Evaluation of the ability of powdered milk to produce minitablets containing paracetamol for the paediatric population

Abstract

The work aims at evaluating the usefulness of powdered milk as a drug matrix for the production of minitablets specifically designed for children. Mixtures made of powdered milk, paracetamol, mannitol, sodium croscarmellose and magnesium stearate (evaluated for flow properties, cohesiveness and caking tendency) were compacted into beams (evaluated for deformation, elasticity and stiffness) and minitablets (evaluated for uniformity of mass, thickness, tensile strength and paracetamol mean dissolution time) and a 2 3 factorial design performed. The increase on milk fraction in the formulation improved the compressibility of paracetamol and hardness of compacts, reducing weight variation and paracetamol release. A marked decrease on the dissolution time was observed as sodium croscarmellose was added to the milk rich formulations. The increase of the compression force resulted in the production of thinner compacts but had little effect on dissolution time. The production of beams has shown that deformation, bending strength and stiffness increased with both milk and compaction pressure, and decreased with sodium croscarmellose, whereas elasticity decreased when all variables increased. Tensile strength and mean dissolution time described minitablets well, unlike compaction force. The study has proved that powdered milk is suitable for the production of minitablets by direct compression of poor compressible drugs. Highlights-Powdered milk can be used as a matrix to deliver poorly compressible drugs.-Minitablets can be produced by direct compression of drug and powdered milk.-Materials' behaviour is different as powders, compacts or tablets.-The complexity of milk materials justifies unexpected outcomes for compacts and tablets.-Mean drug dissolution time was the most sensitive parameter to assess tablets' performance.

The Milky Way: paediatric milk-based dispersible tablets prepared by direct compression – a proof-of-concept study

“…Powdered skimmed milk was combined with unpleasant‐tasting active pharmaceutical ingredients (APIs), such as nitrazepam, in ratios ranging from 1 : 1 to 1 000 000 : 1 w/w (skimmed milk : API) to obtain taste masking, however, in association with sweeteners such as sorbitol and mannitol . Fewer studies have examined the material properties of powdered milk or infant formula . The compaction behaviour of the different milk types and infant formulae and hence suitability as potential excipients in dispersible tablets manufactured by direct compression is thus not well understood.…”

“…[18] Fewer studies have examined the material properties of powdered milk or infant formula. [22] The compaction behaviour of the different milk types and infant formulae and hence suitability as potential excipients in dispersible tablets manufactured by direct compression is thus not well understood.…”

In vitro Characterization and Evaluation of Commercialized Paracetamol Products in Jordan

“…The difference in paracetamol release profiles of the different products could be attributed to their composition and the method of manufacture (25)(26)(27). Immediate-release formulations usually contain variable excipients, such as diluent, glidant, antiadherent, disintegrant, superdisintegrants, and inorganic materials such as sodium bicarbonate.…”

Quantification of theophylline or paracetamol in milk matrices by high-performance liquid chromatography

“…Children's unique therapeutic needs have recently led to new pediatric regulations [4] , [5] and development of medicines specifically designed for this age group [6] , [7] . In this respect, milk has been proposed as a platform to deliver drugs in pediatrics [8] , [9] due to its lack of toxicity and acceptability by children. Milk components have also been used as vehicles for active drug ingredients [10] , [11] and nutraceuticals [12] .…”