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A Q&A with BASF moderated by Patricia Van Arnum.
Tastemasking of solid dosage forms and liquid drugs is a challenge for pharmaceutical manufacturers. Most APIs are unpleasant or harsh tasting, which can lead to patient noncompliance. This challenge affects all age groups, but is specifically problematic for pediatric patients. Implementing tastemasking programs into the drug-manufacturing process is crucial to avoid losses due to noncompliance. Pharmaceutical manufacturers are faced with challenges in life-cycle management, cost control, global regulations, and patent protection. In a Q&A, Pharmaceutical Technology examines excipient selection and functionality in tastemasking applications.
In a webcast, Pharmaceutical Technology examined formulation development in product life-cycle management, including specialized formulations such as pediatric formulations, and related technical issues in excipient selection and functionality, including tastemasking and moisture protection, to develop an orally palatable product (1). Participating in the webcast were: Avinash Thombre, PhD, research fellow, pharmaceutical sciences with Pfizer Global Research and Development, who discussed life-cycle management and new dosage-form options; Karen C. Thompson, PhD, distinguished senior investigator, pharmaceutical sciences at Merck & Co., who discussed insight into pediatric formulations and related dosage forms; and Nigel Langley, PhD, MBA, head of North American technical sales, Pharma Ingredients & Services, BASF, who discussed novel tastemasking excipient solutions. For a perspective on excipient selection and functionality in tastemasking applications, Patricia Van Arnum, executive editor of Pharmaceutical Technology and moderator of the webcast further discussed these issues with BASF's Langley.
The dialogue was initiated following the launch by BASF of an excipient, Kollicoat Smartseal 30 D, an aqueous dispersion of a film-forming polymer with tastemasking and moisture-barrier applications for solid dosage forms. The product is a new coating polymer and is supplied as a 30% dispersion in water. From a product-characteristic perspective, the excipient is highly impermeable to water vapor, which helps preserve the potency of sensitive active ingredients. The polymer is stable in saliva and specifically soluble in gastric juice. These properties allow for effective protection from unpleasant taste in the patient's mouth and rapid release and onset of active-ingredient action in the stomach.
In October 2011, BASF and Colorcon formed a collaboration for developing future film-coating systems using BASF's Kollicoat Smartseal 30 D and a new Colorcon preformulated additive. Colorcon developed the preformulated additive system for use with Kollicoat Smartseal 30 D to enable efficient preparation and application of this polymer in tastemasking applications. The preformulated additive lowers the number of materials to be dispensed by 50% and reduces the preparation time by almost 40%, according to an Oct. 21, 2011, Colorcon press release.
Excipient properties in tastemasking
PharmTech: What characteristics does an excipient need to have to provide tastemasking?
Langley: The material has to be stable at pH 6.8 to 7.2, so you do not get any of the bitter drug released in the saliva. In addition, the drug has to, upon entering the stomach, be rapidly released at a low pH. We are basically looking for a reversed enteric polymer to provide that functionality. With respect to Kollicoat Smartseal 30 D, specifically, the polymer is insoluble at basic and neutral pH value and has very low vapor permeability, which is characterized by the structure—primarily, the two ethyl groups that are attached to the nitrogen moiety and the polymer itself is the methyl methacrylate diethylaminoethyl methacrylate copolymer. It is very insoluble at pH neutral values as well as basic pH. It forms a salt at pH values below 5.5, so the polymer dissolves quickly in the stomach releasing the drug.
Applications, performance, and examples
PharmTech: What are the applications for this excipient, how is it used to provide tastemasking, and what are some examples?
Langley: It has wide applicability, not only in tablet coatings, but also in pellet, particle, and crystal coatings. It is useful for orally disintegrating tablets, for tastemasking oral dispersibles, and also in granulation processes.
The recommendation of tablet-coating levels to provide tastemasking is between 2–5 mg/cm2, a little bit more is needed for moisture protection at 5–20 mg/cm2. Kollicoat Smartseal 30 D has very low water-vapor permeability. As a result, it is not plasticized by water. So, in coating, it is necessary to add a plasticizer in order to reduce the minimum film-forming temperature (~57 °C) to an acceptable level. Triethyl citrate and tributyl citrate are recommended for this purpose. In addition, an antioxidant, preferably butylated hydroxy toluene (BHT, 1–2.5 % based on polymer weight) is also required in the coating formulation.
A good tastemasking polymer would show no drug release at pH 6.8 to 7.2. And this is what Kollicoat Smartseal 30 D has been designed for. Let's compare different coating levels and the amount of drug release relative to the uncoated cores for the bitter drug, quinine hydrochloride. At coating levels between 4 mg/cm2 and 5 mg/cm2, there is no release of the drug at pH 6.8 to 7.2 during 60 min. When you reduce the pH to 1.2, you will see complete drug release, and this is an ideal situation for tastemasking.
PharmTech: What are other applications of the product?
Langley: Smartseal 30 D is also very suitable for pellet and crystal coatings. We believe that these applications increase in importance due to the rise of innovative dosage forms, such as orally dispersible tablets. For example, caffeine pellets can be effectively tastemasked at a coating level of 5 mg/cm2. Acetaminophen crystals are effectively tastemasked at 30 % weight gain where there is no drug release at pH 6.8 –7.2 during 120 min. Some tastemasking is achieved even as low as 7.5% weight gain. In each example, the pellet and crystal coating can be visualized by including a pigment in the formulation. Kollicoat Smartseal 30 D has an additional benefit as it provides gloss.
PharmTech: How do you evaluate tastemasking performance, and what are the key characteristics to achieve tastemasking?
Langley: Although it is good to show dissolution data, we really need to see it in reality whether you are achieving a tastemasking effect on the tablets themselves when you take them into your mouth. Using a professional panel for tastemasking is obviously important because they are trained to do just this exercise.
In our analysis, we [BASF] compared Kollicoat Smartseal 30D with the commercially available butylated methyl acrylate copolymer and hydroxypropyl methylcellulose products. At different coating levels, the panelists provided their assessments of bitter taste. For example, with the Kollicoat Smartseal 30D, at 5 mg/cm2, all the panelists reported a complete absence of bitter taste for quinine hydrochloride compared to the other materials tested. Hence, Kollicoat Smartseal 30 D is a very effective tastemasking polymer at that coating level.
In sum, Kollicoat Smartseal 30 D has extremely low water-vapor permeability, thereby providing the opportunity for moisture protection. It shows quick dissolution in acidic medium below pH 5.5 and a strong resistance at neutral pH. It is, therefore, deemed highly suitable for both tastemasking and moisture-protective coatings. One other advantage is it is an aqueous-based coating. No solvents are required. It has very low odor, and even more importantly, is not sticky, which can be a real advantage, especially on a manufacturing scale. It enables quick and simple preparation of the coating suspension. It has low viscosity and is easy to spray at high solids concentrations. It is effective at relatively low coating levels. Kollicoat Smartseal 30 D has been specifically designed to show exactly all of these characteristics to provide the solution the market was looking for. The result is tastemasking and moisture protection in combination with instant release and easy and economical film coating.
1. "Tastemasking in Formulation Development" Webcast, Pharm. Technol. Sept. 2011, http://pharmtech.com/fds, accessed Aug. 20, 2012.