Rats can predict aversiveness of Active Pharmaceutical Ingredients.

Taste is crucial for patient acceptability and compliance with prescribed medicines, in particular with pediatric patients. Evaluating the taste of new active pharmaceutical ingredients (APIs) is therefore essential to put in place adequate taste-masking techniques, if needed, which will lead to acceptable palatable formulations. Thus, there is an urgent need to develop and optimize taste assessment methods that could be used at different stages of the drug development process. The aim of this study was to investigate the suitability of the rat brief-access taste aversion (BATA) model as a screening tool for assessment of APIs aversiveness that could predict human taste responses. Presently, the taste intensity of nine marketed APIs known to have different levels of bitter intensity (quinine hydrochloride dihydrate, 6-n-propylthiouracil, sildenafil citrate, diclofenac sodium, ranitidine hydrochloride, caffeine citrate, isoniazid, telbivudine and paracetamol) was investigated at different overlapping concentrations with two in vivo taste assessment methods: the rat BATA model and human taste panels with the intention of determining the drugs' concentrations to produce half of the maximal rating. Overall there was a strong correlation (R2 = 0.896) between rats IC50 and humans EC50 values. This correlation verifies the BATA model as a rapid and reliable tool for quantitative assessment of API aversiveness. A comparable ranking order was obtained mainly for high and medium aversive compounds, whereas it was less aligned for weakly aversive compounds. It was nonetheless possible to propose a classification of poor taste intensity determined in rats that would predict human taste tolerability.

More than 5 years of European Paediatric Regulation: statistics and industrial experience.

The aim of the European paediatric legislation is to ensure high quality paediatric clinical research, and subsequently increase availability of authorised medicines that are appropriate for children and produce better information on medicines. One of the main pillars of the regulation is the paediatric investigation plan (PIP), a new key document in the general drug development process. PIP submission and approval are now mandatory to ensure registration of a new drug in the EU. A short summary of the achievements from the introduction of the regulation in 2007 is given. In addition, PIP case studies are presented to illustrate the challenges associated when working within the framework of the new process.

Playing hide and seek with poorly tasting paediatric medicines: do not forget the excipients.

The development of paediatric medicines can be challenging since this is a diverse patient population with specific needs. For example, the toxicity of excipients may differ in children compared to adults and children have different taste preferences. Acceptable palatability of oral paediatric medicinal products is of great importance to facilitate patient adherence. This has been recognised by regulatory authorities and so is becoming a key aspect of paediatric pharmaceutical development studies. Many active pharmaceutical ingredients (APIs) have aversive taste characteristics and so it is necessary to utilise taste masking techniques to improve the palatability of paediatric oral formulations. The aim of this review is to provide an overview of different approaches to taste masking APIs in paediatric oral dosage forms, with a focus on the tolerability of excipients used. In addition, where possible, the provision of examples of some marketed products is made.

Interlaboratory testing of Insent e-tongues.

The first interlaboratory testing of electronic taste sensing systems was performed within five participating centers, each working with the Insent (Insent Inc., Atsugi-Shi, Japan) e-tongue. Preparation of the samples for the comprised four experiments, shipping of the samples and evaluation of the results was performed at the University of Duesseldorf. The sensitivity (in this case the difference between lowest and highest sensor response) and slope of the regression line values, obtained within Experiment 1 and 2, have been found to serve as applicable evaluation criterions for interlaboratory comparability. Modified sensor responses could be attributed to aged sensors, but did not influence the results of either Experiment 3, dealing with the evaluation of film formulations, or Experiment 4, dealing with the evaluation of minitablet formulations, in a great amount. Presented PCA Score and Loading Scatter Plots as well as Euclidean distance patterns based on the raw sensor responses confirmed the comparable performance of Insent e-tongues of the participating centers.

Biodegradable polymers and their potential use in parenteral veterinary drug delivery systems.

Biodegradable polymers have been extensively studied for numerous drug delivery systems for human health purposes. The ever-increasing value of animals to human society allows the application of pharmaceutical developments in the veterinary field from those developed in human medicine. Although many similarities between the human and animal health industries exist there are also notable differences. This paper provides an insight into the animal health market with regard to the challenges and special considerations associated with veterinary drug delivery. It also gives an overview of biodegradable polymers that are used or have been tested in the veterinary field. The purpose of this paper is to highlight some recent developments in this area and to investigate the directions in which veterinary pharmaceutics is heading. In particular, examples of existing biodegradable veterinary drug delivery systems are presented together with applications including intravaginal devices, injectables and implantable systems.