Pharmaceutical Excipients

Properties, Functionality, and Applications in Research and Industry

Otilia M. Y. Koo, Otilia M. Y. Koo

• Publisher: Wiley
• Year: 2016
• ISBN:
  9781118992425
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

This book provides an overview of excipients, their functionalities in pharmaceutical dosage forms, regulation, and selection for pharmaceutical products formulation. It includes development, characterization methodology, applications, and up-to-date advances through the perspectives of excipients developers, users, and regulatory experts.

• Covers the sources, characterization, and harmonization of excipients: essential information for optimal excipients selection in pharmaceutical development
• Describes the physico-chemical properties and biological effects of excipients
• Discusses chemical classes, safety and toxicity, and formulation
• Addresses recent efforts in the standardization and harmonization of excipients

Chapter 1
Excipient Characterization

David Good and Yongmei Wu

Drug Product Science and Technology, Bristol-Myers Squibb Company, New Jersey, USA

1.1 Introduction

A comprehensive understanding of the chemical and physical properties of common pharmaceutical excipients is essential to the design of high-quality drug products that provide consistent performance. In many pharmaceutical formulations, the drug substance can be susceptible to chemical and physical changes induced by the properties of the bulk excipients [1]. This is often more pronounced for drug products where the ratio of excipient content to drug is very high (i.e., low drug loading formulations). In recent years, the regular advancement of highly potent and selective drug candidates has led to more formulations that are predominately comprised of excipients and incorporate lower levels of the active pharmaceutical ingredient (API). In addition, potent drug candidates often exhibit low aqueous solubility and can require enabling formulation technologies, which include unique excipients and/or processing steps, to provide the desired clinical exposure at some stage during the clinical development program [2]. These trends in drug substance properties as well as the implementation of quality by design (QbD) product development strategies place an increased emphasis on detailed characterization of excipients to achieve robust formulations and processes.

This chapter focuses on a fundamental description of the chemical and physical properties of excipients, the associated characterization methods, and implications for formulation and processing of drug products. Numerous publications such as USP monographs provide an introduction to basic compendial excipient test methods and properties. These compendial descriptions and methodologies serve the basis for classification and release testing of materials; however, additional characterization is often required in the selection and processing of excipients. The content presented in this chapter provides the reader an introduction to the current methodologies and excipient properties that are most significant for the development of a commercial drug product. Included in this chapter are detailed descriptions of excipient stability and impurities as well as material variability that can influence drug product performance. These considerations are essential to the successful preparation of dosage forms for preclinical and clinical development programs. As such, this material is valuable to all scientists and students involved in pharmaceutical research from the discovery to commercial formulation and manufacture stages.

1.2 Chemical and Physical Properties

There is extensive diversity in the chemical structural elements and physical properties of pharmaceutical excipients. Excipients can be categorized in common chemical classifications including inorganics (e.g., iron oxide as pigments, calcium phosphate as filler), small molecule organics and their salts (e.g., mannitol diluent/sweetener, sodium citrate alkalizing agent), as well as polymeric excipients that can be fully synthetic or naturally derived (e.g., hypromellose, starch). The diversity is further expanded by an abundance of natural product derivatives where feedstock variability (raw materials), isolation, and chemical processing can impact the purity and structural attributes. Table 1.1 provides an overview of several common functional and chemical classifications of excipients with USP monographs. In total, there are 230 excipient monographs available to formulators with published monographs in the Handbook of Pharmaceutical Excipients. Each monograph can represent numerous material grades (i.e., polymer molecular weight, degree of substitution, particle size distribution, morphology) and be available from multiple manufacturers. Alternate manufacturers often employ different synthetic schemes or isolation techniques that can result in slight differences in physical properties (i.e., melt temperature, crystallinity, loss on drying, particle size) and chemical profile (i.e., trace impurities). The methods of manufacture of excipients are often proprietary trade secrets and therefore it is incumbent on formulators to identify essential material property profiles of key excipients, which is reviewed later in this chapter. To generate this knowledge formulation scientists rely on numerous compendial excipient characterization methods and develop novel methods to analyze key quality materials attributes of a formulation.

Table 1.1 Examples of Excipients with Indication of Chemical Classification, Key Common Compendia Tests, and Other Specific Tests That Can Be Utilized by Manufacturers and Formulation Scientists

		Organic (Synthetic, Natural)		Key Characterization Methods
Excipient function	Inorganic	Small molecule	Polymeric	Compendial (Figure 1.1)	Others
Diluent	CaHPO4	Lactose, mannitol	Starch, cellulose (powdered or microcrystalline)	PSD: <429> LDS, sieving <786>, density, bulk, tap, true <616, 699>; <616>crystallinity; <731> LOD; water content <921>; SSA <846>; flow <1174>; Particle shape Particle size distri...

Table of contents

• Cover
• Title Page
• Copyright
• Table of Contents
• List of Contributors
• Chapter 1: Excipient Characterization
• Chapter 2: Excipients for Conventional Oral Solid Dosage Forms
• Chapter 3: Excipients and their Functionality for Enabling Technologies in Oral Dosage Forms
• Chapter 4: Excipients used in Biotechnology Products
• Chapter 5: Excipient Standards and Harmonization
• Chapter 6: Regulatory Information for Excipients
• Chapter 7: Development of New Excipients
• Chapter 8: PATability of Excipients
• Index
• End User License Agreement