Paper presented at the 7th International Granulation Workshop. 1-3 July 2015, University of Sheffield, UK"This work aims to evaluate the usefulness of powdered milk as a vehicle of drugs for direct compression into mini-tablets specifically designed for the pediatric population.
A 23 full factorial design was carried out to identify the effect of selected variables and their interactions (paracetamol to milk ratio, fraction of disintegrant and compression force), on selected responses (weight variation, thickness and tensile strength of minitablets and dissolution time of paracetamol) of the mini-tablets. Tablets were manufactured according to a matrix design resulting in eight combinations of four different tableting formulations compacted at two distinct forces. Each batch of tablets was evaluated for thickness (n=6), uniformity of weight (n=20), diametric crushing strength and tensile strength (σ) (n=6) and dissolution testing (n=12). A stepwise multiple linear regression was used to identify and quantify the relationships between each response and the variables studied and their interactions. Results were analyzed by ANOVA to identify the significant variables and variable interactions responsible for the effects observed.The increase on milk fraction in the formulation improved the compressibility of paracetamol with a decrease on weight variation. Thinner and harder compacts with slower paracetamol releases were also obtained. These observations were not surprising if powdered milk composition is taken into consideration: milk proteins, lactose (widely used as diluent) and lipids (often used as binders, lubricants and taste masking agents), which individually or in combination contribute to easier the production of tablets. A marked decrease on the dissolution time was observed as sodium croscarmellose was added to the milk rich formulations, as anticipated. The increase of the compression force was reflected by the production of thinner compacts with slightly higher tensile strengths but little effect on the dissolution median time. At high forces it was often observed a higher crushing strength and an increase of the importance of particle deformation in disintegration time.The study has proved the viability of using powdered milk on the production of minitablets to the delivery of drugs. The experimental design and statistical analysis enabled the identification of the most significant variables and their interactions affecting the properties of the mini-tablets, particularly the milk/paracetamol ratio which proved to be critical for the proprieties of the final product."Fundação para a Ciência e Tecnologia (FCT
