Comparison of the formulation requirements of dosator and dosing disc automatic capsule filling machines

Abstract

The overall objective of this study was to provide 'semi-quantitative' or 'rigorous' definitions of the fluidity, lubricity and compactibility requirements of formulation for representative dosator and dosing disc capsule filling machines. To that end, model formulations were developed for those properties using Carr's compressibility index, ejection force, and plug breaking force at a specified compression force to gauge fluidity, lubricity, and compactibility, respectively. These formulations were each encapsulated on an Hofliger-Karg GKF-400 dosing disc machine and a Zanasi LZ-64 dosator machine. Each machine was instrumented to measure plug compression and ejection forces. The encapsulation process was evaluated for %CV of fill-weight, ejection force, plug breaking force and the dissolution of marker drugs incorporated in the formulations. The f 2 metric was used to compare dissolution profiles. The results suggest: (1) formulations should meet different flow criteria for successful encapsulation on the two machines, (2) a relatively lower level of lubricant may be sufficient for the dosing disc machine, (3) a higher degree of formulation compactibility is needed for the dosator machine, and (4) transferring formulations between these machine types (same class, different subclass per FDA's SUPAC-IR/MR Manufacturing Equipment Addendum) could be challenging. In certain cases dissolution profiles for the same formulation filled on the two machines with equivalent compression force were different based on f 2 < 50. Overall, the results of this study suggest a range of formulation characteristics appropriate for transferring formulations between these two types of machines.

Lubrication potential of magnesium stearate studied on instrumented rotary tablet press

“…7 The "net work done" method using a texture analyzer (with a load cell of 50 kg, equivalent of 500 N) was employed to simulate the lubrication efficacy of MS for use in a tamping capsule-filling machine, where forces in the range of 100 to 200 N are involved. 8 The study had identified the best and the worst performers and related their performance to solidstate properties. Tableting, which requires application of much higher forces (in the range of 5-15 kN), can be divided into 2 distinct stages: initial compression (reduction in bulk volume because of displacement of gaseous phase) and consolidation (increase in mechanical strength because of cold welding and fusion bonding between the particles).…”

Rational design of powder formulations for tamp filling processes

“…Therefore, an optimum range of powder flow exists, above and below which fill weight uniformity will be poor. Heda et al (2002) suggested a Carr's index in the range 20±30%, whereas suggested a range of 15±30%.…”

“…However, fill weight uniformity can also be poor for free-flowing powders, as a result of powder flooding, leading to inconsistent filling of the dosing disk. In addition, powders with excellent flow properties may be difficult to compress, leading to weak plugs that Powder formulation design for tamp filling processes break on ejection (Heda et al 2002). Therefore, an optimum range of powder flow exists, above and below which fill weight uniformity will be poor.…”

“…A balance must be maintained between plug strength and ejection force, to maintain the integrity of the plug. Ejection forces have been found to increase for fine powders and at higher tamping forces (Small & Augsburger 1978;Heda et al 2002). Fine powders will have a greater surface area and thus an increase in the number of contact points with the wall of the dosing disk, resulting in higher ejection forces.…”

Investigation of various factors affecting encapsulation on the In-Cap automatic capsule-filling machine

“…[15][16] Yet others suggested the need for an optimum flow property as a requirement for low capsule weight variation. 13,17 The flow of powders is influenced by various factors including interparticle forces, surface irregularities, moisture, particle size, density, and particle shape. The use of any single flow test cannot account for all these factors 18 and a combination of flow tests is recommended.…”