The processing of liquisolid systems (LSS), which are considered a promising approach to improving the oral bioavailability of poorly soluble drugs, has proven challenging due to the relatively high amount of liquid phase incorporated within them. The objective of this study was to apply machine-learning tools to better understand the effects of formulation factors and/or tableting process parameters on the flowability and compaction properties of LSS with silica-based mesoporous excipients as carriers. In addition, the results of the flowability testing and dynamic compaction analysis of liquisolid admixtures were used to build data sets and develop predictive multivariate models. In the regression analysis, six different algorithms were used to model the relationship between tensile strength (TS), the target variable, and eight other input variables. The AdaBoost algorithm provided the best-fit model for predicting TS (coefficient of determination = 0.94), with ejection stress (ES), compaction pressure, and carrier type being the parameters that influenced its performance the most. The same algorithm was best for classification (precision = 0.90), depending on the type of carrier used, with detachment stress, ES, and TS as variables affecting the performance of the model. Furthermore, the formulations with Neusilin^® US2 were able to maintain good flowability and satisfactory values of TS despite having a higher liquid load compared to the other two carriers.

Background/Objectives: Improving the production rates of modern tablet presses places ever greater demands on the performance of excipients. Although co-processing has emerged as a promising solution, there is still a lack of directly compressible excipients for modified-release formulations. The aim of the present study was to address this issue by investigating the potential of novel co-processed excipients for the manufacture of modified-release tablets containing ibuprofen. Methods: The excipients were prepared by melt granulation of lactose monohydrate with glyceryl palmitostearate as a binder. The influence of glyceryl palmitostearate particle size, ibuprofen content, compression pressure, and compression speed on the compaction behavior of the tablet blends was analyzed. Results: Novel co-processed excipients ensured good flowability and acceptable mechanical properties of the tablets containing up to 70% ibuprofen. Furthermore, lipid-based co-processed excipients proved to be very promising for directly compressible formulations with high-dose, highly adhesive active pharmaceutical ingredients such as ibuprofen, as they do not require additional lubricants. The influence of compression speed on the tensile strength of the tablets prepared was not pronounced, indicating the robustness of these directly compressible excipients. The investigated lipid-based excipients enabled a prolonged release of ibuprofen over 10 h. Conclusions: The novel lipid-based co-processed excipients have shown great potential for directly compressible formulations with modified release of high-dose, challenging active pharmaceutical ingredients.

Green fluidized bed granulation is a new, environmentally friendly alternative to wet granulation, as drying is not required due to the use of a small amount of water (up to 5%). The goal of this study was to investigate the influence of water content and process parameters on the properties of granulates and compacts obtained by this method. Granulates and compacts were prepared according to a 24 full factorial design, with the following factors investigated: water content and feed rate, spray air pressure, and compression load. The response variables were: network of compression, detachment and ejection stresses, tensile strength, elastic recovery, and disintegration time of the compacts. Granulates were characterized by particle size distribution and flowability. Higher water content (5%) led to the formation of somewhat larger granules with better flow properties. All compacts showed good mechanical properties, with tensile strength greater than 1.5 MPa, regardless of the compression pressure applied. Compression load and water feed rate significantly influenced tensile strength, with higher compression load and slower water feed rate resulting in stronger interparticulate bonding. The investigated factors and their interactions significantly affected detachment and ejection stresses. However, despite the influence of these factors, all compacts exhibited rather low values for these parameters (< 0.7 MPa). Compression load and water content significantly influenced net work of compression, elastic recovery, and disintegration time. The results obtained indicate the significant potential of this novel, environmentally friendly granulation method for producing tablets with good mechanical properties and rapid disintegration.

Liquisolid systems (LSS) are an effective approach to improve bioavailability of poorly soluble drugs. A key step in their formulation is selecting a carrier with suitable absorption capacity, which, together with coating agent, converts the drug dispersion into dry powder with good flowability and tabletability [1]. The aim of this research was to improve the dissolution rate of atorvastatin calcium (ATC) from tablets by formulating LSS with carrier Syloid® XDP3150. LSS was prepared by mixing the liquid phase (a 2% solution of ATC in polyethylene glycol 400) with carrier, coating agent/colloidal silicon dioxide, superdisintegrant/croscarmellose sodium, and lubricant/sodium stearyl fumarate, using a pestle and mortar. Flowability of the prepared mixture was tested, and after compression using a laboratory compaction simulator (500 kg, 60 mm/min), the tablets' mechanical properties, disintegration time, and ATC dissolution rate were determined. Prepared mixture showed good flowability (Carr index=13%). Tensile strength was 1.02 MPa, while detachment and ejection stresses were 4.32 MPa and 3.05 MPa, respectively. Elastic recovery was 31.6%. Good flowability and acceptable compaction properties (tensile strength >1MPa; ejection stress <5MPa) [2,3] were achieved despite the high proportion of liquid phase present (35%). Disintegration time was short (90% after 10 min) than from tablets of the same composition without polyethylene glycol 400 (~50% after 60 min). The results demonstrate the significant potential of LSS with a mesoporous silica-type carrier as a method to achieve improved dissolution of ATC from tablets.