Pharmaceutical excipients are used in virtually all drug products and are essential for drug product manufacturing and performance. Thus, the successful manufacture of a robust product requires the use of well-defined excipients and manufacturing processes that consistently yield a quality product.
The intended end use of the excipient should be identified and considered in determining the appropriate regulatory and GMP requirements for the excipient and its manufacturing facility. However, the effects of excipient properties on the critical quality attributes (CQAs) of a drug product are unique for each formulation and process and may depend on properties of excipients.
An excipient may be used in different ways or for different purposes in a formulation and may therefore require different material attributes to achieve the desired performance. Thus the critical material attributes of the ingredients that must be identified and controlled to ensure the excipient performs its intended function in a drug product.
A critical material attribute (CMA) is a physical, chemical, biological, or microbiological property of a material that must be within an appropriate limit, range, or distribution to ensure that drug product CQAs are maintained throughout the product life cycle.
Most, but not all, CMAs become tests in a compendial monograph. In some applications, excipient suppliers and users will need to identify and control material attributes in addition to monograph specifications. Identification of CMAs requires a thorough understanding of drug product CQAs; the manufacturing process(es); and the physical, chemical, biological, or microbiological properties of each ingredient. Manufacturers should anticipate lot-to-lot and supplier-to-supplier variability in excipient properties and should have in place appropriate control measures to ensure that CMAs are maintained within the required limits.
CMAs of Pharmaceutical Excipients
The primary properties relevant to tablet and/or capsule excipients are those that can have a direct effect on formulation performance. These include:
1) Particle size and size distribution,
2) Particle shape,
3) Bulk/tapped/true density,
4) Specific surface area,
6) Moisture content,
7) Powder flow,
9) Crystal form, and
10) Compaction properties for tablet dosage forms.
Application of Pharmaceutical Excipients
Pharmaceutical excipients will be expected to provide various functions in the dosage form or it’s processing, including, but not limited to:
- Compression Aid
- Suspending/Dispersing Agent
- Coating/Film Former
- Identity through printing with ink
- Release Modifier
The use of excipients of multiple functionality in the formulation may result in simplification of the drug formulation design stage since there are fewer excipient suppliers to assess and monitor. The use of fewer excipients may simplify the manufacturing process at the small scale. However, scale up to commercial manufacture may require additional excipients not required in the initial formulation design studies.
An excipient used for the first time in a drug product or by a new route of administration is classified as new according to the ICH Guideline M4. There are a number of conditions set out by the US and European regulatory authorities to allow for its use.