Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability
Abstract
The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin((R)) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin((R)) UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant... increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.
Keywords:
carbamazepine / dissolution rate / PAMPA test / solid dispersions / S-SMEDDS / S-SNEDDS / characterizationSource:
Molecules, 2015, 20, 8, 14684-14698Publisher:
- MDPI, Basel
Funding / projects:
DOI: 10.3390/molecules200814684
ISSN: 1420-3049
PubMed: 26287134
WoS: 000361375400071
Scopus: 2-s2.0-84941249098
Collections
Institution/Community
PharmacyTY - JOUR AU - Krstić, Marko AU - Popović, Miljana AU - Dobričić, Vladimir AU - Ibrić, Svetlana PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2405 AB - The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin((R)) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin((R)) UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine. PB - MDPI, Basel T2 - Molecules T1 - Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability VL - 20 IS - 8 SP - 14684 EP - 14698 DO - 10.3390/molecules200814684 ER -
@article{ author = "Krstić, Marko and Popović, Miljana and Dobričić, Vladimir and Ibrić, Svetlana", year = "2015", abstract = "The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin((R)) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin((R)) UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.", publisher = "MDPI, Basel", journal = "Molecules", title = "Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability", volume = "20", number = "8", pages = "14684-14698", doi = "10.3390/molecules200814684" }
Krstić, M., Popović, M., Dobričić, V.,& Ibrić, S.. (2015). Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability. in Molecules MDPI, Basel., 20(8), 14684-14698. https://doi.org/10.3390/molecules200814684
Krstić M, Popović M, Dobričić V, Ibrić S. Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability. in Molecules. 2015;20(8):14684-14698. doi:10.3390/molecules200814684 .
Krstić, Marko, Popović, Miljana, Dobričić, Vladimir, Ibrić, Svetlana, "Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability" in Molecules, 20, no. 8 (2015):14684-14698, https://doi.org/10.3390/molecules200814684 . .