Yes / Twin screw granulation (TSG) has been applied to wet granulation, although its application in melt granulation has been more limited. This work explores potential advantages of hot melt granulation using twin screw extrusion. Four main operating and formulation parameters were investigated: screw speed, number of mixing elements, temperature, and binder percentage. Combinations of these factors were then studied to determine their impact on the quantity and characteristics of granules within the desired size range of 125 - 1000 µm. A screening design of experiments (DOE) study was used with each factor set at three levels, to investigate individual factor effects and interactions. Two types of mixing elements were studied: kneading block (KB) and chaotic elements. The type and number of mixing elements were found to be paramount in contributing to the quantity and characteristics of granules formed. Results obtained agreed with previous findings in literature on the influence of different screw elements on the characteristics of granules formed by twin screw granulation. Additionally, the study revealed the unique impact which different mixer elements have on both granule production and characteristics. Depending on the specific need or use of granules in required applications, the granulation process can be effectively designed to meet the end product quality and outcome.

Continuous wet granulation using a twin-screw extruder has attracted considerable attentions in pharmaceutical industry as it ensures consistent tablet quality at a high production rate. However, challenge still exists in controlling desired granule properties especially when different sized twin-screw granulators are used. This study therefore explored the potential of scalability of two sized twin-screw extruders and the how raw materials affect granules properties in two twin-screw extruders. The first study focuses on aspects of scaling using two twin-screw extruders, 18mm and 27mm. Dimensionless groups including Fr Number, Powder Feed Number and Degree of Fill (<30%) were studied to observe their influences on granule attributes. It was found that these dimensionless groups demonstrated inconsistent effects on granule properties and the effect of Powder Feed Number was highly dependent on Degree of Fill. Different extruder still exerts significant impact on granule properties. A scaling rule was established for median granule size (d50) only, but only moderate degree of fit was found. Although a considerable number of studies have been published on controlled-release and extended-release excipients, little attentions have been given to the influence of microcrystalline cellulose (MCC) grades in twin-screw wet granulation. The second study therefore investigated the processability of five grades MCC from the Avicel® PH family using two twin-screw extruders again, 18mm and 27mm. Granule attributes including particle size, density, moisture, and strength were tested and it was found that MCC inherent density has the most significant impact on granule properties while particle size of MCC has minor positive effect on granule size. This study also concluded that better granule flowability and uniformity can be achieved by using low moisture, larger particle size and high density MCC as excipients. / Thesis / Master of Applied Science (MASc)

Twin screw wet granulation has been proved as a feasible alternative for traditional batch granulation process due to its continuous processing feature; considered as a significant processing method especially in the pharmaceutical industry. This thesis will explore the processibility of twin screw wet granulation with various formulations. The first section of the thesis focused on examining the processibility of wet granulation in a twin screw while using various grades of hydroxypropyl methylcellulose (HPMC) as an extended-release excipient. The method to find the processibility was by modifying the liquid-to-solid ratio for each formulation. The process window was defined by examining the amount of granules that fall in a pre-determined acceptable size range. This part focused on three substitution types of HPMC (Type 2910, Type 2208, and Type 2906) that varied in molecular weights. It was found that only Type 2910 HPMC showed a shift in the process window (also known as granulation range) in relation to the molecular weight of the formulations. A higher demand for binder liquid was found for higher molecular weight Type 2910 HPMC in order to form granules with acceptable sizes. The second part of this thesis was focused on understanding the process variables that might influence the processibility of the HPMC formulations. This part examined the impact of feed rate on the granulation range of Type 2910 HPMC specifically was examined. Multiple feed rates were tested, and it was found that the granulation range for lower molecular weight Type 2910 HPMC was easier to shrink when higher feed rates were applied. A transition in the granule formation method from liquid-bridging to compaction with respect to the feed rate was found for low molecular weight HPMC, whereas the high molecular weight HPMC always formed granules through compaction at all feed rates due to strong water retainability. / Thesis / Master of Applied Science (MASc)