Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability.
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(®) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin(®) 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.
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P.O. Box 146, Belgrade 11221, Serbia. mkrstic109@gmail.com.
Marko
M
Krstić
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P.O. Box 146, Belgrade 11221, Serbia. miljana.popovic17@gmail.com.
Miljana
M
Popović
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P.O. Box 146, Belgrade 11221, Serbia. vladimir@pharmacy.bg.ac.rs.
Vladimir
V
Dobričić
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P.O. Box 146, Belgrade 11221, Serbia. svetlana.ibric@pharmacy.bg.ac.rs.
Svetlana
S
Ibrić
D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry; D008567:Membranes, Artificial; D010316:Particle Size; D010539:Permeability; D011208:Powders; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
D004655:Emulsions; D008567:Membranes, Artificial; D011208:Powders; D013607:Tablets; D014867:Water; D002220:Carbamazepine
PAMPA test; S-SMEDDS; S-SNEDDS; carbamazepine; characterization; dissolution rate; solid dispersions