Preparation and characterization of a powder manufactured by spray drying milk based formulations for the delivery of theophylline for pediatric use.

The study considered different fat content cow milks to deliver theophylline orally. Powders were obtained by spray drying theophylline dispersed in fresh milk according to a full factorial design of experiments. The correlation of the independent (milk fat content, skimmed to whole milk, theophylline fraction, and drying temperature) with the dependent (yield of the process and residual moisture content of the powder, particle size and distribution, density, surface polarity and theophylline content) variables enabled the construction of a mathematical model and a desirability function to predict the optimized levels of the variables. Good predictability was achieved for density, fairly good for yield, moisture content, surface polarity and yield whereas theophylline content and particle size were poorly predicted. Powders with up to 60% theophylline presented spherical (3.7 µm) and narrow sized distribution particles, with high density (1.6 g/cm-3) in high yields (>70%), stable for 6 month (25 °C/65%RH) in a closed container and for no longer than 2 day, after reconstitution in water due to bacteria growth (no pathogens) without signs of crystallinity. Preparations obtained with low fat milk were less stable than high fat content milk. Therefore, fresh milk can be transformed into stable powder compositions to prepare oral solid/liquid dosage forms to deliver individualized doses of theophylline.

Production and characterization of spray-dried theophylline powders prepared from fresh milk for potential use in paediatrics.

OBJECTIVE: This work evaluates the potential of using fresh milk to deliver theophylline to children. METHODS: Theophylline-fresh milk systems were prepared using different solids ratios (0 : 1-1 : 0) and three fat contents in commercial milks (low, medium and high), which were spray-dried at different inlet air temperatures (Tinlet - 105, 130 and 150 °C). The process was evaluated for yield and the resulting powders for moisture content (MC), particle size and shape, density and wettability. Theophylline-milk potential interactions (differential scanning calorimetry (DSC) and FT-IR) and chemical (theophylline content) and microbiological stability of powders (shelf and in-use) were also evaluated. KEY FINDINGS: The production yield (13.6-76.0%), MC (0.0-10.3%) and contact angles in water (77.29-93.51°) were significantly (P < 0.05) affected by Tinlet , but no differences were found concerning the mean particle size (3.0-4.3 µm) of the different powders. The milk fat content significantly (P < 0.05) impacted on the density (1.244-1.552 g/cm3 ). Theophylline content remained stable after 6 months of storage, before extemporaneous reconstitution. After reconstitution in water, low-fat milk samples (stored at 4 °C) met the microbial pharmacopoeia criteria for up to 7 days. No theophylline-milk components interaction was observed. CONCLUSION: Spray-dried milk-composed powders may be used as vehicles for theophylline delivery in paediatrics following further characterization and in-vivo evaluation.