Polymer Characteristics for Drug Layering on Particles Using a Novel Melt Granulation Technology, MALCORE®.

MALCORE®, a novel manufacturing technology for drug-containing particles (DCPs), relies on the melt granulation method to produce spherical particles with high drug content. The crucial aspect of particle preparation through MALCORE® involves utilizing polymers that dissolve in the melt component, thereby enhancing viscosity upon heating. However, only aminoalkyl methacrylate copolymer E (AMCE) has been previously utilized. Therefore, this study aims to discover other polymers and comprehend the essential properties these polymers need to possess. The results showed that polyvinylpyrrolidone (PVP) was soluble in the stearic acid (SA) melt component. FTIR examination revealed no interaction between SA and polymer. The phase diagram was used to analyze the state of the SA and polymer mixture during heating. It revealed the mixing ratio and temperature range where the mixture remained in a liquid state. The viscosity of the mixture depended on the quantity and molecular weight of the polymer dissolved in SA. Furthermore, the DCPs prepared using PVP via MALCORE® exhibited similar pharmaceutical properties to those prepared with AMCE. In conclusion, understanding the properties required for polymers in the melt granulation process of MALCORE® allows for the optimization of manufacturing conditions, such as temperature and mixing ratios, for efficient and consistent drug layering.

Impact of Properties of Hydrated Silicon Dioxide as Core Material on the Characteristics of Drug-containing Particles Prepared by the 2-step Process Melt Granulation Technology, MALCORE®.

Drug-containing particles (DCPs) are frequently used as cores in the development of solid oral dosage forms. The wet layering technique, which is a typical approach for preparing DCPs, requires the use of solvents and a long manufacturing time. In our previous study, we developed a novel manufacturing technology, MALCORE®, which can solve these problems through melt granulation. However, particle size control methods for DCPs in MALCORE® and the effect of the physical properties of the hydrated silicon dioxide (HSD) used for the core have not been clarified. The aim of this study was to examine the effects of the particle and pore sizes of HSD on the properties of the prepared DCPs. The results showed that the DCPs prepared using MALCORE® could be controlled by the particle size of HSD. The drug-loading efficiency tended to decrease as HSD particle size increased. Additionally, the amount of drug layering in DCPs increased as the pore size of HSD increased, but HSDs with a pore size much larger than the particle size were not able to properly layer the drug. These findings are helpful for applying MALCORE® to a variety of oral drug formulations.

Solid-state NMR characterization of triacylglycerol and polysaccharides in coffee beans.

It is important to understand the structural characteristics of triacylglycerol (TAG), polysaccharides and trace elements in coffee beans, so that residues can be reutilized in applications including biodiesel oils. Here, we performed 1H and 13C solid-state NMR measurements on Indonesian green beans, roasted beans, and spent coffee grounds (SCGs). In the NMR spectra, there were liquid-like TAG containing linoleic acids based on observed signals of -CH=CH-CH2-CH=CH- group in an acyl chain, which play a role in decreasing TAG's melting point. We found TAG was still abundant in the SCGs from NMR spectra. After lipids were removed from SCGs, the intensity of the TAG signal decreased considerably, with approximately 64% of the TAG was successfully extracted. We described the chemical structure of TAG in coffee beans and demonstrated that it is possible quantify the amount of extracted TAG using solid-state NMR.

Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 µm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 µm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm2, and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs.