Getting our fill… looking at the latest developments in coatings and capsules
Iñaki Bueno, formulation and manufacturing manager at Idifarma tells us more about the ins and outs, challenges, advantages and latest developments in coatings and capsules.
Q. What type of formulations are filled in a capsule?
A. In principle, any type of formulation may be dosed into hard capsules, from blends or granules, to coated pellets, to other oral dosage forms such as tablets, micro-tablets and smaller capsules. It is also possible to fill liquids, provided that the material of the capsule (generally gelatine, although there are other alternatives) is not soluble in the solvent employed in the formulation.
Q. How do you decide on capsule size and fill weight per capsule?
A. Once the formula of the contents of the capsule is developed and the weight to be dosed is known it is easy to define the most appropriate capsule size. The body of each size of capsule has a defined volume, so knowing the density of the mixture to fill we can establish the volume that will occupy the weight that we must fill in each capsule. In the case of mixtures (powder or granulate), knowing the tapped density makes it possible to determine the most suitable capsule size. For pellets or micro-tablets, where there is no possibility of compaction, it is necessary to use bulk density instead.
All capsule suppliers provide capsule size tables that facilitate the choice of capsule size.
Q. Are there differences when filling capsules for clinical studies versus commercial production?
A. There are no major differences, apart from the great potential that capsule filling provides for clinical trials, from filling just the API for first pre-clinical or clinical trials to filling other dosage forms in capsules (tablets or smaller-sized capsules, for instance) for blind or double-blind clinical trials.
Q. What are the challenges of capsule filling for liquid and powder formulations?
A. The main challenge when filling liquids in hard gelatine capsules is to find the right solvent, which does not interact with the capsule material. From a technological standpoint, the capsule filling machine requires a specific station to fill liquids, and the capsules must undergo an additional band sealing process to prevent leakage.
As far as powder filling is concerned, the main challenge is to achieve a formulation with good flow properties, which guarantees the correct filling of the dosing systems and therefore a good uniformity of mass of the contents of the capsule.
Q. What are the common things that can go wrong in capsule filling that manufacturers should be aware of?
A. Capsule filling is a complex process. It is very important that the product to be encapsulated is well developed, with an acceptable flow and a reproducible batch-to-batch density to avoid problems of mass uniformity.
In addition, an automatic encapsulating machine is very complex equipment and each capsule format is composed of numerous pieces, which must be perfectly aligned and adjusted to avoid the opening or breaking of capsules. When capsules are broken they can release their contents, staining the entire batch produced.
Finally, hard gelatine capsules eventually undergo a cross-linking reaction which renders the gelatine less soluble and may affect the release of the capsule contents.
Q. What are the advantages of soft gel capsules over other formulations?
A. The main advantage is given to the state in which the active ingredient is found. The fact that the active principle is dissolved in non-aqueous media can increase its bioavailability, something especially useful in case of low soluble molecules (BSC II and IV). Another benefit of having the API dissolved is that, for certain pharmaceutical products, this may contribute to a lower tmax, achieving the desired therapeutic effect in a shorter time.
Soft gel capsules have other advantages over other dosage forms: they are easier to swallow and aesthetically more pleasing.
Q. What are the reasons for including a coating?
A. Coating makes the tablet appear easier to swallow and aids in visual differentiation for the patient, thus reducing the potential risk of medication errors. Coating also reduces tablet friability and overcomes any damage or dusting issues often associated with uncoated tablets.
For a manufacturer coating helps to protect the tablet, provides a desired release profile, masks the taste of a bitter drug and minimises the impact that environmental conditions may have on drug stability. Commercially it aids packaging, extends the product shelf and helps differentiate the product.
Q. How important is choosing the correct coating?
A. When considering coating an oral solid dosage form, you need to consider the key aspects of the product’s core composition and how the coating can support and protect it while also creating an aesthetically pleasing tablet.
Choosing the right coating is very important, getting it ‘wrong’ can impact patient compliance or even compromise drug efficacy by negatively affecting the drug release profile.
Q. What are the latest developments in capsule production?
A. The latest developments are aimed at increasing the efficiency of processes to make rapid changes of formats and products and increase the flexibility to encapsulate different products (tablets, micro-tablets, pellets, liquids...) or various combinations of them inside capsules.
Q. How do these differ from traditional approaches and what are their benefits?
A. One of the main drivers is cost-efficiency, due to increasing competitiveness in the market. Also, novel combinations can benefit from advanced capsule filling technologies which enable the entrance in the market of drugs that might improve patient compliance.