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Which USP Chapter is the Most Important for Encapsulation?

pill capsules from encapsulator on table

In the tablet compression industry, we widely regarded USP Chapter <1062> as the one chapter that any R&D Scientist should be familiar with as they develop new formulations. This Chapter describes the relationship between a tablet’s compactibility, compressibility, tabletability, and manufacturability. But what about encapsulation? Capsule filling machines differ greatly from rotary tablet presses. There are new types defects to contend with, new terminologies to learn, different goals to achieve. They used primarily if USP <1062> for tablet compression, is there a similar piece of USP cornerstone content for capsules?

“Although the fundamental concepts described [in Chapter <1062>] are also applicable to other processes such as plug formation during encapsulation and roller compaction,” USP says, “the focus of [USP Chapter <1062>] is on tableting.” With those two topics in mind, we should examine chapters that deal with granulation, powder flowability, and other chapters that examine the density of powders, as they are the key factors in compressibility equations. Ultimately, USP Chapter <1174> should be the key focus for encapsulation applications. This blog article explores the correlation among USP Chapters <11764>, <699>, and <616>, since these chapters, taken together, address a common challenge found in both the tableting and encapsulation industries: flowability.

Which Challenge(s) do Tablets and Capsules Have in Common?

When developing a formulation that will be encapsulated, a powder or granulation needs to have the proper flowability of its powders to avoid issues like poor slug formation, as this can be a cause of capsule body dents. We have also written on ways to deal with other challenges such as sticking in capsules, however, this is from a manufacturing perspective. A solid understanding of USP chapters in the formulation stages (and even in pre-formulation, where Natoli Scientific help) can avoid these challenges early in the development process.

For shear cell testing specifically, one parameter that can be obtained that is also relevant to USP <1062> is tensile strength. At the core of an understanding of tensile strength is its relationship with density. This leads us into USP Chapter <699>. This USP chapter provides definitions of four types of density:

  1. True
  2. Pyncnometric
  3. Granular
  4. Bulk

USP defines true density as “the average mass per unit volume, exclusive of all voids that are not a fundamental part of the molecular packing arrangement.” True density is the denominator in calculating solid fraction, which itself is ultimately a measure of a powder’s bulk density and compressibility. More information on how to properly measure and address bulk density and compressibility is found in USP Chapter <616>.

Perhaps more relevant though is this Chapter’s attention given to Measures of Powder Compressibility. This refers to the Compressibility Index (using bulk and tapped volumes), and the Hausner Ratio. For more information on this, USP Chapter <1174> provides more details.

Although there are some variations in the method of determining the compressibility index and Hausner ratio, the basic procedure is to measure (1) the unsettled apparent volume, Vo, and (2) the final tapped volume, Vf, of the powder after tapping the material until no further volume changes occur (USP <1174>).

USP Chapter <1174> Powder Flow

“Because of the ability to more precisely calibrated and tested frequently using appropriate test control experimental parameters,” USP says, “flow properties can also be determined as a function of consolidation load, time, and other environmental conditions.” USP Chapter <1174> also makes reference to consolidation, which, USP says in their glossary in Chapter <1062>, is a synonym for compaction.

Regarding compressibility, a key factor in this is density, USP says: “…the compressibility index and Hausner ratio may be calculated using measured values for bulk density and tapped density.” To learn more about those chapters, USP Chapter <616> offers alternatives for procedural methods for measuring those types of densities. USP Chapter <1174> goes on to describe four other types of commonly reported methods for testing powder flows:

  1. angle of repose
  2. compressibility index or Hausner ratio
  3. flow rate through an orifice, and
  4. shear cell testing
tablet powder for tablet formulation
Angle of repose

Taken individually, these four methods are not enough to determine flowability since they do not provide enough data to make conclusions. In our experience, angle of repose, Carr index, and Hausner ratio are the only basic measurements. Therefore, we highly recommend using a Flodex in combination with this method. Visual observations from a Flodex will always give you a better chance for success. If you don’t have a powder flow tester, FT4 or otherwise, pay attention to the visual observations on a Flodex. Here are some questions you should be able to answer through your observations:

  • What does the angle of the powder bed left in the cup of the Flodex look like?
  • Does the powder left in the cup have an angle?
  • Did a cylinder shape form as the powder flowed through the orifice

Learn More with Your New Solid Dose Experts

In conclusion, when measuring powder flow, keep in mind as a general rule that the greater the angle, the less adhesive the powder. Though there are many ways to measure powder flow using instruments, formulas, indices, etc. A complete understanding of this practice comes from knowing the correlation between USP Chapters. When developing formulations for capsules, the three we suggest starting with are USP Chapters <1174>, <699>, and <616>.

Navigating these chapters can be difficult. Working with an expert who knows them proficiently can save untold amounts of time and cost. Natoli Scientific is your solid dose expert. Want to experience what working with us is like? Contact us today, or if you’re still exploring options, check out our free webinar on Characterizing Powders, Granules Ribbons and Tablets by Surface Area, Pore Size and Density, hosted by Dr. Martin Thomas of Anton-Paar. This webinar explores the characterization of various solid forms with reference to appropriate USP chapters mentioned above, as well as Chapters <267> Porosimetry by Mercury Intrusion and <846> Specific Surface Area.

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