Objective: The possible application of a hot-melt ram extrusion printing to the preparation of diclofenac orodispersible films (ODF) made of maltodextrin was studied focusing the attention on the effects of taste-masking agents (i.e. namely mint, licorice-mint, and sucralose) and an opacifier (titanium dioxide [TiO2]).
Significance: This is a proof-of-concept of the feasibility to print ODF loaded with a thermosensitive drug substance by hot-melt technologies.
Methods: Diclofenac sodium (DNa) ODF made of maltodextrin (dextrose equivalent (DE) = 6 ) plasticized with glycerol were prepared by hot-melt extrusion printing. ODF were characterized for disintegration time, drug content, and solid state, in vitro dissolution in deionized water and simulated salivary fluid at pH 5.7, tensile, and adhesive properties. Moreover, the stability of ODF was assessed in accelerated conditions over six months.
Results: After the preparation, no variation in drug solid state was evident and the formation of impurity A of DNa was detected, even if it remained below the Pharmacopoeia (Ph. Eur.) limits (< 0.2%). Only the addition of DNa significantly improved the ODF tensile properties: the tensile strength increased from 0.17 ± 0.03 MPa (placebo ODF) to 2.21 ± 0.54 MPa (p ≤ 0.03). All ODF disintegrated in about 1 min, and the t80% was lower than 3 min. TiO2 reduced the static and dynamic peel forces (p ≤ 0.006) favoring the ODF detachment from the primary packaging material. During the accelerated stability study, ODF were easy to handle without fracture; the drug content, impurity A, and dissolution profiles remained superimposable.
Conclusion: Hot-melt printing can be suitable to prepare palatable ODF loaded with bitter thermosensitive drugs.
Keywords: Chemical stability; ODF; diclofenac; hot-melt; maltodextrins; pediatrics; printing; taste masking; tensile properties.