Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist
Апстракт
One of the problems with orally used drugs is their poor solubility, which can be overcome by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). The aim is to choose the appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol (R) (1: 1)) and cosurfactant (Transcutol (R) HP) are formed by applying mixture design. 16 formulations were formulated, where the proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that desc...ribe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin (R) UFl2, Neusilin (R) FL2, Sylysia (R) 320 and diatomite were used as the carriers. The ratio of SNEDDS: carrier was 1: 1 or 2: 1. Dissolution testing was carried out in the rotation paddles apparatus. Characterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02 +/- 34.09 nm and PdI 0.184 +/- 0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia (R) 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate of carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability.
Извор:
Hemijska industrija, 2016, 70, 5, 525-537Издавач:
- Savez hemijskih inženjera, Beograd
Финансирање / пројекти:
DOI: 10.2298/HEMIND150623059K
ISSN: 0367-598X
WoS: 000388029800005
Scopus: 2-s2.0-84995387463
Институција/група
PharmacyTY - JOUR AU - Krstić, Marko AU - Ibrić, Svetlana PY - 2016 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2618 AB - One of the problems with orally used drugs is their poor solubility, which can be overcome by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). The aim is to choose the appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol (R) (1: 1)) and cosurfactant (Transcutol (R) HP) are formed by applying mixture design. 16 formulations were formulated, where the proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin (R) UFl2, Neusilin (R) FL2, Sylysia (R) 320 and diatomite were used as the carriers. The ratio of SNEDDS: carrier was 1: 1 or 2: 1. Dissolution testing was carried out in the rotation paddles apparatus. Characterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02 +/- 34.09 nm and PdI 0.184 +/- 0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia (R) 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate of carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability. PB - Savez hemijskih inženjera, Beograd T2 - Hemijska industrija T1 - Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist VL - 70 IS - 5 SP - 525 EP - 537 DO - 10.2298/HEMIND150623059K ER -
@article{ author = "Krstić, Marko and Ibrić, Svetlana", year = "2016", abstract = "One of the problems with orally used drugs is their poor solubility, which can be overcome by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). The aim is to choose the appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol (R) (1: 1)) and cosurfactant (Transcutol (R) HP) are formed by applying mixture design. 16 formulations were formulated, where the proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin (R) UFl2, Neusilin (R) FL2, Sylysia (R) 320 and diatomite were used as the carriers. The ratio of SNEDDS: carrier was 1: 1 or 2: 1. Dissolution testing was carried out in the rotation paddles apparatus. Characterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02 +/- 34.09 nm and PdI 0.184 +/- 0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia (R) 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate of carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability.", publisher = "Savez hemijskih inženjera, Beograd", journal = "Hemijska industrija", title = "Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist", volume = "70", number = "5", pages = "525-537", doi = "10.2298/HEMIND150623059K" }
Krstić, M.,& Ibrić, S.. (2016). Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist. in Hemijska industrija Savez hemijskih inženjera, Beograd., 70(5), 525-537. https://doi.org/10.2298/HEMIND150623059K
Krstić M, Ibrić S. Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist. in Hemijska industrija. 2016;70(5):525-537. doi:10.2298/HEMIND150623059K .
Krstić, Marko, Ibrić, Svetlana, "Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist" in Hemijska industrija, 70, no. 5 (2016):525-537, https://doi.org/10.2298/HEMIND150623059K . .