Enhancement of dissolution rate and subsequently bioavailability of a poorly water–soluble drug is a very challenging task in drug development. Nearly 40 % of the approved chemical entities on the market have poor water solubility. They include naproxen, a non–steroidal analgesic. To improve the dissolution rate of this active substance three–component solid dispersions of naproxen with a surfactant and mesoporous silicon dioxide were prepared as part of the master's thesis using a method of melting under an infrared heater. The prepared solid dispersions were evaluated for amorphousness, component interactions, release, and physical stability.
Firstly, excipients for incorporation into solid dispersions were selected. Two types of mesoporous silica, Syloid® XDP 3050 and XDP 3150, were chosen as the appropriate carriers due to their good flow properties, which are important for the formation of the final pharmaceutical form, such as tablets or capsules. Cremophor® A25, ceteareth–25, was chosen as a surfactant, as it effectively reduces the melting point of naproxen, provides optimal conditions for the preparation of solid dispersions, and has a high dissolution rate in water. Subsequently, solid dispersions with different proportions of naproxen (20, 30, and 40 %) and surfactant (5, 10, 20, and 30 %) in a mesoporous carrier were prepared.
In vitro release tests were performed with a USP type II device (paddle) in an acidic medium. By preparing solid dispersions, the dissolution rate of naproxen was successfully increased compared to the physical mixture and the pure active ingredient (p < 0.05). The percentage of naproxen released from solid dispersions averaged 22 % in the first 5 minutes, while only 1 % of pure naproxen dissolved during the same time. The differences between the release profiles were most likely due to the transformation of the crystalline form of the active ingredient into an amorphous one, as indicated by the absence of melting peaks on the thermogram and reduced intensity of naproxen peaks on the solid dispersion diffractogram. Differences between releases of naproxen from the two mesoporous carriers, which differed in particle size and specific surface area were detected. With solid dispersion containing XDP 3050 carrier, the faster release was achieved than with XDP 3150, which may be due to the larger dissolution surface, and the shorter path of the active ingredient molecule to reach the medium.
The lower content of naproxen (20 %) in the solid dispersions enabled faster release than the higher one (30 %) since in the latter the proportion of naproxen was present in crystalline form on the surface of the carrier particles. As the naproxen content increased, the specific surface area of the particles decreased due to the filling of the pores, which was confirmed by nitrogen adsorption measurements. The final mean percentage of naproxen released from solid dispersions was 36 %, which is not much higher than dissolved pure naproxen (29 %). However, the burst release effect of naproxen from solid dispersions is associated with the rapid onset of action of the drug.
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