Figure 1: Simplification of a manufacturing process using engineered excipients with direct-compression technology (API is
active pharmaceutical ingredient, DC is direct compression, WG is wet granulation, and RC is roller compaction).
Direct compression (DC) is a preferred manufacturing process as the continually modernizing pharmaceutical industry strives
to improve its manufacturing output while reducing operating costs (1, 2). Compared with wet-granulation technology, direct
compression offers the advantage of product stability, simplification of manufacturing process, and lower process cost (see
Figure 1) (3). The tableting blend for a DC process contains the active pharmaceutical ingredient (API), a filler, a binder,
a disintegrant, auxiliary excipients (e.g., glidants and solubilizers), and a lubricant. DC technology and the use of modern
tableting machines demand that the excipients and API form a compressible mixture with excellent flowability and a low tendency
of particle segregation.
Figure 2: Powder blend compressibility and flowability requirements for various tableting technologies (DC is direct compression,
WG is wet granulation, and RC is roller compaction).
The choice of tableting process is highly influenced by the flowability and compressibility of the API-excipient mixture (see
Figure 2) (1). The particle size/shape, density, moisture content, and composition of the excipients affect flowability and
compressibility, which ultimately drives the tableting process (see Figure 3) (4–9). Traditional excipients have limited ability
to provide flowability and compressibility in mixtures with cohesive and poorly flowable APIs. Tableting parameters, such
as equipment geometry and energy input add to the complexity of the DC system when dealing with multiparticulate powder systems
Figure 3: Critical performance parameters for excipients to be used in direct compression (DC). (LOD is loss on drying.)
To increase the use of direct compression in pharmaceutical tableting, novel excipients with enhanced flow and compressibility,
which can accommodate API variability, are needed. Nonetheless, this is not an easy task to achieve as the more compressible
a material is, the less flowable it will be. The most cost-effective methodology is to enhance certain functionality of an
existing excipient by using novel processing techniques, or synergistically combining it with other commonly used excipients.
For example, processing techniques, such as spray drying or granulation, have been used over time to improve microcrystalline
cellulose (MCC) properties. By using combinations of excipients classified as generally recognized as safe (GRAS) and innovative
processing techniques, particles can be engineered to provide desired properties for use in a DC process. The resulting engineered
excipients are commonly named "coprocessed," "high functionality," "multifunctional," or "performance" excipients. This new
class of excipients streamlines the process such that, in the end, the formulator will have the choice of preparing a DC blend
consisting of API, "coprocessed excipient," auxiliary excipients, and lubricant. This approach may be acceptable to the industry
and regulatory agencies because the novel excipients created are not considered new chemical entities (11).
The current status of high-functionality excipients has been reviewed in various articles (12–15). This class of excipients
should be very appealing to implementation in a pharmaceutical process governed by a quality-by-design (QbD) approach (16).
Based on QbD principles, the quality of the drug product is a function of drug substance, excipients and, manufacturing process;
thus using a performance excipient in a QbD formulation should simplify the scheme.
Taking into consideration the requirements of QbD and a DC process, a performance excipient, PanExcea MHC300G, based on MCC,
hydroxypropyl methylcellulose (HPMC), and crospovidone (CPVD), has been developed. The performance excipient was designed
to provide good flowability and compressibility by optimizing particle shape, size, porosity, density, composition, and surface
roughness (17–18). The objective of this paper is to evaluate the physical properties and functionalities of PanExcea MHC300G
and to correlate these properties with its performance in a high-speed tableting machine.