Preformulation studies testing systems

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]. 

Based on the major goal of preformulation—identification of possible failure in future development—numerous studies are performed to fully characterize prospective drug candidates. The major analytical technique in each preformulation group is liquid chromatography. Ninety percent of all analytical equipment in preformulation groups are HPLC systems equipped with UV and MS detection systems. HPLC is a fast and reliable method for concentration and identity determination by UV and/or MS detection, respectively. The type of HPLC methods differ based on the specific preformulation tests that will be described below. 

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