scholarly journals Direct Cyclodextrin Based Powder Extrusion 3D Printing for One-step Production of the BCS Class II Model Drug Niclosamide

Author(s):  
Monica Pistone ◽  
Giuseppe Francesco Racaniello ◽  
Ilaria Arduino ◽  
Valentino Laquintana ◽  
Antonio Lopalco ◽  
...  

Abstract Niclosamide (NCS) is a drug that has been used as an anthelmintic and anti-parasitic active principle for about 40 years. Recently, some studies have highlighted its potential in treating various tumors, allowing a repositioning of this drug. Despite its potential, NCS is a Biopharmaceutical Classification System (BCS) Class II drug, and is consequently characterised by low aqueous solubility, poor dissolution rate and reduced bioavailability, which limits its applicability. In this work, we utilize a very novel technique, Direct Powder Extrusion (DPE) 3D printing, which overcomes the limitations of previously used techniques (Fused Deposition Modelling, FDM) to achieve direct extrusion of pharmaceutical grade powder mixtures consisting of NCS, hydroxypropyl methylcellulose (HPMC, Affinisol 15 LV), hydroxypropyl-b-cyclodextrin (HP-β-CD) and polyethylene glycol (PEG) 6000. For the first time, direct printing of powder blends containing HP-β-CD was explored. For all tablets, in vitro dissolution studies showed sustained drug release over 48 hours, but for tablets containing HP-β-CD, the release was faster. Solid-state characterisation studies showed that during extrusion, the drug lost its crystal structure and was evenly distributed within the polymer matrix. All printed tablets exhibited good mechanical and physical features and guarantee stability of the drug content for up to 3 months. This innovative printing technique has demonstrated the possibility to produce personalised pharmaceutical dosage forms starting directly from powders, avoiding the use of filament used by FDM.

2020 ◽  
Vol 1 (2) ◽  
pp. 55
Author(s):  
Dyah Hikmawati ◽  
Sarda Nugraheni ◽  
Aminatun Aminatun

3D printing technology application in tissue engineering could be provided by designing geometrical scaffold architecture which also functionates as drug delivery. For drug delivery scaffold on bone tuberculosis, the cell pore of the geometric design was filled with Injectable Bone Substitutes (IBS) which had streptomycin as anti-tuberculosis. In this study, scaffolds were synthesized in three cells geometric filled by Injectable Bone Substitutes (IBS), Hexahedron, Truccated Hexahedron, and Rhombicuboctahedron, which had 2.5 mm x 2.5 mm x 2.5 mm size dimension and 0.8 mm strut. The final design was printed in 3D with polylactic acid (PLA) filament using the FDM process (Fused Deposition Modelling). The composition of IBS paste was a mixture of hydroxyapatite (HA) and gelatine (GEL) 20% w/v with a ratio of 60:40, streptomycin 10 wt% and hydroxypropyl methylcellulose (HPMC) 4% w/v. It was then characterized using Fourier-transform infrared spectroscopy (FTIR). Scaffold–paste characterization was included pore size test of 3D printing result before and after injected using Scanning Electron Microscope SEM, porosity test, and compressive strength test. The result showed that the pore of scaffold design was 1379 µm and after injected with IBS paste, the pore leaving 231.04 µm of size. The scaffold with IBS paste porosity test showed ranges between 40,78-70,04% while the compressive strength of before and after injected ranges between 1,110-634 MPa and 2,217-6,971 MPa respectively. From the test results, the scaffold 3D printing with IBS paste in this study had suitable physical characteristics to be applicated on cancellous bones which were infected by tuberculosis.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1114
Author(s):  
Janine Boniatti ◽  
Patricija Januskaite ◽  
Laís B. da Fonseca ◽  
Alessandra L. Viçosa ◽  
Fábio C. Amendoeira ◽  
...  

For the last 40 years, praziquantel has been the standard treatment for schistosomiasis, a neglected parasitic disease affecting more than 250 million people worldwide. However, there is no suitable paediatric formulation on the market, leading to off-label use and the splitting of commercial tablets for adults. In this study, we use a recently available technology, direct powder extrusion (DPE) three-dimensional printing (3DP), to prepare paediatric Printlets™ (3D printed tablets) of amorphous solid dispersions of praziquantel with Kollidon® VA 64 and surfactants (Span™ 20 or Kolliphor® SLS). Printlets were successfully printed from both pellets and powders obtained from extrudates by hot melt extrusion (HME). In vitro dissolution studies showed a greater than four-fold increase in praziquantel release, due to the formation of amorphous solid dispersions. In vitro palatability data indicated that the printlets were in the range of praziquantel tolerability, highlighting the taste masking capabilities of this technology without the need for additional taste masking excipients. This work has demonstrated the possibility of 3D printing tablets using pellets or powder forms obtained by HME, avoiding the use of filaments in fused deposition modelling 3DP. Moreover, the main formulation hurdles of praziquantel, such as low drug solubility, inadequate taste, and high and variable dose requirements, can be overcome using this technology.


2020 ◽  
Vol 10 (5) ◽  
pp. 649-663
Author(s):  
Reena Siwach ◽  
Parijat Pandey ◽  
Harish Dureja

Background: The rate-limiting step in the oral absorption of BCS class II drugs is dissolution. Their low solubility is one of the major obstacles in the process of drug development. Dissolution rate can be increased by decreasing the particle size to the nano range, eventually leading to increased bioavailability. Objective: : In the present study, glimepiride loaded nanoparticles were prepared to enhance the dissolution rate. The aim of the work was to examine the effect of polymer-drug ratio, solvent-antisolvent ratio and speed of mixing on in vitro release of glimepiride. Methods: Glimepiride is an antidiabetic drug belonging to the BCS class II drugs. The polymeric nanoparticles were formulated according to Box-Behnken Design (BBD) using nanoprecipitation technique. The prepared nanoparticles were evaluated for in vitro drug release, loading capacity, entrapment efficiency, and percentage yield. Result: It was found that NP-8 has maximum in vitro drug release and was selected as an optimized batch. Analysis of Variance (ANOVA) was applied to the in vitro drug release to study the fitness and significance of the model. The batch NP-8 showed 70.34 ± 1.09% in vitro drug release in 0.1 N methanolic HCl and 92.02 ± 1.87% drug release in phosphate buffer pH 7.8. The release data revealed that the nanoparticles followed zero order kinetics. Conclusion: The study revealed that the incorporation of glimepiride into gelucire 50/13 resulted in enhanced dissolution rate.


Author(s):  
Sidra Nasir ◽  
Amjad Hussain ◽  
Nasir Abbas ◽  
Nadeem Irfan Bukhari ◽  
Fahad Hussain ◽  
...  
Keyword(s):  
Class Ii ◽  

2021 ◽  
Vol 11 (6) ◽  
pp. 2563
Author(s):  
Ivan Grgić ◽  
Vjekoslav Wertheimer ◽  
Mirko Karakašić ◽  
Željko Ivandić

Recent soft tissue studies have reported issues that occur during experimentation, such as the tissue slipping and rupturing during tensile loads, the lack of standard testing procedure and equipment, the necessity for existing laboratory equipment adaptation, etc. To overcome such issues and fulfil the need for the determination of the biomechanical properties of the human gracilis and the superficial third of the quadriceps tendons, 3D printed clamps with metric thread profile-based geometry were developed. The clamps’ geometry consists of a truncated pyramid pattern, which prevents the tendons from slipping and rupturing. The use of the thread application in the design of the clamp could be used in standard clamping development procedures, unlike in previously custom-made clamps. Fused deposition modeling (FDM) was used as a 3D printing technique, together with polylactic acid (PLA), which was used as a material for clamp printing. The design was confirmed and the experiments were conducted by using porcine and human tendons. The findings justify the usage of 3D printing technology for parts manufacturing in the case of tissue testing and establish independence from the existing machine clamp system, since it was possible to print clamps for each prepared specimen and thus reduce the time for experiment setup.


Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 203 ◽  
Author(s):  
Deck Tan ◽  
Mohammed Maniruzzaman ◽  
Ali Nokhodchi

Three-dimensional printing, also known as additive manufacturing, is a fabrication process whereby a 3D object is created layer-by-layer by depositing a feedstock material such as thermoplastic polymer. The 3D printing technology has been widely used for rapid prototyping and its interest as a fabrication method has grown significantly across many disciplines. The most common 3D printing technology is called the Fused Deposition Modelling (FDM) which utilises thermoplastic filaments as a starting material, then extrudes the material in sequential layers above its melting temperature to create a 3D object. These filaments can be fabricated using the Hot-Melt Extrusion (HME) technology. The advantage of using HME to manufacture polymer filaments for FDM printing is that a homogenous solid dispersion of two or more pharmaceutical excipients i.e., polymers can be made and a thermostable drug can even be introduced in the filament composition, which is otherwise impractical with any other techniques. By introducing HME techniques for 3D printing filament development can improve the bioavailability and solubility of drugs as well as sustain the drug release for a prolonged period of time. The latter is of particular interest when medical implants are considered via 3D printing. In recent years, there has been increasing interest in implementing a continuous manufacturing method on pharmaceutical products development and manufacture, in order to ensure high quality and efficacy with less batch-to-batch variations of the pharmaceutical products. The HME and FDM technology can be combined into one integrated continuous processing platform. This article reviews the working principle of Hot Melt Extrusion and Fused Deposition Modelling, and how these two technologies can be combined for the use of advanced pharmaceutical applications.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1524
Author(s):  
Sadikalmahdi Abdella ◽  
Souha H. Youssef ◽  
Franklin Afinjuomo ◽  
Yunmei Song ◽  
Paris Fouladian ◽  
...  

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.


2021 ◽  
Vol 9 ◽  
Author(s):  
Harald Rupp ◽  
Wolfgang H. Binder

Additive manufacturing has significantly changed polymer science and technology by engineering complex material shapes and compositions. With the advent of dynamic properties in polymeric materials as a fundamental principle to achieve, e.g., self-healing properties, the use of supramolecular chemistry as a tool for molecular ordering has become important. By adjusting molecular nanoscopic (supramolecular) bonds in polymers, rheological properties, immanent for 3D printing, can be adjusted, resulting in shape persistence and improved printing. We here review recent progress in the 3D printing of supramolecular polymers, with a focus on fused deposition modelling (FDM) to overcome some of its limitations still being present up to date and open perspectives for their application.


2021 ◽  
Vol 27 (3) ◽  
pp. 465-474
Author(s):  
Martin Krčma ◽  
David Škaroupka ◽  
Petr Vosynek ◽  
Tomáš Zikmund ◽  
Jozef Kaiser ◽  
...  

Purpose This paper aims to focus on the evaluation of a polymer concrete as a three-dimensional (3D) printing material. An associated company has developed plastic concrete made from reused unrecyclable plastic waste. Its intended use is as a construction material. Design/methodology/approach The concrete mix, called PolyBet, composed of polypropylene and glass sand, is printed by the fused deposition modelling process. The process of material and parameter selection is described. The mechanical properties of the filled material were compared to its cast state. Samples were made from castings and two different orientations of 3D-printed parts. Three-point flex tests were carried out, and the area of the break was examined. Computed tomography of the samples was carried out. Findings The influence of the 3D printing process on the material was evaluated. The mechanical performance of the longitudinal samples was close to the cast state. There was a difference in the failure mode between the states, with cast parts exhibiting a tougher behaviour, with fractures propagating in a stair-like manner. The 3D-printed samples exhibited high degrees of porosity. Originality/value The results suggest that the novel material is a good fit for 3D printing, with little to no degradation caused by the process. Layer adhesion was shown to be excellent, with negligible effect on the finished part for the longitudinal orientation. That means, if large-scale testing of buildability is successful, the material is a good fit for additive manufacturing of building components and other large-scale structures.


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