Many newly discovered pharmacologically active ingredients are poorly water-soluble. Consequently, the absorption and bioavailability of such drugs are compromised and higher dosages are required to achieve desired therapeutic concentrations. To reduce adverse effects related to higher administered dosages, it is possible to improve the drug solubility by incorporating the active pharmaceutical ingredients (APIs) into lipid formulations. Among the most studied are self-(micro)emulsifying drug delivery systems (S(M)EDDS), where API is already present in the dissolved state. S(M)EDDS spontaneously form oil-in-water (micro)emulsion in an aqueous medium of our gastrointestinal tract after oral intake. During the last ten years, research was widely focused on the S(M)EDDS solidification to optimize advantages of preferred solid pharmaceutical dosage forms while keeping their desired properties.
The aim of our work was the transformation of liquid S(M)EDDS into solid state by direct adsorption method and spray drying with the use of solid porous carriers, followed by evaluation of products. Carvedilol was used as a model of poorly soluble drug; it belongs to the Class II according to Biopharmaceutical Classification System because of its poor solubility and good permeability. In the process of making solid S(M)EDDS (S-S(M)EDDS), carvedilol loaded S(M)EDDS were adsorbed onto porous carriers (Aeroperl® 300 Pharma, Florite® R, Neusilin® US2, Syloid® 244 FP and Syloid® XDP 3050) in different ratios (1:1 and 2:1). Since incomplete desorption of API from carriers was reported in literature, the surface of used carriers was partially deactivated with partial pre-filling of pores with polymers (Pharmacoat® 606, PVP K30 and PVP K90) to achieve a higher API desorption from S-S(M)EDDS after redispersion.
S-S(M)EDDS were successfully produced with both solidification methods. Pre-filling of the pores lowered the capacity for adsorption of S(M)EDDS onto carrier but allowed a higher desorption of API in the medium with pH=1,2 and pH=6,8. The flowability of the products would have to be improved by addition of lubricants prior to compressing into tablets or filling into capsules. The wettability was determined by sessile drop method with water, S(M)EDDS and S(M)EDDS dissolution before and after the deactivation of carrier’s surface. Additionally, the wettability was measured on S-S(M)EDDS. The correlation between wettability of the carriers and S-S(M)EDDS characteristics was assessed by comparing deactivation of the surface, the rate of API desorption and yield of spray drying method. The wetting angle of water on S-S(M)EDDS was lower when the ratio between S(M)EDDS and carriers was higher, which suggests that more S(M)EDDS was adsorbed onto the surface. Partial deactivation of carrier’s surface resulted in a higher wetting angle, which shows that polymer was also adsorbed on the surface. API did not crystalize in S-S(M)EDDS according to our analysis with differential scanning calorimetry.
A desorption rate of API from S-S(M)EDDS observed by performing in vitro dissolution tests was fast, indicating the possibility of achieving a higher bioavailability using such systems. Because of a high dose of API released over a short period of time after oral intake, the drug metabolizing enzymes in the liver could be saturated, resulting in a lower first pass metabolism of carvedilol and subsequently, a higher bioavailability of the drug after oral intake.
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