[CordenPharma Photo] High-speed manufacturing of tablets, the most popular and convenient oral dosage form.
Tablets – from powders to compacts
Tablets are currently the most widely used dosage form for oral drug delivery. This is not only due to their convenience and patient compliance, but also because of their popular characteristics such as precision dosing, scalability, and economy of manufacture.
It all starts as a powder; crystalline API is blended with carefully selected excipients and mixed into a homogeneous powder. This powder is then compacted, with or without additional processing steps, into tablets on a tablet press. The choice and selection of excipients and processes is of primordial importance, as it will define and influence how the process can be scaled and all the critical tablet attributes including content uniformity, weight, disintegration, dissolution, friability, and hardness. Most marketed tablets contain multiple excipients (e.g. 5 or more are very common), and each of them has a specific functionality.
The mechanics of what happens with a powder during compression are very complex. Applying pressure to a powder bed will ultimately lead to densification. This happens via spatial rearrangement of individual particles and plastic deformation, or a breaking down of the particles. This combination leads to multiple contacts between particles, resulting in attractive forces that keep the individual particles together to form a tablet. Hence it is obvious that the properties of compressed tablets are sensitive to both material characteristics and process parameters.
Important properties of tablets include hardness, which is a physical breaking force measurement, as well as disintegration and dissolution properties. Tablets need to remain intact when applying pressure on them, e.g., when they are pressed out of a blister. On the other hand, the dissolution behavior is linked to the porosity of the tablet. Microscopic voids in the tablet allow water to ingress into the tablet core to accelerate the disintegration and dissolution. Applying more compression pressure generally results in harder tablets, however this generally comes with a reduction of the porosity. Optimizing the overall properties of tablets is therefore a multivariate endeavor of finding the optimal process conditions and composition.
Making the right choices requires experience, know-how, and efficient processes. CordenPharma has long-standing experience in designing, developing, transferring, and scaling tableting processes.
Process understanding leads to robust processes
The dependency between applied pressure and the resulting key attributes is what needs to be understood. The United States Pharmacopeia, in its chapter USP <1062> (tablet compression characterization), provides the necessary definitions and terminology. To account for tablet shapes and sizes, values like tablet breaking force or applied compression force are normalized and are expressed as tensile strength and compression pressure, respectively.
- Tabletability describes the tensile strength as a function of compression pressure.
- Compressibility describes the solid fraction (another way to describe porosity) as a function of compression pressure.
- Compactibility describes the tensile strength as a function of solid fraction.
For a homogeneous powder blend, the tabletability, compressibility, and compactibility result in a unique profile. This is a very important point because, 1) this allows for the identification of the best compaction pressure range that will result in sufficient porosity, while obtaining sufficient hard tablets for the investigated powder blend, and 2) changes in physical attributes of powder blend constituents lead to different profiles. It is generally within the scope of process development and characterization to assess whether such attribute differences are to be considered critical or not.
Generating data to understand these characteristics provides the foundation for robust processing and successful scale-up. Having high-speed manufacturing for commercial purposes in mind, investigations of the influence of dwell time further strengthen the full understanding.
(CordenPharma Photo) Manufacturing of tablets on a rotary tablet press.
Compaction simulation: the use of a single punch instrumented tablet press for the most efficient process characterization
Nowadays compaction simulators allow the generation of such data with minimal quantities of material. A compaction simulator is generally a single punch tablet press that allows to simulate compression profiles as encountered in tablet presses of different brands. In addition, they are instrumented, which means sensors within the compaction simulator capture all necessary data like force and displacement of upper and lower punches as a function of time during the entire compression process, including the ejection from the die and the ejection force required to do so.
CordenPharma routinely uses a compaction simulator for the development and characterization of tableting processes. We have developed and implemented an efficient process to generate data with the smallest amount of material possible. The generated data provides process understanding that is needed for the implementation of robust processes at commercial speed and scale. Demonstrating process understanding is also an important aspect of any regulatory filing and helps to justify process parameters and settings.
(CordenPharma Photo) STYL’One Nano compaction simulator used for the
development and characterization of tableting processes at CordenPharma
CordenPharma is your partner of choice for OSD formulation development and manufacturing
We support you during the entire lifecycle of your products, from early phase development, clinical supplies, late-stage registration and validation to commercial manufacturing and packaging. This full-service capability includes early-phase formulation screening that considers biopharmaceutic principles, formulation development that considers compatibility, performance and scalability, and process development, transfer, and characterization to reach filing readiness. Our experts take care to bring your molecule from preclinical through all clinical phases to market. Additionally, we handle APIs with OELs down to the picogram per cubic meter level.
