Fabrication of complex oral drug delivery forms by Three Dimensional Printing (tm)
Author(s)Katstra, Wendy E. (Wendy Ellen), 1974-
Massachusetts Institute of Technology. Dept. of Materials Science and Engineering.
Michael J. Cima.
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Three Dimensional Printing 3DPTM is a novel solid freeform fabrication technology that has been applied to the fabrication of complex pharmaceutical drug devices. Limitations of the technology as relating to pharmaceuticals have been addressed and prototype dosage forms have been fabricated. The resolution of the 3DP tablets was found to depend on particle size and liquid migration during printing and drying. The surface finish of 3DP tablets was enhanced by uniaxial pressing. Migration inhibiting additives were effective in limiting transport. Both aqueous and ethanol-based solutions showed a decrease in migration on the order of 20% when appropriate powder bed additives were introduced. Migration was also decreased by pre-printing barriers to confine secondary printed drug solutions. Low dosage forms were fabricated with as little as 2.3 nanograms. Lower dosages are expected upon dilution of the initial drug solution. Printing forms with high dosage is limited by powder void volume, filling efficiency, and drug solubility limits. Multiple print passes increased the dosage per tablet volume, 6, at the expense of process time. The use of drug suspensions to overcome solubility limits and uniaxial compression to reduce tablet volume was shown to significantly increase 6. The highest 8 achieved was 427 mg/cc for pressed suspension-printed tablets, representing 74% of the theoretical limit. Complex oral dosage forms were fabricated with 3DP to show lagged-release, extended-release, double-release, and zero-order-release. Release properties, such as lag time and release rate, were manipulated by varying the printing parameters.(cont.) Dual-release and zero-order-release forms were fabricated using a surface degradation/erosion system based on HPMC, lactose, and EudragitÊ¾ L100. Erosion rate constants were used to model release from tablets with non-uniform drug distributions. Diclofenac and chlorpheniramine dual-release tablets were designed with 3 drug regions, and dissolution of the tablets followed the model closely, exhibiting 2 onsets. Two types of zero-order tablets were invented and fabricated by 3DP. These contained drug concentration gradients designed to complement the volumetric nonuniformity of eroding shells. Three formulations showed constant release of diclofenac sodium over 1-7 hours (9.6mg/hr), 1-15 hours (6.8mg/hr), and 1-36 hours (2.5mg/hr).
Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2001.Includes bibliographical references (p. 237-241).
DepartmentMassachusetts Institute of Technology. Dept. of Materials Science and Engineering.
Massachusetts Institute of Technology
Materials Science and Engineering.