One of the problems with orally used drugs is their poor solubility, which
can be overcame by creating solid self-nanoemulsifying drug delivery systems
(SNEDDS). Aim is choosing 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? (1:1)) and cosurfactant (Transcutol? HP) are formed by applying
mixture design. 16 formulations were formulated, where 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? UFl2, Neusilin? FL2,
Sylysia? 320, diatomite were used as the carriers. The ratio of
SNEDDS:carrier varied (1:1, 2:1). Dissolution testing was carried out in the
rotation paddles apparatus. Caracterization 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? 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 carbamazepine, with conservation of the polymorphic form III CBZ and
potentially increased bioavailability.
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