scholarly journals Customisable Tablet Printing: The Development of Multimaterial Hot Melt Inkjet 3D Printing to Produce Complex and Personalised Dosage Forms

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1679
Author(s):  
Anna Lion ◽  
Ricky D. Wildman ◽  
Morgan R. Alexander ◽  
Clive J. Roberts
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Inkjet Printing ◽  
Drug Loading ◽  
Dosage Forms ◽  
Drug Concentrations ◽  
Printing System ◽  
Dual Material ◽  
Drug Free ◽  
Hot Melt

One of the most striking characteristics of 3D printing is its capability to produce multi-material objects with complex geometry. In pharmaceutics this translates to the possibility of dosage forms with multi-drug loading, tailored dosing and release. We have developed a novel dual material hot-melt inkjet 3D printing system which allows for precisely controlled multi-material solvent free inkjet printing. This reduces the need for time-consuming exchanges of printable inks and expensive post processing steps. With this printer, we show the potential for design of printed dosage forms for tailored drug release, including single and multi-material complex 3D patterns with defined localised drug loading where a drug-free ink is used as a release-retarding barrier. For this, we used Compritol HD5 ATO (matrix material) and Fenofibrate (model drug) to prepare both drug-free and drug-loaded inks with drug concentrations varying between 5% and 30% (w/w). The printed constructs demonstrated the required physical properties and displayed immediate, extended, delayed and pulsatile drug release depending on drug localisation inside of the printed formulations. For the first time, this paper demonstrates that a commonly used pharmaceutical lipid, Compritol HD5 ATO, can be printed via hot-melt inkjet printing as single ink material, or in combination with a drug, without the need for additional solvents. Concurrently, this paper demonstrates the capabilities of dual material hot-melt inkjet 3D printing system to produce multi-material personalised solid dosage forms.

scholarly journals Development and Evaluation of Amorphous Oral Thin Films Using Solvent-Free Processes: Comparison between 3D Printing and Hot-Melt Extrusion Technologies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1613
Author(s):  
Jiaxiang Zhang ◽  
Anqi Lu ◽  
Rishi Thakkar ◽  
Yu Zhang ◽  
Mohammed Maniruzzaman
Keyword(s):  
Thin Films ◽  
3D Printing ◽  
Drug Release ◽  
Hot Melt Extrusion ◽  
Dosage Forms ◽  
Solvent Free ◽  
Melt Extrusion ◽  
Physico Chemical ◽  
3D Printed ◽  
Hot Melt

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of 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 Impact of Drug Loading Method on Drug Release from 3D-Printed Tablets Made from Filaments Fabricated by Hot-Melt Extrusion and Impregnation Processes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1607
Author(s):  
Kasitpong Thanawuth ◽  
Lalinthip Sutthapitaksakul ◽  
Srisuda Konthong ◽  
Supakij Suttiruengwong ◽  
Kampanart Huanbutta ◽  
...  
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Hot Melt Extrusion ◽  
Water Soluble ◽  
Melt Extrusion ◽  
Drug Content ◽  
Loading Method ◽  
Lower Drug ◽  
3D Printed ◽  
Hot Melt

The purpose of this study was to investigate the impact of the drug loading method on drug release from 3D-printed tablets. Filaments comprising a poorly water-soluble model drug, indomethacin (IND), and a polymer, polyvinyl alcohol (PVA), were prepared by hot-melt extrusion (HME) and compared with IND-loaded filaments prepared with an impregnation (IMP) process. The 3D-printed tablets were fabricated using a fused deposition modeling 3D printer. The filaments and 3D printed tablets were evaluated for their physicochemical properties, swelling and matrix erosion behaviors, drug content, and drug release. Physicochemical investigations revealed no drug–excipient interaction or degradation. IND-loaded PVA filaments produced by IMP had a low drug content and a rapid drug release. Filaments produced by HME with a lower drug content released the drug faster than those with a higher drug content. The drug content and drug release of 3D-printed tablets containing IND were similar to those of the filament results. Particularly, drug release was faster in 3D-printed tablets produced with filaments with lower drug content (both by IMP and HME). The drug release of 3D-printed tablets produced from HME filaments with higher drug content was extended to 24 h due to a swelling-erosion process. This study confirmed that the drug loading method has a substantial influence on drug content, which in turn has a significant effect on drug release. The results suggest that increasing the drug content in filaments might delay drug release from 3D-printed tablets, which may be used for developing dosage forms suited for personalized medicine.

scholarly journals Drug-Loaded Hydrogels for Intraocular Lenses with Prophylactic Action against Pseudophakic Cystoid Macular Edema

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 976
Author(s):  
Nadia Toffoletto ◽  
Madalena Salema-Oom ◽  
Soledad Anguiano Igea ◽  
Carmen Alvarez-Lorenzo ◽  
Benilde Saramago ◽  
...  
Keyword(s):  
Drug Release ◽  
Cataract Surgery ◽  
Macular Edema ◽  
Cystoid Macular Edema ◽  
Release Kinetics ◽  
Drug Loading ◽  
In Vitro Release ◽  
Intraocular Lenses ◽  
Therapeutic Drug ◽  
Drug Concentrations

Pseudophakic cystoid macular edema (PCME), caused by chronic inflammation, is the most common cause of visual impairment in the medium-term after cataract surgery. Therefore, the prophylactic topical administration of combined steroidal and non-steroidal anti-inflammatory drugs is commonly done. Drug-eluting intraocular lenses (IOLs) gained interest as an efficient way to overcome the compliance issues related to the use of ocular drops without the need for additional surgical steps. The incorporation of functional monomers and molecular imprinting were herein applied to design hydrogels suitable as IOLs and able to co-deliver steroidal (dexamethasone sodium phosphate) and non-steroidal (bromfenac sodium) drugs. The incorporation of N-(2-aminopropyl) methacrylamide (APMA) increased the drug uptake and improved the in vitro release kinetics. Imprinting with bromfenac resulted in a decreased drug release due to permanent drug bonding, while imprinting with dexamethasone increased the amount of dexamethasone released after dual-drug loading. The application of a mathematical model to predict the in vivo drug release behavior suggests the feasibility of achieving therapeutic drug concentrations of bromfenac and dexamethasone in the aqueous humor for about 2 and 8 weeks, respectively, which is compatible with the current topical prophylaxis after cataract surgery.

A Critical Review on 3D-printed Dosage Forms

2019 ◽  
Vol 24 (42) ◽  
pp. 4957-4978 ◽  
Author(s):  
Ilias El Aita ◽  
Hanna Ponsar ◽  
Julian Quodbach
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Critical Evaluation ◽  
Dosage Forms ◽  
Review Article ◽  
Current Status ◽  
Comprehensive Overview ◽  
Pharmaceutical Dosage Forms ◽  
Advantages And Disadvantages ◽  
Pharmaceutical Application

Background: In the last decades, 3D-printing has been investigated and used intensively in the field of tissue engineering, automotive and aerospace. With the first FDA approved printed medicinal product in 2015, the research on 3D-printing for pharmaceutical application has attracted the attention of pharmaceutical scientists. Due to its potential of fabricating complex structures and geometrics, it is a highly promising technology for manufacturing individualized dosage forms. In addition, it enables the fabrication of dosage forms with tailored drug release profiles. Objective: The aim of this review article is to give a comprehensive overview of the used 3D-printing techniques for pharmaceutical applications, including information about the required material, advantages and disadvantages of the respective technique. Methods: For the literature research, relevant keywords were identified and the literature was then thoroughly researched. Conclusion: The current status of 3D-printing as a manufacturing process for pharmaceutical dosage forms was highlighted in this review article. Moreover, this article presents a critical evaluation of 3D-printing to control the dose and drug release of printed dosage forms.

DLP 3D printing of Dexamethasoneincorporated PEGDA-based photopolymers: compressive properties and drug release

2020 ◽  
Vol 6 (3) ◽  
pp. 406-409
Author(s):  
Robert Mau ◽  
Thomas Reske ◽  
Thomas Eickner ◽  
Niels Grabow ◽  
Hermann Seitz
Keyword(s):  
Mechanical Properties ◽  
3D Printing ◽  
Drug Release ◽  
Drug Loading ◽  
Patient Specific ◽  
Burst Release ◽  
Compressive Properties ◽  
Drug Load ◽  
Polyethylene Glycol Diacrylate ◽  
3D Printed

AbstractPhotopolymerizing, high-resolution 3D printing methods such as Stereolithography (SLA) or Digital Light Processing (DLP) are very promising for the manufacturing of drug-incorporated, patient specific implants. However, a drug-load may be limited by adequately solubility of the active pharmaceutical ingredient (API) in the photopolymer. Furthermore, a drug-load may affect the mechanical properties of the material negatively. Here, we investigate the DLP 3D printing of drugincorporated photopolymers. Polyethylene glycol diacrylate (PEGDA, Mn = 700 g/mol) is used as matrix polymer and Dexamethasone (DEX) is used for drug-loading (10 g/L and 20 g/L). Compressive properties, drug release and drug stability of 3D printed test samples were analyzed. DEX was found to be sparingly soluble in the PEGDA-based photopolymer. Not all drug particles can be dissolved at a concentration of 20 g/L and a slurry-like suspension is formed. Drug-incorporated photopolymers of 10 g/L (solution) and 20 g/L (suspension) were processed successfully via DLP. The higher the drug-load, the lower the compressive strength. Mechanical properties can be improved via a post-curing in a UV light curing box. Drug-incorporated 3D printed test samples show burst-release of DEX. The post-curing process does not affect drug release. DEX degrades in 3D-printed test samples significantly (~ 30 %) over a several days time period.

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.

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