Compaction simulator formulations

When the work is carried out on a compaction simulator, it is possible to subject the formulation to high-speed tableting cycles in order to evaluate strain forces in the compacts. This work can be of utmost importance, since it appears that strain rates can exert strong influences on a variety of tablet properties [64]. The information gathered in this way can be used to aid in the transfer of the manufacturing process among different types of instrumentation, and to aid ir the technology transfer process. 

The use of compaction simulators was first reported in 1976. Since then, a variety of simulators have been developed. Hydraulic simulators, as well as mechanical simulators, are available to characterize raw materials, drug substances, and formulations, as well as to predict material behavior on scale-up. The appeal of simulators is due to the fact that they purport to provide the same compaction profile as experienced on a tablet press while using only gram or even milligram quantities of powders. Compaction simulators can achieve high speeds, as would be experienced on a production tablet press, and can be instrumented to measure a variety of parameters, including upper and lower punch force, upper and lower punch displacement, ejection force, radial die wall force, take-off force, etc. Summaries on the uses of simulators and tablet press instrumentation can be found in (19,20). 

Some of these measurements can also be performed on compaction simulators, which are single-stroke presses specifically designed to evaluate individual materials and/or full formulations [ 12]. The simulation of short dwell times and of many different profiles for punch movement in real time are the advantages of this type of measurement. Recent work with a compaction simulator has even included a thermodynamic analysis of compaction [13,14]. 

A small rotary press is most likely used when the initial formulation and process is developed at small scale. However, a large rotary press, used in a production area, may have significant differences in the number of stations, dwell time, and compression speed compared with smaller compression machines. Thus, early formulation design should consider the performance requirements of commercial production. Compaction simulators provide a useful tool able to reproduce the punch speeds of production machines and require only small quantities of powder blends for testing.86 The simulators can play an important role in formulation and process development and can also facilitate the technical transfer from development to commercialization. 

Using mechanical compaction simulators allows us to simulate the tableting process of rotary tableting machines to a greater extent than when using hydraulical compaction simulators. Thus they will be mainly used in formulation development and scale-up. 

However, for mechanical compaction simulators the movement of the punches is mechanically determined and, compared to hydraulic compaction simulators, not freely programmable. Thus, for basic material characterization and early formulation development, hydraulical compaction simulators can be advantageous. 

The compaction properties of pharmaceutical formulations can be studied experimentally using a variety of techniques, ranging from instrumented production presses to compaction simulators, and methods of analysis. The results are usually plotted as porosity-axial stress functions, which is of interest to compare different materials. However, there are some drawbacks on this type of evaluation. As mentioned by Cunningham et al. [20], this approach is deficient once it considers only the average stress along the direction of compaction, ignoring radial stress transmission and friction. 

As a high-speed single station press, mechanical compaction simulator will be able to plot compressibility profiles, Heckel graphs, calculate work of compaction, and virtually any other imaginable variable that is of interest to formulators. Tensile strength of tablets made on a Betapress and The Presster was similar. ... 

Asgharnejad, M. Storey, D. Application of a compaction simulator to the design of a high-dose tablet formulation. Part I. Drug Dev. Ind. Pharm. 1996, 22 (9 10), 967-975. 

Lubrication of the die and punches is essential for many solid dosage formulations to prevent material sticking to the equipment surfaces during tablet production. The amount of lubrication, technique to apply the lubrication, and method of addition can have large effects on the die wall friction during the compaction process. Various techniques exist for lubrication of the compaction simulator dies. The most prominent method for manual die lubrication is to brush the die with a magnesium stearate suspension (e.g., in methanol). This technique is easily controlled however, it can be time intensive and may not be... 

Compaction simulators are beneficial solid dosage formulation development because of their manufacturing versatility. They can be outfitted with a variety of tooling designs and can simulate a nearly infinite range of realistic compre.ssion profiles through the... 

As reported earlier, compaction simulators can be equipped to replicate the compression process of a roller compactor. Zinchuk et al. describe how a compaction simulator can be used to produce ribbons and determine the formulation specific compactability relationship (tensile strength vs. solid fraction) (Fig. 27) (4), Since compacts produced under equivalent stress-strain conditions exhibit similar mechanical properties, the ribbon solid fraction and/or tensile strength can be used as a scale-up factor for pilot and eventually commercial scale manufacturing. 

FIGURE 30 Compaction profiles for tablets of different formulations evaluated using a compaction simulator Source Adapted from Ref. S3. 

The differences in punch speed at initial contact and dwell times, the period at which the compact is held at maximum compression, are likely to affect the nature of any tablets which have any viscoelastic components. Compaction simulators that are able to reproduce the punch speeds of production machines, yet only require small quantities of powder for testing, can have a valuable role to play in formulation development. 

One of the disadvantages of this roller press simulator was that it still needed a relatively large amount of material and movement was slow and limited. There is a special need in the pharmaceutical industry to accurately predict the compaction behavior of dry powder formulations in roller presses during the development of... 

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