Compressibility behavior of pioglitazone hydrochloride in mannitol-based formulations: An investigation using compaction simulator and QbD approach.

This study aimed to investigate the compressibility properties of Pioglitazone Hydrochloride (PGZ) oral dispersible tablets using a compaction simulator. The tablets were prepared and formulated by direct compression method with varying particle sizes of PGZ in mannitol-based formulations, containing Ludiflash® and its corresponding physical mixture. All formulations were compressed at different compaction forces (5kN-20kN). Powders were evaluated for their tablet properties, such as hardness, friability, disintegration time and dissolution rate. Results showed that all formulations exhibited good compressibility properties. The compaction force and choice of excipient played a vital role in formulation performance and drug release profile. With the use of Minitab 19™ an optimized formulation was derived and all predicted outputs was seen to be within range after evaluations. In conclusion, the combined use of the compaction simulator and Minitab 19™ were found to be useful tools in predicting the compressibility properties of PGZ and therefore developing a robust oral dispersible tablet. These findings suggest that the compressibility properties of PGZ oral dispersible tablets can be effectively modified by adjusting the critical process parameters (CPP). Hence, providing valuable insights into the compressibility behavior of PGZ oral dispersible tablets and also aiding in the development of optimized tablet formulations.

Critical Tools in Tableting Research: Using Compaction Simulator and Quality by Design (QbD) to Evaluate Lubricants' Effect in Direct Compressible Formulation.

As commonly known, the product development stage is quite complex, requires intensive knowledge, and is time-consuming. The selection of the excipients with the proper functionality and their corresponding levels is critical to drug product performance. The objective of this study was to apply quality by design (QbD) principles for formulation development and to define the desired product quality profile (QTPP) and critical quality attributes (CQA) of a product. QbD is a risk- and science-based holistic approach for upgraded pharmaceutical development. In this study, Ibuprofen DC 85W was used as a model drug, Cellactose® 80 along with MicroceLac® 100 as a filler, and magnesium stearate, stearic acid, and sodium stearyl fumarate as lubricants. By applying different formulation parameters to the filler and lubricants, the QbD approach furthers the understanding of the effect of critical formulation and process parameters on CQAs and the contribution to the overall quality of the drug product. An experimental design study was conducted to determine the changes of the obtained outputs of the formulations, which were evaluated using the Modde Pro 12.1 statistical computer program that enables optimization by modeling complex relationships. The results of the optimum formulation revealed that MicroceLac® 100 was the superior filler, while magnesium stearate at 1% was the optimum lubricant. A design space that indicates the safety operation limits for the process and formulation variables was also created. This study enriches the understanding of the effect of excipients in formulation and assists in enhancing formulation design using experimental design and mathematical modeling methods in the frame of the QbD approach.

Evaluation of Lactose-Based Direct Tableting Agents' Compressibility Behavior Using a Compaction Simulator.

OBJECTIVES: A compaction simulator (CS) is a single-punch instrument that records data during the powder compaction process. The aim of the study was to determine the behavior of lactose-based direct tableting agents (DTAs) by CS. The data recorded were used to evaluate the flowability and compressibility of powders. The focus of the study was on comparing the compressibility of StarLac® [alpha lactose monohydrate (85%) and white maize starch (15%)] and FlowLac®100 (spray-dried alpha lactose monohydrate) in order to make tablets containing poorly flowable paracetamol. MATERIALS AND METHODS: Two lactose-based DTAs were used. Physical characterization of these powders was done by measuring bulk, tapped, and true densities alongside scanning electron microscopy analysis. Flow properties were then calculated by the angle of repose, Hausner ratio, and Carr's compressibility index. Force, in-die thickness, and punch displacement data produced by the CS were captured during in-die compression. Compressibility was calculated using the Heckel equation. RESULTS: The physical characterization test results showed no significant difference between the two DTAs. Hardness results revealed that tablet formulations containing FlowLac® had higher sensitivity to an increase in compression force in comparison with StarLac®. From the Heckel plots generated by the CS during the compression cycle, yield pressure (Py) values were calculated for FlowLac®100 and StarLac®. The Heckel parameter (Py) for FlowLac®100 and StarLac® was calculated as 87.5 MPa and 85.2 MPa, respectively, during the compaction cycle at 5 kN. These data indicated that both powders are compressible and have brittle behavior. CONCLUSION: StarLac® is less brittle, which was shown by its lower sensitivity to compression force. Py values obtained from the Heckel equation described the plasticity of particles, which gives distinct information on the compressibility of both DTAs in real time during the compaction cycle.

Investigation of the Compressibility Characteristics of Paracetamol using "Compaction Simulator".

OBJECTIVES: This study was performed to understand the behavior of poorly compressible paracetamol powder using a compaction simulator (CS), equipment that records data during the compaction process. The aim was to investigate the compressibility of paracetamol tablets using a dry granulation (slugging) process, with different formulation compositions. MATERIALS AND METHODS: Formulations were prepared to observe the effect on compressibility with two different lactose-based fillers, Flowlac®100 and Granulac®70, and a binder, Kollidon® K90. In each combination, a total of four formulations were prepared with paracetamol to filler ratios of 1:1 and 0.8:1. Tablets were produced by single punch (11.28 mm) CS at six different pressures (152, 210, 263, 316, 400, and 452 MPa). During compression, upper punch displacement and force data were produced by the CS equipment. The compressed tablets were tested for hardness, thickness, and weight variation and compared with each other. RESULTS: All formulations reached maximum tensile strength at compaction pressures between 263 and 316 MPa. In the formulations without binder, those containing Granulac®70 had higher tensile strength than those containing Flowlac®100 at both filler ratios. The results obtained indicated that the addition of binder to the formulations (F-45-1, F-45-2, F-50-3, and F-50-4) improved the compressibility of paracetamol. Formulation F-45-2, containing Flowlac®100 and binder, showed better compressibility at 2.9 MPa tensile strength. Data from the CS were used to compare Young's modulus and work of compaction on selected formulations (F-45-1 and F-45-2). CONCLUSION: The proposed lactose-based filler, Flowlac®100, with low pressure can be successfully applied for improving the compressibility of paracetamol. An optimum formulation can be designed with smaller amounts of materials using a compaction simulator.