Development of 3D printed mini-waffle shapes containing hydrocortisone for children's personalized medicine.

Hydrocortisone is mainly used in the substitution treatment of adrenal insufficiency which results in a dysregulation of cortisol. Compounding of hydrocortisone capsules remains the only low-dose oral treatment suitable for the pediatric population. However, capsules often show non-compliance in mass and content uniformity. Three-dimensional printing offers the prospect of practising personalized medicine for vulnerable patients like children. The goal of this work is to develop low-dose solid oral forms containing hydrocortisone by hot-melt extrusion coupled with fused deposition modeling for the pediatric population. Formulation, design and processes temperatures were optimized to produce printed forms with the desired characteristics. Red mini-waffle shapes containing drug loads of 2, 5 and 8 mg were successfully printed. This new 3D design allow to release more than 80 % of the drug in 45 min indicating a conventional release like the one obtained with capsules. Mass and content uniformity, hardness and friability tests complied with European Pharmacopeia specifications, despite the considerable challenge of the small dimensions of the forms. This study demonstrates that FDM can be used to produce innovative pediatric-friendly printed shapes of an advanced pharmaceutical quality to practice personalize medicine.

Soft tissue artifact causes significant errors in the calculation of joint angles and range of motion at the hip.

Soft tissue movement between reflective skin markers and underlying bone induces errors in gait analysis. These errors are known as soft tissue artifact (STA). Prior studies have not examined how STA affects hip joint angles and range of motion (ROM) during dynamic activities. Herein, we: 1) measured STA of skin markers on the pelvis and thigh during walking, hip abduction and hip rotation, 2) quantified errors in tracking the thigh, pelvis and hip joint angles/ROM, and 3) determined whether model constraints on hip joint degrees of freedom mitigated errors. Eleven asymptomatic young adults were imaged simultaneously with retroreflective skin markers (SM) and dual fluoroscopy (DF), an X-ray technique with sub-millimeter and sub-degree accuracy. STA, defined as the range of SM positions in the DF-measured bone anatomical frame, varied based on marker location, activity and subject. Considering all skin markers and activities, mean STA ranged from 0.3cm to 5.4cm. STA caused the hip joint angle tracked with SM to be 1.9° more extended, 0.6° more adducted, and 5.8° more internally rotated than the hip tracked with DF. ROM was reduced for SM measurements relative to DF, with the largest difference of 21.8° about the internal-external axis during hip rotation. Constraining the model did not consistently reduce angle errors. Our results indicate STA causes substantial errors, particularly for markers tracking the femur and during hip internal-external rotation. This study establishes the need for future research to develop methods minimizing STA of markers on the thigh and pelvis.