Evaluation of new aroma substances for feline minitablet formulation

Abstract

Despite the global interest in companion animal pharmaceuticals, feline peroral medication still lacks tailor-made, palatable and voluntarily accepted pharmaceuticals with suitable size and attractive taste. As a consequence, treating cats with canine and even human pharmaceuticals has weakened patient compliance and treatment commitment, and has even left many pet cats untreated. In future, the companion animal pharmaceutical business will therefore particularly concentrate on cats and the rapid and economic development of palatable feline medication. Following this goal, the overall aim of this study was to facilitate voluntary drug administration to felines. Specifically we aimed to develop sophisticated and tailor-made feline pharmaceuticals, with the focus on flavours in minitablets. Since excipients should be easily obtained and suitable for formulation, we conducted rapid preformulation compatibility and stability screening tests of synthetic flavours with commonly used tableting excipients. On the basis of the feline carnivorous diet, L-methionine, L-leucine, L-proline and thiamine hydrochloride were presented as new aroma substances for the improvement of feline medication palatability. These flavours and a model substance for a bitter taste, denatonium benzoate, were systematically evaluated for their physicochemical properties, stability and physical compatibility. This was done with substances alone and in binary combinations of flavours and excipients. Stability and compatibility were examined employing DSC and XRPD. The results showed that L-proline and denatonium benzoate anhydrate were hygroscopic. Thiamine hydrochloride was incompatible with talc and sodium stearyl fumarate. The known incompatibility between the amines contained in aromas, and α-lactose monohydrate was used in assessing method sensitivity. Overall, the study provided new information on the compatibility of novel aromas with the tableting excipients. The study also demonstrated the applicability of XRPD and DSC in the rapid evaluation of instability and incompatibility.