scholarly journals Supercritical Fluid Technology for the Development of 3D Printed Controlled Drug Release Dosage Forms

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 543
Author(s):  
Johannes Schmid ◽  
Martin A. Wahl ◽  
Rolf Daniels
Keyword(s):  
Drug Release ◽  
Pore Size ◽  
Dissolution Rate ◽  
Supercritical Co2 ◽  
Controlled Drug Release ◽  
Drug Carriers ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Pore Sizes ◽  
3D Printed

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.

scholarly journals 3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1096
Author(s):  
Christos S. Katsiotis ◽  
Michelle Åhlén ◽  
Maria Strømme ◽  
Ken Welch
Keyword(s):  
Drug Release ◽  
Mesoporous Materials ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Great Promise ◽  
Poorly Soluble Drugs ◽  
Drug Concentrations ◽  
Poorly Soluble ◽  
3D Printed ◽  
Oral Dosage Forms

Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs.

scholarly journals 3D-Printed Isoniazid Tablets for the Treatment and Prevention of Tuberculosis—Personalized Dosing and Drug Release

2019 ◽  
Vol 20 (2) ◽  
Author(s):  
Heidi Öblom ◽  
Jiaxiang Zhang ◽  
Manjeet Pimparade ◽  
Isabell Speer ◽  
Maren Preis ◽  
...  
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Oral Drug Delivery ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Oral Drug ◽  
Fused Deposition ◽  
3D Printed ◽  
Hot Melt ◽  
Release Profiles

Abstract The aim of the present work was to produce 3D-printed oral dosage forms with a sufficient drug dose displaying various release profiles. Hot-melt extrusion was utilized to produce drug-loaded feedstock material that was subsequently 3D-printed into 6, 8, and 10 × 2.5 mm tablets with 15% and 90% infill levels. The prepared formulations contained 30% (w/w) isoniazid in combination with one or multiple pharmaceutical polymers possessing suitable properties for oral drug delivery. Thirteen formulations were successfully hot-melt extruded of which eight had properties suitable for fused deposition modeling 3D printing. Formulations containing HPC were found to be superior regarding printability in this study. Filaments with a breaking distance below 1.5 mm were observed to be too brittle to be fed into the printer. In addition, filaments with high moisture uptake at high relative humidity generally failed to be printable. Different release profiles for the 3D-printed tablets were obtained as a result of using different polymers in the printed formulations. For 8 mm tablets printed with 90% infill, 80% isoniazid release was observed between 40 and 852 min. Drug release characteristics could further be altered by changing the infill or the size of the printed tablets allowing personalization of the tablets. This study presents novel formulations containing isoniazid for prevention of latent tuberculosis and investigates 3D printing technology for personalized production of oral solid dosage forms enabling adjustable dose and drug release properties.

scholarly journals The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 393 ◽  
Author(s):  
Jannes van der Merwe ◽  
Jan Steenekamp ◽  
Dewald Steyn ◽  
Josias Hamman
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Drug Dissolution ◽  
Specific Reference ◽  
Dissolution Rates ◽  
Bioavailability Enhancement ◽  
Poor Solubility

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms. This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.

scholarly journals Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1872 ◽  
Author(s):  
Rishi Thakkar ◽  
Amit Raviraj Pillai ◽  
Jiaxiang Zhang ◽  
Yu Zhang ◽  
Vineet Kulkarni ◽  
...  
Keyword(s):  
Drug Release ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous State ◽  
Dosage Forms ◽  
Water Soluble ◽  
Patient Specific ◽  
3 Dimensional ◽  
Fused Deposition ◽  
3D Printed ◽  
The Impact

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

Toward quality assessment of 3D printed oral dosage forms

2018 ◽  
Vol 2 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Daniel Markl ◽  
Axel Zeitler ◽  
Thomas Rades ◽  
Jukka Rantanen ◽  
Johan Bøtker
Keyword(s):  
Quality Assessment ◽  
Dosage Forms ◽  
Oral Dosage ◽  
3D Printed ◽  
Oral Dosage Forms

scholarly journals Agglomerated Oral Dosage Forms of Artemisinin/β-Cyclodextrin Spray-Dried Primary Microparticles Showing Increased Dissolution Rate and Bioavailability

2013 ◽  
Vol 14 (3) ◽  
pp. 911-918 ◽  
Author(s):  
Anna Giulia Balducci ◽  
Enrico Magosso ◽  
Gaia Colombo ◽  
Fabio Sonvico ◽  
Nurzalina Abdul Karim Khan ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Oral Dosage Forms ◽  
Spray Dried
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