85 % of active pharmaceutical ingredients (API) on the market are incorporated into the oral pharmaceutical dosage forms. A large proportion of APIs has poor water solubility, therefore improving the solubility of API is one of the key steps to achieve better bioavailability. The preparation of amorphous solid dispersions (ASD) by hot melt extrusion (HME) technology is one of the most used methods to improve the bioavailability of poorly soluble API. ASDs are dispersions of one or more APIs in a solid inert carrier, which reduces and inhibits crystal growth and nucleation during dissolution and therefore, maintains the concentration of the API above equilibrium.
As part of research work, we prepared 4 samples of ASD with HME at different process temperatures, screw rotation speeds and feeding rates of the blend. We used weakly basic API from class BCS II, and weakly acidic HPMCAS type L as carrier polymer. With further analyses, we investigated the influence of process parameters on ASD dissolution. We determined the glass transition temperature of the samples using differential dynamic calorimetry (DSC), and no differences were detected between the individual samples. The process of their dissolution in the biorelevant FaSSIF medium was monitored by scanning electron microscopy. At different time points, we observed the size, shape and number of particles on the surface of the ASDs after dissolution in the biorelevant FaSSIF medium at pH 6.5 and found that the particles grow with time to an equilibrium size of 140–200 nm, while their morphology does not change with time. The research has shown that different process parameters affect the size of the colloidal particles that are formed during dissolution. At the lowest tested pH value of 5.75 of the FaSSIF medium, no colloidal particles were developed within 5 minutes, at all other tested pH values (6.0, 6.25, 6.5) the particles were already developed. With the MicroFLUXTM device, we confirmed that smaller colloidal particles have a faster mass flow through the lipid membrane than larger particles. The Zetasizer Nano ZS device was used to determine the size and number of nanostructures formed during the dissolution of ASD in FaSSIF medium pH 6.5 at various time points, but no differences were observed between individual samples. Since the presence of micelles in the FaSSIF medium hindered the interpretation of the obtained results, we tried to remove them by centrifugation and filtration. The results of the ASD analyzes with HPMCAS type L were compared with ASD containing type M which were produced at comparable process parameters. In the case of type M, smaller colloidal particles were measured than in type L after 10 minutes of ASD soaking and a pH value of 6.5 of FaSSIF medium.
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