3D printing of diclofenac orodispersible films

Introduction: Among the key quality attributes of orodispersible films (ODF), appropriate taste, acceptable appearance, and tensile properties suitable to guarantee handling without breakage, are of paramount importance. However, the use of taste masking agents (TMA) needs to be carefully studied as they may compromise the ODF tensile properties [1]. Nanosized materials, such as titanium dioxide (TiO2) often used to improve the aesthetic appearance of ODF, can also act as ODF nanofiller improving the mechanical properties [2]. Aim: This study reports the feasibility of printing ODF loaded with diclofenac sodium (DNa), TMA and TiO2 by hot-melt ram extrusion 3D printing [2]. DNa was selected as model since it is a bitter and thermosensitive drug. Materials and Methods: Maltodextrins with a dextrose equivalent of 6 (MDX) plasticized with glycerol was used as film forming material. ODF loaded with DNa, TMA (i.e. mint, licorice-mint and sucralose or a combination thereof [1]) and TiO2 were printed. ODF were characterized for thickness, disintegration time, drug content, in vitro dissolution in deionized water and pH 5.7 artificial saliva, tensile properties, and peel test. An accelerated stability study (40 °C, 75% RH) was also carried out over a period of 3 months. Results and Discussion: The adopted experimental conditions allowed printing of ODF with a thickness ranging from 220 to 300 μm which is suitable for patient’s handling. The addition of TiO2 improved the ODF appearance. ODF disintegrated within 80 s complying the Ph. Eur. specification. Superimposable in vitro dissolution profiles were obtained for drug loaded ODF with and without TMA in deionized water (t80%3 min); in artificial saliva, t80% was about 2 min for ODF containing TMA (p=0.001). The presence of DNa significantly increased the ODF tensile strength (2.21±0.54 MPa), compared to the tensile strength of the placebo ODF (0.17±0.03 MPa) (p≤0.03). Moreover, no significant change in the tensile strength was observed when the combination of the TMA were loaded in the DNa films. The presence of TiO2 lowered the static and dynamic peel forces (p≤0.006) required to remove the ODF from the primary packaging material. During the accelerated stability study, ODF remained non-sticky and easy to handle without fracture. Drug content was maintained within the allowed limits by the Ph. Eur., however, impurity A of DNa was detected below the Ph. Eur. limits (< 0.2%). The in vitro dissolution profiles were superimposable after 3 months. Conclusions: Hot-melt ram extrusion 3D printing can be proposed to prepare palatable ODF loaded with a thermosensitive bitter drug.