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Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids

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Abstract

The existence of different solid-state forms such as polymorphs, solvates, hydrates, and amorphous form in pharmaceutical drug substances and excipients, along with their downstream consequences in drug products and biological systems, is well documented. Out of these solid states, amorphous systems have attracted considerable attention of formulation scientists for their specific advantages, and their presence, either by accident or design is known to incorporate distinct properties in the drug product. Identification of different solid-state forms is crucial to anticipate changes in the performance of the material upon storage and/or handling. Quantitative analysis of physical state is imperative from the viewpoint of both the manufacturing and the regulatory control aimed at assuring safety and efficacy of drug products. Numerous analytical techniques have been reported for the quantification of amorphous/crystalline phase, and implicit in all quantitative options are issues of accuracy, precision, and suitability. These quantitative techniques mainly vary in the properties evaluated, thus yielding divergent values of crystallinity for a given sample. The present review provides a compilation of the theoretical and practical aspects of existing techniques, thereby facilitating the selection of an appropriate technique to accomplish various objectives of quantification of amorphous systems.

Section snippets

INTRODUCTION

Once being an exclusive domain of ceramic and polymer science,1 glassy state is now extensively studied in diverse fields like basic physics, electronics, metallurgy, space research, food sciences,2 and pharmaceutical sciences.3,4 Vitrification or glass formation is the manner in which nature affords protection to organisms against harsh climatic conditions,5 the strategy mankind uses to preserve food stuffs,6 the means by which highly pure semiconductors and optics are prepared,7 and also the

NEED FOR QUANTIFICATION OF AMORPHOUS PHASE

The amorphous state can arise in three sets of circumstances: (i) the drug or excipient may be deliberately produced in an amorphous form to enhance product performance. The use of plasticizers, including water to lower the Tg of various cellulosic and acrylic polymers utilized in film coating and the use of spray-dried lactose and microcrystalline cellulose as direct compression excipients is an apt example of this.18 Other important examples of this strategy include the preparation of glassy

QUANTIFICATION TECHNIQUES

Over the years, various analytical techniques have been reported for quantifying amorphous or crystalline phase in solids. These techniques vary in their working principles, mechanical and thermal stress that is applied to the sample, time of analysis and amount of sample required, sensitivity of the technique to minute changes, and the necessity of internal or external standards.25 Numerous considerations are involved in the development of a good analytical method like sensitivity,

CONCLUSIONS

Over the past two decades, the increased usage of amorphous drugs as an approach to enhance solubility, coupled with the development of amorphous excipients for improved performance of dosage forms, has necessitated the development of efficient methods for characterization and quantification of the amorphous content. There are many precise and accurate methods suitable for characterizing amorphous pharmaceutical materials in all their configurations, including final dosage forms. As with any

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