Flowability particle size limitations

When the various solid forms exhibited by a drug substance have been found and characterized, important properties of each form should be determined and compared. Some properties, such as melting point and hygroscopicity, will have been obtained in the form characterization process. Investigations of other properties will require directed research efforts. We will limit our discussion to selected properties that reflect internal arrangement (thermodynamic stability, solubility, and dissolution rate), and will not cover bulk properties which may be greatly affected by both solid form and particle morphology (flowability, particle size, etc.). 

In the manufacture of tablets it is important to define and appreciate the physical properties of the active substance, in particular particle size and flowability. The technology involved in direct compression assumes great importance in tablet formulations because it is often the least expensive, particularly in the production of generics that the active substance permits. The limiting factors are the physical properties of the active substance and its concentration in the tablets. Even substances such as ascorbic acid, which are not generally suitable for direct compression owing to the friability of the crystals, can normally be directly pressed into tablets at concentrations of 30-40%. Ffowever, this technique is not as suitable if the content of ascorbic acid is higher. This limit may be shifted upward by special direct-compression auxiliaries, for example, Ludipress (BASF). 

Since the choice of the atomizer is very crncial, it is important to note the key advantages and limitations of different atomizers (centrifngal, pressnre, and pneumatic atomizers). Other atomizers, e.g., ultrasonic atomizer, can also be nsed in spray dryers (Bittern and Kissel 1999) but they are expensive and have rather low capacity. Although different atomizers can be used to dry the same feedstock, the final product properties (bulk density, particle size, flowability, etc.) are quite different and hence a proper selection is necessary. 

Excipients could usefully be classified or tested according to their properties at three levels, viz. molecular, particulate, and bulk properties. Those are tested for by the manufacturer of a dosage form. It is not clear which of those properties should be covered by the official compendia. Testing of functionality, i.e., at particulate or bulk level, does not seem to be possible yet. Typical tests are bulk density, specific surface area, flowability, and particle size distribution. However, the standardization of methodology in compendia, without specification limits, will probably be of help for both vendor and buyer. Therefore, functionality related tests are now being proposed in the pharmacopoeias. As excipients are getting more complex, their analytical characterization is very important. Interesting opportunities lie ahead, particularly with macromolecular separation, MALDI-TOF-MS, and spectrometric methods such as NIR. 

Viscosity, flowability limit Size (if powder particles)... 

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