Formula Design for Hard Capsules-II

The formula and technology for capsule filling

Excipient selection is another necessary subject in formula design. The upstream processes of capsule production include material handling (such as grinding), granulating (wet, dry or fluid bed granulating) and mixing, etc.. The most notable difference in these process lies in granulating API or not.

In 1990s. a survey showed that direct powder filling was the top priority for about 46% factories during capsule research and development. What’s interesting is that in afterward practical production, direct powder filling accounted for only 0-10% in over half the factories. This reflects that direct powder filling is actually challenging in practical production. But in recent years, direct powder filling or powder compression becomes feasible with the improvement of technologies, new excipients and equipment. More and more preparations are produced by these technologies. These techniques also become effective in making sure fast launch of new drugs, especially for the factories which spare no efforts in new drug research and development.

Granulation technology for the capsule filling

Granulation, on the other hand, can effectively better poor properties of API, including increase its density, improving its fluidity and compressibility and reducing its adhesion during production. Besides, granulation can raise stability and quality of both production and products. Furthermore, compared with dry granulation, wet granulation functions more. It can facilitate drug dissolution and mix raw material more uniformly. In fact, some investigations also shows that during capsule development, about 64% factories prefer to process material by wet granulating.

However, even though material is granulated, excipients will be additionally included into the capsule formula for better technique feasibility, which also caused higher complexity.

The dosing method one capsule filling machine

Nowadays, capsule filling machines meter material mainly with metering cup or metering plate. But in general, capsule filling can be described in the following process in detail: 1) metering powder in certain volume or weight, 2) compressing the powder into column shape, 3) filling the powder column to shells, and 4) locking the shells. The material to be filled should be of proper fluidity, lubricity and compressibility. First of all, the fluidity guarantees smooth conveying and accurate metering of the material. But it doesn’t suggest that material of better fluidity can have better performance in capsule filling. Generally speaking, the material, whose Carr Index is between 20-30%, can adapt to the filling machines well. Next, material of certain lubricity will not adhere so that shells can be locked easily. Finally, good compressibility refers to that the material can be compressed to powder column of appropriate strength. As a result, less powder will leak during material shifting and shell locking to uniform capsule weights.