Compressibility preformulation studies

During the preformulation stage, the chemical and physical properties of the dmg moiety are studied exhaustively to ensure stabdity, safety, bioavadabdity, and therapeutic efficacy. Tablets are produced directly by compression of powder blends or granulations, which include a small percentage of fine, particle-sized powders. 

One approach to the study of solubility is to evaluate the time dependence of the solubilization process, such as is conducted in the dissolution testing of dosage forms [70], In this work, the amount of drug substance that becomes dissolved per unit time under standard conditions is followed. Within the accepted model for pharmaceutical dissolution, the rate-limiting step is the transport of solute away from the interfacial layer at the dissolving solid into the bulk solution. To measure the intrinsic dissolution rate of a drug, the compound is normally compressed into a special die to a condition of zero porosity. The system is immersed into the solvent reservoir, and the concentration monitored as a function of time. Use of this procedure yields a dissolution rate parameter that is intrinsic to the compound under study and that is considered an important parameter in the preformulation process. A critical evaluation of the intrinsic dissolution methodology and interpretation is available [71]. 

Solid-state characterization is one of the most important functions of the preformulation group, which is assigned the responsibility of making recommendations for further formulation work on a lead compound. Physical properties have a direct bearing on both physical and chemical stabilities of the lead compound. Much of the later work on formulation will depend on how well the solid state is characterized from the decisions to compress the drug into tablets to the selection of appropriate salt forms. The studies reported in this section, of course, apply to those drugs that are available in solid form, crystalline or amorphous, pure or amalgamated. 

A number of other studies can be performed on a candidate drug to determine other important solid-state properties, for example, particle size, powder flow and compression and polymorphism. Therefore, when a sample undergoes initial preformulation testing the following parameters should be noted particle size, true, bulk and tapped density, surface area, compression properties and, powder flow properties. Some of these factors will be discussed in this chapter others, however, are dealt with in more detail in Chapter 11 on Solid Oral Dosage Forms. 

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