Using Excipients In Powder Formulations

During the past few years, we've seen a growing interest in direct oral application products, evidenced by the large amount of products already available on the market. Of course, we can only speculate about the reasons, but I personally think it is mainly about line extensions of existing APIs — given that pipelines of new chemical entities (NCE) are drying. Orally disintegration tablets (ODTs) have become very popular and are the starting point into a generation of drug products where patient friendliness is the decisive criteria to gain share in a saturated market environment; however, sachets can be faster and easier compared with ODTs. In contrast to ODTs, sachets are also already dispersed and do not need a liquid for this first disintegration step. Meanwhile, consumers have also realised the benefits of sachets; for instance, stickpacks are very convenient and easy to use.

The EMA's regulation for paediatric formulations development, accompanied by concerns regarding preservatives in syrups for paediatric use, may also fortify the sachet trend. EC 1901/2006 came into force on 26 January 2007 to facilitate the development of ageappropriate dosage forms and is expected to increase the number of formulations for children. Concerns about the preservatives used in liquid formulations mean that these formulations will probably be developed in solid or dry forms. Considering that hospitals also often ask for dosage forms that enable easy administration for children, as well as the fact that children often have difficulties in swallowing tablets, sachets are a potential solution. Sachets may also beneficial when looking at compliance issues within geriatric patient groups. Direct oral applications mean you don't need water to dissolve the powder or swallow the tablet. Sachets also do not look like a pill — it's important not to underestimate the psychological effects associated with a dosage form!

Designing excipients for powder formulations

When designing and developing new excipients, we take all aspects of the finished dosage form into account and consumer expectations, such as taste, aftertaste and mouthfeel.

The physicochemical requirements of bulk exipients for solid dosage forms are clear. For powder formulations, however, it is mandatory that excipients also need to have a natural, sweet taste and the particles should have dissolution kinetics that create a pleasant mouthfeel, as well as a prolonged sweet release effect. These factors are very important from an end-user's point of view. Moreover, as the dosage form dissolves in the mouth and remains in the oral cavity during dissolution, the excipient must also be noncariogenic. To make the final product suitable for diabetic patient groups, the excipient should be low glycaemic too.

Looking at the processing side, the excipients' characteristics will always depend on the final product. When manufacturing a blend, for example, it is important for the excipient to have a particle size appropriate for manufacturing. Additionally, there should be virtually no dusting within production. When the powder dusts heavily you will encounter difficulties in sealing the sachets properly because the powder will stick to the seal. Manufacturers will then loose a certain amount of the powder, which disappears into the vacuum system.

One answer to the issues mentioned above is to use multifunctional excipients. These combine technical (physical and chemical) and sensorial properties; however, these are very recent on the market and are facing the challenge of replacing traditional excipients that have been used for years.

Another challenge in manufacturing powder formulations relates to equipment. The idea of sachets as direct oral application dosage form was originally developed in the confectionery sector and so is not new to many food manufacturers. Within the pharmaceutical sector, however, there is a time lag in implementing such a nonestablished processing technology because of regulatory issues and lack of experience, and we find that few manufacturers have the necessary equipment to fill sachets — in particular, you need flat pouch machines that enable the form, fill, weigh and seal of the sachet. One way of overcoming equipment needs, however, is to use a CMO.

Innovation

In my eyes, innovation in powder formulations is mainly about taste masking, aftertaste and mouthfeel. APIs can be very bitter and need to be taste-masked successfully to develop a palatable product. If the dissolution rate of the API cannot be affected, masking can be very challenging. There are basically two broad approaches to achieve this: creating a barrier between the taste bud and drug, or overwhelming the unpleasant taste. Flavour houses do a great job of developing technologies to mask the bitter taste of APIs and these developments can be regarded as real innovations in improving the market penetration of direct oral applications form. Also, excipient manufacturers have launched new products such as aqueous polymer coating materials that facilitate taste masking. Such coatings release the API at the right pH, but not its bitter taste in the oral cavity.

In the future, I think that sachet applications for the OTCmarket will emerge as a crossover between confectionery and pharma, which used to be absolutely contradictory. Pharmaceutical products have a rather clean appeal, but are associated with chemicals and illness, whereas the confectionery arena always tries to create a positive image by attracting consumers with new packaging, new ideas and positioning. Of course, you can't and shouldn't compare all pharmaceuticals with confectionery! However, when it comes to patient appropriateness, I personally think that manufacturers should think about adopting some ideas from the confectionary industry, including form, appeal and marketing. This could possibly be done with sachets. To do this, packaging will be decisive — packaging is the outer appearance of a product and thus gives the first impression. Nowadays, various ways of packaging are possible; for instance, packaging can improve shelf life and identification. Sachets reflect a rediscovered dosage form in the pharmaceutical sector and combine innovative packaging with attractive palatability, which can help improve patient compliance.

Today, new technical possibilities in terms of excipients and packaging concepts are available, and excipient manufacturers — particularly those who have experience in the confectionery market — are well prepared to serve the pharmaceutical industry with the products and concepts needed to facilitate the development of powder formulations. I believe that companies that can adapt manufacturing and marketing concepts fast will be able to gain a good market share.