Evaluation of tricalcium citrate as a direct compressible diluent using the SeDeM Expert Diagram System

Abstract

Oral administration of medicine is one of the most common delivery routes still in use today. Various dosage forms are administered via the oral route including tablets, capsules, syrups, solutions and emulsions. Tablets constitute a large part of orally available dosage forms due to ease of administration amongst other advantages. Tablets comprise a large part of the oral dosage form market due to a less complicated manufacturing method when compared to other dosage forms such as parenteral dosage forms. There are several tablet manufacturing methods of which direct compression is one of the most common methods. Direct compression also has an advantage over methods such as dry- and wet granulation for ingredients that are thermolabile and moisture sensitive can be included in the formulation. To manufacture tablets, excipients are usually included in tablet formulations. An important excipient is the filler, which constitutes the bulk of the volume of the tablet. Besides the excipients, it is essential that tablet formulations contain an active pharmaceutical ingredient (API), which provides the pharmacological effect associated with the specific medicine. Traditionally tricalcium citrate (TCC) was used as a calcium supplement and was recently investigated and used as a filler in tablet formulations, especially during direct compression. The SeDeM Expert Diagram System (SeDeM EDS) is a scientific approach that strives to characterise substances or mixtures based on their respective individual or collective suitability for direct compression. This characterisation is accomplished by evaluating twelve parameters based on powder flow and compression characteristics. Data obtained from a SeDeM EDS analysis, can be used during tablet pre-formulation to determine the theoretical amount of an excipient to add to the formulation to achieve optimal powder flow and compression properties. This excipient added to correct the powder properties is called the corrective excipient. Fillers also have a property called the dilution potential. Dilution potential refers to the extent of a diluent’s ability to contain an API, while still being able to produce quality tablets. This property is specific to a specific filler-API combination. The aim of this study was to characterise TCC according to the SeDeM EDS as well as compare TCC to other commonly used fillers, including Avicel® PH200, CombiLac®, Emcompress®, FlowLac®, MicroceLac®, and Tablettose® according to their SeDeM EDS profiles. A ranking order was established using these results. The theoretical dilution potential for the abovementioned fillers was also determined for different APIs (furosemide, paracetamol and pyridoxine) using the SeDeM EDS. Afterwards, the true or real dilution

potential was also determined experimentally and compared to the theoretical dilution potential. The results obtained indicated that TCC is suitable to be used during tablet manufacturing using the direct compression manufacturing method. While other fillers other also obtained SeDeM EDS values indicating suitability for direct compression, TCC and MicroceLac® were the only fillers to pass all the SeDeM EDS requirements to be a filler suitable for direct compression. TCC was also able to form acceptable tablets containing furosemide, paracetamol, and pyridoxine as APIs.