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Technology of liquid filled hard capsules


Dr Milind Biyani, Director, Aspire Advisors, highlights on liquid filling process for automatic machines

Hard capsules enable filling liquid or semi-solids into hard capsules using liquid filling capsules machines. Two-piece hard capsules made of either gelatin or HPMC can be used for filling and band sealing non-aqueous liquid, paste, suspension, hot melts, and other vehicles that melt up to 70° C and flow easily (1). Filling of hard capsules is simpler, compact and economical process than soft gelatin capsules (SGC). Hard capsules have thinner walls and need overall four to five times lesser gelatin than SGC. It is not possible to fill hot melts in SGC. These can lose shape in topical and humid climates. Hard capsules reduce the exposure to oxygen and can be purged with Nitrogen. It also reduces product migration and odor into the shell.

The uniformity of liquid fill is in most cases better than powder filling machine (2). This is useful for low dose/potent drugs. During liquid filling there will be no dust generation which is helpful for formulation with toxic/irritant drugs. Materials which are liquid at room temperature present difficulties when formulating as dry powders, often requiring high concentrations of excipients to avoid processing problems. Fewer excipients are needed for liquid-filled formulations. Bioavailability of poorly water soluble drug can be significantly increased. Absorica (Isotretinoin capsules) was approved as 505(b)(2) product due to enhanced bioavailability. Hygroscopic drugs can also be handled using gelatin hard capsules (e g Vancomycin capsules) or HPMC hard capsules.

Recently, there has been a revival of interest in the filling of conventional two-piece hard capsules with semi-solids. The ability to fill the capsules on semiautomatic or automatic equipment is a recent development (2). Combination filling such as pellets, tablets and another capsule in addition to the liquid is possible with such machines. The Fluidocap 1000 is R&D scale semi-automatic machine that integrates the filling, closing and band sealing processes. The machine is fitted on a trolly. Output is up to 1000 capsules per hour.

The schematic presentation of the liquid filling process for automatic machines is described in the below figure.


For production scale machines, Fluidocap F20 and F40, output is 20,000 and 40,000 capsules per hour respectively with standard dosing equipment. With seal free dosing the output can go up to 35,000 and 60,000 capsules per hour for F20 and F40 respectively (3). There are minimal problems in the scale up to a production scale because increases in output are achieved by using multiples of dosing pumps.

The Fluidocap technology is the combination of various mechanisms and these systems include:

  • No Capsule No Fill (NCNF)
  • Seal free dosing block (optional)
  • Purging of filled capsules
  • Combination filling provisions
  • Industrial PC interface

Seal free dosing block advantages as compared to the standard are as follows:

  • Capable of processing high viscosity liquids
  • Eliminates cross contamination
  • Higher accuracy in fill weights
  • No-drip mechanism at stoppage
  • Easy to clean, hence maximising uptime
  • Higher and more assured productivity

Interchangeable nozzles of diameter 1, 1.5 and 2 mm are offered for filling liquids with different viscosities. Production scale machines are operated with servo motors for accuracy and fitted with ceramic dosing pumps to avoid cross contamination. Finer dose adjustment is done through HMI in steps of 0.1 mm. The hopper is equipped with variable speed stirrer as well as the maximum and minimum liquid level sensors.

If the viscosity of the liquid is low or if the formulation is mobile at ambient temperatures, the capsules will need to be sealed immediately after filling. One of the reasons that prevented the use of hard capsules for liquid-filling in past, was the propensity for leakage through the gap between the cap and body of the capsule (2). Proseal (3) is the new improved version of automatic band-sealing machine. In case of HPMC capsules, HPMC band sealing can be done. With speeds up to 70,000 capsules per hour, band sealing by Proseal provides benefits such as effective leakage prevention, FDA compliant tamper proof capsules, anti-counterfeiting, and improved shelf-life.

1. Milind Biyani, Choosing Capsules: A Primer, Pharmaceutical Technology, 41(10), 36-41, 2017.
2. Geoff Rowley, ” Filling of Liquids and Semi-solids into two piece hard capsules”, in Pharmaceutical Capsules, Ed. by Fridrun Podczeck, Brian E. Jones, Eds (Pharmaceutical Press, 2nd edn.,2004),
pp. 169-194.
3. production-scale/capsule-filling/fluidocap-sealing.php

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