formulation variables exert a significant effect on the drug dissolution rate. Increased poloxamer ratio in SDs resulted in increased drug dissolution rate, with poloxamer 188 contributing to a faster dissolution rate than poloxamer 407, in accordance with the results of intrinsic dissolution tests. Moreover, there is a significant interaction between poloxamer ratio in SD and compression force. Higher poloxamer ratio in SDs and higher compression force results in a significant decrease of the drug dissolution rate, which can be attributed to the lower porosity of the tablets and more pronounced bonding between poloxamer particles. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/22772487/Solubility_enhancement_of_desloratadine_by_solid_dispersion_in_poloxamers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(12)00659-X DB - PRIME DP - Unbound Medicine ER -