Abstract
Supercritical CO2 loading of preformed 3D printed drug carriers with active pharmaceutical ingredients (APIs) shows great potential in the development of oral dosage forms for future personalized medicine. We designed 3D printed scaffold like drug carriers with varying pore sizes made from polylactic acid (PLA) using a fused deposition modelling (FDM) 3D printer. The 3D printed drug carriers were then loaded with Ibuprofen as a model drug, employing the controlled particle deposition (CPD) process from supercritical CO2. Carriers with varying pore sizes (0.027–0.125 mm) were constructed and loaded with Ibuprofen to yield drug-loaded carriers with a total amount of 0.83–2.67 mg API (0.32–1.41% w/w). Dissolution studies of the carriers show a significantly decreasing dissolution rate with decreasing pore sizes with a mean dissolution time (MDT) of 8.7 min for the largest pore size and 128.2 min for the smallest pore size. The API dissolution mechanism from the carriers was determined to be Fickian diffusion from the non-soluble, non-swelling carriers. Using 3D printing in combination with the CPD process, we were able to develop dosage forms with individually tailored controlled drug release. The dissolution rate of our dosage forms can be easily adjusted to the individual needs by modifying the pore sizes of the 3D printed carriers.
Highlights
Supercritical fluid technology offers a wide range of opportunities in drug development and production due to its unique properties
For the micronization of poorly soluble active pharmaceutical ingredients, several processes based on supercritical fluids were developed [7], such as rapid expansion of supercritical solutions (RESS), where a supercritical fluid gets saturated with a substrate of interest following a sudden depressurization through a nozzle, which results in rapid precipitation of the solute [8]
The controlled particle deposition process (CPD) was developed, where a drug is dissolved in supercritical CO2 followed by penetration of the supercritical solution into the pores of the carrier and precipitation of the drug inside the pores by rapid pressure
Summary
Supercritical fluid technology offers a wide range of opportunities in drug development and production due to its unique properties. With a density near liquids and a viscosity near gases, supercritical CO2 shows excellent diffusivity and mass transfer capabilities [3,4] These properties can be utilized for extractions of plant materials, where the extractive power can be adjusted by controlling the pressure and temperature of the extraction system, which gives this technique an extra degree of freedom, compared to liquid extractions [3,5]. For the micronization of poorly soluble active pharmaceutical ingredients, several processes based on supercritical fluids were developed [7], such as rapid expansion of supercritical solutions (RESS), where a supercritical fluid gets saturated with a substrate of interest following a sudden depressurization through a nozzle, which results in rapid precipitation of the solute [8] Based on this process, the controlled particle deposition process (CPD) was developed, where a drug is dissolved in supercritical CO2 followed by penetration of the supercritical solution into the pores of the carrier and precipitation of the drug inside the pores by rapid pressure
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