Dosage forms physical properties

Lee, J. Drug nano- and microparticles processed into solid dosage forms physical properties. J. Pharm. Sci. 2003, 92 (10), 2057-2068. 

The physical characteristics should be considered (in combination as appropriate) in relation to the proposed dosage form and route of administration. Factors to be considered extend to solubility characteristics, crystal form and properties, moisture or solvent content, particle size and size distribution (which may affect bioavailability, content uniformity, suspension properties, stability, and preclinical or clinical acceptability), polymorphism, etc. 

It is evident even to the casual observer that the vast majority of pharmaceutical products are administered as solid dosage forms, which are in turn produced by the formulation and processing of powdered solids. All too often characterization of raw materials and products has centered on aspects of chemical purity, with only passing attention being given to the physical properties of the solids. However, every pharmaceutical scientist knows of at least one instance in which a crisis arose due to some variation in the physical properties of input materials, and in which better characterization would have prevented the problem. 

In the present work, such a systematic approach to the physical characterization of pharmaceutical solids is outlined. Techniques available for the study of physical properties are classified as being associated with the molecular level (properties associated with individual molecules), the particulate level (properties pertaining to individual solid particles), and the bulk level (properties associated with an ensemble of particulates). Acquisition of this range of physical information yields a total profile of the pharmaceutical solid in question, whether it is an active drug, an excipient, or a blend of these. The development of a total profile is a requirement for successful manufacture of any solid dosage form. 

The dosage-form design is guided by the properties of the drug candidate. If an NCE does not have suitable physical and chemical properties or pharmacokinetic attributes, the development of a dosage form (product) may be difficult and may sometimes be even impossible. Any heroic measures to resolve issues related to physicochemical and biopharmaceutical properties of drug candidates add to the time and cost of drug... 

A new drug substance may exist in a multitude of crystalline and salt forms with different physical properties such as shape, melting point, and solubility that can profoundly impact the manufacturing and performance of its dosage form. 

Physical, chemical, and biological properties Dosage form, storage conditions, stability... 

For the pharmaceutical product development scientist, there is clearly a need for objective information about the practical performance of different excipients and their various grades. In this chapter we set out to bring together the results of some of our ongoing evaluations of the physical and mechanical properties of excipients commonly used for the manufacture of solid oral dosage forms. In this particular article, we have chosen to focus on the fillers that are most commonly used in the manufacture of immediate release tablets microcrystalline cellulose (MCC), lactose, calcium phosphate, and mannitol (1). 

Finally, knowledge of excipient mechanical and physical properties is essential to creating a robust formulation that manufactures tablets that meet specifications in a time- and material-efficient manner. Excipient selection must also take into consideration API stability and biopharmaceutical performance of the dosage form. Uneducated selection of excipients will likely lead to numerous formulating iterations that require much time and material, which are luxuries that product development scientists do not have in the competitive pharmaceutical environment. 

An in vitro release rate can reflect the combined effect of several physical and chemical parameters, including solubility and particle size of the active ingredient and rheological properties of the dosage form. In most cases, in vitro release rate is a useful test to assess product sameness between prechange and postchange products. However, there may be instances where it is not suitable for this purpose. In such cases, other physical and chemical tests to be used as measures of sameness should be proposed and discussed with the Agency. With any test, the metrics and statistical approaches to documentation of sameness in quality attributes should be considered. 

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