Compression direct

Direct Compression. This process is relatively simple and time saving. AH the ingredients are blended and then compressed into the final tablet. This is an excellent method, but encumbered by a number of problems. Not all substances can be compressed directly, necessitating a granulation step. Likewise, the flow properties of many blends of fine, particle-sized powders are not such as to ensure even filling of the die cavities of tablet presses. In addition, air entrapment can occur. 

The availabihty of spray-dried lactose, microcrystaUine cellulose, and other excipients allows for the use of granular rather than powdered phases. This eliminates some of the problems of particle segregation according to size (demixing) and even flow to the die. Direct compression eventually may be the preferred method of tablet preparation. 

Turkoglu J, Ozarslan R, Sakr A. Artificial neural network analysis of a direct compression tabletting study. Eur J Pharm Biopharm 1995 41 315-22. 

Bourquin J, Schmidli H, van Hoogevest P, Leuenberger H. Pitfalls of artificial neural networks (ANN) modelling technique for data sets containing outlier measurements using a study of mixture properties of a direct compressed tablet dosage form. Eur J Pharm Sci 1998 7 17-28. 

Finally, the reason for not forcing dicalcium phosphate (a very valuable formulation aid in direct compression) beyond 50°C is that at higher temperatures (actually [57] above 70° C) it converts to the anhydrate, a conversion that is, curiously enough, catalyzed by water. In other words, the dihydrate will be autocatalytic in this respect at elevated temperatures, and it should not be ruled out based on high-temperature findings. 

Table 6 Comparative Properties of Some Directly Compressible Fillers ... 

Starch is often cited as a filler, but it is more commonly used in its dry state as a disintegrating agent. However, modified starches such as StaRx 1500 and National 1551 (partially hydrolyzed, or pregelatinized starch) are marketed for direct compression and appear to offer the advantage of substantial mechanical strength and rapid drug release. 

Soft gelatin capsules are not an inexpensive dosage form, particularly when compared to direct compression tablets [3]. There is a more intimate contact between the shell and its liquid contents than exists with dry-filled hard gelatin capsules, which increases the possibility of interactions. For instance, chloral hydrate formulated with an oily vehicle exerts a proteolytic effect on the gelatin shell however, the effect is greatly reduced when the oily vehicle is replaced with polyethylene glycol [3]. 

Bindschaedler and Gurny [12] published an adaptation of the simplex technique to a TI-59 calculator and applied it successfully to a direct compression tablet of acetaminophen (paracetamol). Janeczek [13] applied the approach to a liquid system (a pharmaceutical solution) and was able to optimize physical stability. In a later article, again related to analytical techniques, Deming points out that when complete knowledge of the response is not initially available, the simplex method is probably the most appropriate type [14]. Although not presented here, there are sets of rules for the selection of the sequential vertices in the procedure, and the reader planning to carry out this type of procedure should consult appropriate references. 

R Bodmeier, HG Chen. Evaluation of biodegradable poly(lactide) pellets prepared by direct compression. J Pharm Sci 78 819-822, 1989. 

Measurements of particle porosity are a valuable supplement to studies of specific surface area, and such data are particularly useful in the evaluation of materials used in direct compression processes. For example, both micromeritic properties were measured for several different types of cellulosic-type excipients [53]. Surface areas by the B.E.T. method were used to evaluate all types of pore structures, while the method of mercury intrusion porosimetry used could not detect pores smaller than 10 nm. The data permitted a ready differentiation between the intraparticle pore structure of microcrystalline and agglomerated cellulose powders. 

Brittle fracture indices were obtained for a series of compacted direct compression excipients that had been exposed to various degrees of ambient relative humidity [67], As illustrated in Fig. 9, compacts of the essentially... 

Flow behavior of powders is also of interest in direct compression. It is generally accepted that the flow rate initially increases with particle size, achieves a maximum in the range of 100-400 /um, and then decreases [85]. An excipient that has been well characterized is lactose, which undergoes particle fragmentation when compacted. For a-lactose monohydrate, it has been shown that the... 

On the loaded side of a slab subjected to an intense reflected blast wave, a region of the slab will fail if the intensity of the compressive wave transmitted into the slab exceeds the dynamic compressive strength of the material. For an intense wave striking a thin concrete slab, the failure region can extend through the slab, and a sizeable area turned to rubble which can fall or be ejected from the slab. For a thicker slab or localized loaded area, spherical divergence of the stress wave can cause it to decay in amplitude within the slab so that only part of the loaded face side is crushed by direct compression. 

The point to demonstrate is that resistance is lowest around the FRC. The curve rises at low lung volumes as there is direct compression of the vessels. At high lung volumes, the vessels are overstretched, which alters the flow dynamics and increases resistance further. The curve will be moved up or down by those other factors (above) which increase or decrease PVR. 

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