Solid dispersions are dispersions of active pharmaceutical ingredients in a solid, inert carrier, typically produced through methods such as hot-melt extrusion and spray drying. The advantages of solid dispersions include an increased dissolution rate of poorly water-soluble drugs (BCS class II, IV), which enhances their bioavailability. Due to poor flow properties of the mixtures and reduced compressibility, the tableting process can be challenging, but the addition of excipients improves the properties of the mixture for tableting.
The aim of this thesis was to determine how different types of fillers, superdisintegrants, and the proportion of placebo extrudate affect the flowability and compressibility of the mixtures for tableting, as well as the hardness and disintegration time of the resulting tablets.
We examined the impact of the fillers such as microcrystalline cellulose (MCC), dicalcium phosphate, and lactose, as well superdisintegrants such as Na-carmellose (Na-CMC), crospovidone, and sodium starch glycolate on the properties of tablets composed of a placebo copovidone extrudate. We examined the influence of several input variables, including the proportion of placebo extrudate, the type of filler, and the type of superdisintegrant, using the Design of Experiments (DoE) approach.
The results showed that flowability, compressibility, tabletability, and disintegration of the tablets were significantly influenced by the proportion of placebo extrudate, the type of filler, and the type of superdisintegrant. The best flow properties were observed in mixtures with a 25% proportion of placebo extrudate, dicalcium phosphate as the filler, and Na-CMC as the superdisintegrant. Mixtures with 25% placebo extrudate and MCC as the filler exhibited the best compressibility and tabletability, both of which significantly decreased with an increased proportion of placebo extrudate. The mixture with MCC also showed a higher elastic relaxation index compared to the mixture with dicalcium phosphate. In terms of disintegration time, the shortest times were observed in mixtures with a 25% placebo extrudate content and MCC or dicalcium phosphate as the filler. With an increased proportion of placebo extrudate, tablet disintegration time was significantly prolonged.
Based on the results, we were able to evaluate the most appropriate tablet composition for the desired properties. For prototype development, the most suitable composition would be a mixture with 25% placebo extrudate, MCC or dicalcium phosphate as the filler, and Na-CMC as the superdisintegrant.
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