Particle agglomeration of chitosan–magnesium aluminum silicate nanocomposites for direct compression tablets

Exfoliated nanocomposites of chitosan-magnesium aluminum silicate (CS-MAS) particles are characterized by good compressibility but poor flowability. Thus, the aims of this study were to investigate agglomerates of CS-MAS nanocomposites prepared using the agglomerating agents water, ethanol, or polyvinylpyrrolidone (PVP) for flowability enhancement and to evaluate the agglomerates obtained as direct compression fillers for tablets. The results showed that the addition of agglomerating agents did not affect crystallinity, but slightly influenced thermal behavior of the CS-MAS nanocomposites. The agglomerates prepared using water were larger than those prepared using 95% ethanol because high swelling of the layer of chitosonium acetate occurred, allowing formation of solid bridges and capillary force between particles, leading to higher flowability and particle strength. Incorporation of PVP resulted in larger agglomerates with good flowability and high strength due to the binder hardening mechanism. The tablets prepared from agglomerates using water showed lower hardness, shorter disintegration times and faster drug release than those using 95% ethanol. In contrast, greater hardness and more prolonged drug release were obtained from the tablets prepared from agglomerates using PVP. Additionally, the agglomerates of CS-MAS nanocomposites showed good carrying capacity and provided desirable characteristics of direct compression tablets.     

Initial moisture content in raw material can profoundly influence high shear wet granulation process

The aim of this work is to demonstrate that uncontrolled initial moisture content in microcrystalline cellulose (MCC) can profoundly affect high shear wet granulation (HSWG) process. We show that granule tabletability is reduced by approximately 50% when initial moisture content in MCC increases from 0.9% to 10.5% while all other processing parameters remain unchanged. An important observation is that granule tableting performance deteriorates significantly when initial moisture content increases from 2.6% to 4.9%, which is considered normal variation in moisture content for typical MCC (3-5%). The deteriorated tabletability is largely caused by increased granule size. On the other hand, granule flowability improves continuously with increasing initial moisture content in MCC. The improved flowability is mainly a result of granule size enlargement. Clearly, moisture content of raw materials for a HSWG process must be carefully monitored and controlled to ensure a robust manufacturing process as required by the quality-by-design principle.     

Development of mini-tablets with 1mm and 2mm diameter

The feasibility of formulating mini-tablets with 1 mm diameter on a rotary-die press in comparison to mini-tablets of 2 mm was investigated. To gain insight into the production of 1 mm mini-tablets, three model drugs of different compression characteristics were chosen, namely quinine hydrochloride, ibuprofen and spray-dried gentian extract. A high drug load in combination with robust and reproducible mechanical properties was requested. Depending on the individual drug substance, mini-tablets were produced by direct compression or after roll-compaction/dry granulation. The tensile strength, mass, and their variation coefficients were determined to assess the mechanical properties of the tablets. The content uniformity and the dissolution behavior of selected batches were analyzed.For the first time 1 mm mini-tablets could be successfully produced by direct compression (90% quinine hydrochloride; 90% dried gentian extract) and after roll compaction (70% ibuprofen). Depending on the applied compression pressure, 1 mm mini-tablets with quinine hydrochloride exhibited robust mechanical properties (e.g. median tensile strength of 2.02 N/mm²) with equal or lower variance of distribution compared to the 2 mm compacts. With respect to content uniformity of dosage forms, 1 mm mini-tablets containing 80% quinine hydrochloride met the requirements of the European Pharmacopeia (AV = 6.8).     

Material properties on enamel and fissure of surface pre-reacted glass-ionomer filler-containing dental sealant

Purpose

In pediatric dentistry, sealants have been used to prevent caries. Due to its material properties such as fluoride-releasing ability and physical strength, surface pre-reacted glass (S-PRG) filler is added primarily to resin-based dental materials for clinical use. In this study, we investigated the properties of S-PRG filler containing sealant.

A statistical design to evaluate the influence of manufacturing factors on the material properties and functionalities of microcrystalline cellulose

The aim of this study is to statistically evaluate the effects of manufacturing factors on the material properties and functionalities of microcrystalline cellulose (MCC) products. How the material properties of MCC products dominate their functionalities was further explored. Results demonstrate that the desired material properties and functionalities of MCC products can be obtained by manipulation of the manufacturing factors using proper polynomial equations, and the key manufacturing factor is temperature. On the other hand, the functionalities can be quantitatively predicted by material properties. Meanwhile, the key material property is molecular mass in controlling MCC functionalities. The particle morphologies may also serve as important material properties. In conclusion, the careful control of temperature during the manufacture of MCC might minimize inter-batch variation. The correlation of the material properties of MCC products with their functionalities might help the formulation designer rationally select proper MCC products. The universal harmonization of MCC products might be achieved by the regulation of their molecular mass, surface roughness, and roundness.     

3种调拌方法对藻酸盐印模材料气泡及凝固状态的影响

目的: 比较全自动印模调拌机、顺时针手动和联合八字手动3种调拌方法对藻酸盐印模材料气泡含量、流动性等物理性能的影响。方法: 分别采用3种不同调拌方法调制藻酸盐印模材料,比较印模的气泡数量、总面积和流动性,调拌前、后温度变化以及工作时间和凝固时间差异。采用SPSS 24.0软件包对数据进行统计学分析。结果: 全自动调拌组气泡数量为（2.30±2.50）个,总面积为（0.17±0.18） mm²,小于顺时针手动调拌组数量[（59.60±14.19）个]和总面积[（7.41±2.24） mm²],差异有统计学意义（P<0.01）;顺时针手动调拌组流动性（39.52±0.85） mm,小于全自动调拌组[（50.78±0.90） mm]和联合八字手动调拌组[（50.36±1.75） mm],差异有统计学意义（P<0.01）;3种方法调印模的工作时间和凝固时间均符合临床要求。结论: 全自动调拌法印模在气泡含量、流动性等方面较佳。手动调拌中,联合八字调拌法有助于减少印模气泡与形变量,提高流动性。     

SonicFill声波流体树脂的研究进展

SonicFill声波流体树脂是近年来投入市场的一种大块树脂,其填料含量高,是唯一一种通过声波激活大块树脂黏度的复合树脂.声波通过手柄传达至树脂材料,使改良剂黏度下降,增加了复合材料的流动性.由于其固化深度达5 mm,节省椅位操作时间,广受临床医生欢迎.     

Use of a Fluidized Bed Hammer Mill for Size Reduction and Classification: Effects of Process Variables and Starting Materials on the Particle Size Distribution of Milled Lactose Batches

The process capability of a fluidized bed hammer mill was investigated with respect to four process variables, namely, rotational speeds of beater system and classifier wheel, airflow rates and length of grinding zones, as well as the particle size and flow property of the starting materials. The size distributions of all the milled lactose batches could be fitted to the Rosin Rammler distribution (RRD) function. The characteristic particle size (D_e) and uniform coefficient (n), which were derived from the RRD function, complemented the size at the 99th percentile of the cumulative undersize distribution (D₉₉) to characterize the lactose batches. Lower D_e and D₉₉ values indicate a finer powder while a higher n value indicates a narrower size distribution.

The beater speed played a critical role. Increasing the beater speed from 12000 to 21000 rpm generally resulted in an increase in n and a decrease in D₉₉ values due to the greater amount of milling energy supplied. The particle size and flow property of the starting material also played an important role at beater speed of 12000 rpm, where the lowest amount of milling energy was supplied. When a higher amount of milling energy was provided, the effect of particle size of the starting material was less significant. The other process variables exerted varying effects. Increasing the classifier wheel speed from 5000 to 15000 rpm decreased the D_e and D₉₉ and increased the n values of the milled lactose batches, provided sufficient milling energy was supplied to the lactose particles. Changing airflow rates from 80 to 90 m³/h generally resulted in larger D_e and D₉₉ values and lower n values as the higher airflow rate provided greater airflow‐induced kinetic energy that facilitated the passage of lactose through the classifier wheel. However, changing the long grinding zone to a short one did not significantly affect the D_e, D₉₉ and n values of the milled lactose batches produced. Small lactose particles of narrow size distribution could be obtained using the fluidized bed hammer mill upon gaining a better understanding of the milling process.     

Precipitated silica as flow regulator

Flow regulators are added to solid pharmaceutical formulations to improve the flow properties of the powder mixtures. The primary particles of the flow regulators exist in the form of huge agglomerates which are broken down into smaller aggregates during the blending process. These smaller aggregates adsorb at the surface of the solid's grains and thus diminish attractive Van-der-Waals-forces by increasing the roughness of the host's surface. In most cases amorphous silica is used as flow additive but material properties like particle size or bond strength influence the desagglomeration tendency of the agglomerates and thus the flow regulating potency of each silica. For some silica types we will show that the differences in their flow regulating potency are due to the rate and extent by which they are able to cover the surface of the host particles. Binary powder mixtures consisting of a pharmaceutical excipient and an added flow regulator were blended in a Turbula mixer for a defined period of time. As pharmaceutical excipient corn starch was used. The flow regulators were represented by a selection of amorphous silicon dioxide types like a commercial fumed silica and various types of SIPERNAT precipitated silica provided by Evonik-Degussa GmbH, Hanau, Germany. Flowability parameters of the mixtures were characterized by means of a tensile strength tester. The reduction of tensile strength with the blending time can be correlated with an increase in fragmentation of the flow regulator.