The main objective of this paper is to use Ordinal Logistic Regression Modeling (OLRM) to predict and to investigate the relationship(s) between the different types of failures encountered in tableting tools of pharmaceutical industry and relevant tablet- and punch attributes. This would help minimize the occurrence of such failures in and avoid potential failure occurrences in future punch designs. Three punch attributes (punch diameter, location and shape) and five product attributes (tablet mass (gm), hardness (Kp), thickness (mm), moisture content (percent loss on drying (LOD %)) and sieve size (mm)) have been investigated in terms of their relative contributions towards different failure types. The present OLRM model has been successfully applied to the predict failure types according to the aforementioned factors. Furthermore, OLRM quantitatively links and evaluates the effects and contribution of each of these factors to the occurrence of different failure types. The OLRM methodology has been validated conveniently and proved to be powerful prediction tool. This is indicated by the marginal 2.4% error percentage encountered.
In pharmaceutical industries, tablets are usually prepared by the instantaneous compression of powders between a two-punch set in a cylindrical die Fig. 1. The compression force may be supplied by either the lower or upper punch. Tablets are becoming complex and exotic in both shape and profile for brand identity marketing. As the tablets become more complex so does the tooling. Therefore, tooling strength and durability is a major consideration when designing a tablet.
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Fig. 1.
A schematic illustration of a tableting compression station [2].
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The complex design and function of tableting allows a limited number of tool materials; particularly steel, to be used for this purpose among the many steels available. Compaction of granules into a solid form (tablet), with sufficient hardness and bond strength, results in high forces on the tooling, not just static loading but cyclic loading inflicting both stresses and strains. Pharmaceutical tabletting tools facing various types of tool breakage/failure; these include punch-tip breakage/chipping, tip wear, punch distortion and shorter punch-lengths among others.
In this research, it is wanted to investigate the types of failures encountered in pharmaceutical tabletting punch sets and what root causes are involved in these failures using Failure Mode and Effects Analysis (FMEA). This is expected to help in choosing the right tool material, tablet profiles as well as appropriate operating and maintenance procedures to reduce and/or eliminate punch failures.
Pharmaceutical tablets are solid, flat or biconvex dishes prepared by compressing a drugs or a mixture of drugs, with or without diluents. They vary in shape and differ greatly in size and weight, depending on the amount of medicinal substances and the intended mode of administration. It is the most popular dosage form accounting for 70% of the total produced medicaments. All medicaments are available in the tablet form except where it is difficult to formulate [1]. A tablet should have; elegant product identity while free of defects like chips, cracks, discoloration, and contamination, sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing, chemical and physical stability to maintain its physical attributes over time, the ability to release medicinal agents in a predictable and reproducible manner, and finally should have a chemical stability over time so as not to allow alteration of the medicinal agents [1].
Typical production sequence of medical tablets, Fig. 2, includes a filling stage, a compression stage and ejection stage. In the filling stage the exact measurement is used to give accurate weight and dosage for the tablet while filling the bore of the die with granules.
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Fig. 2.
A schematic illustration of typical production sequence of medical tablets; filling, compression and then ejection stage [2].
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Compressing of granule is essential to provide the correct hardness and solidarity of the tablets. If a tablet is not compressed properly it can crumble. Normally a pre-compression is used prior to the main compression stage, the purpose of which is to remove excess air before the powder is fully compressed and the correct final pressure is reached. After compression an ejection mechanism lifts both lower and upper punches and ejects tablets into a collection tray and the entire cycle is repeated for each tablet.
In this research study Failure Mode and Effects Analysis (FMEA) has been applied to relate main types of failure that occur in pharmaceutical punch sets to their root causes both qualitatively and quantitatively (through OLR modeling). Types of failures experienced in tableting punches have been revealed to be affected by; punch diameter, punch location, punch shape, product mass, product hardness, product thickness, moisture content and product sieve size. Edge-breakage problems were found to account for 33% of failures; followed by length variation (23.9%) and then concentricity (23.4%). The most logical failure sequence which seems to fit the data presented in this study seems to start with length variation followed by concentricity and finally edge breakage/chipping. An OLR model has been obtained and was successfully applied for the prediction of potential failure type(s) based on punch and product attributes.
The OLRM is validated conveniently; it proved to be powerful prediction tool with minor percentage error value of 2.4%.
