Development of immediate release 3D-printed dosage forms for a poorly water-soluble drug by fused deposition modeling: Study of morphology, solid state and dissolution

Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

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3D Printing of Dapagliflozin Containing Self-Nanoemulsifying Tablets: Formulation Design and In Vitro Characterization

Pharmaceutics ◽

10.3390/pharmaceutics13070993 ◽

2021 ◽

Vol 13 (7) ◽

pp. 993

Author(s):

Mohammed S. Algahtani ◽

Abdul Aleem Mohammed ◽

Javed Ahmad ◽

M. M. Abdullah ◽

Ehab Saleh

Keyword(s):

3D Printing ◽

Solid Phase ◽

Immediate Release ◽

Water Soluble ◽

Solid Matrix ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

3D Printing Technique ◽

Poorly Water Soluble Drug

The 3D printing techniques have been explored extensively in recent years for pharmaceutical manufacturing and drug delivery applications. The current investigation aims to explore 3D printing for the design and development of a nanomedicine-based oral solid dosage form of a poorly water-soluble drug. A self-nanoemulsifying tablet formulation of dapagliflozin propanediol monohydrate was developed utilizing the semisolid pressure-assisted microsyringe (PAM) extrusion-based 3D printing technique. The developed formulation system consists of two major components (liquid and solid phase), which include oils (caproyl 90, octanoic acid) and co-surfactant (PEG 400) as liquid phase while surfactant (poloxamer 188) and solid matrix (PEG 6000) as solid-phase excipients that ultimately self-nanoemulsify as a drug encapsulated nanoemulsion system on contact with aqueous phase/gastrointestinal fluid. The droplet size distribution of the generated nanoemulsion from a self-nanoemulsifying 3D printed tablet was observed to be 104.7 ± 3.36 nm with polydispersity index 0.063 ± 0.024. The FT-IR analysis of the printed tablet revealed that no drug-excipients interactions were observed. The DSC and X-RD analysis of the printed tablet revealed that the loaded drug is molecularly dispersed in the crystal lattice of the tablet solid matrix and remains solubilized in the liquid phase of the printed tablet. SEM image of the drug-loaded self-nanoemulsifying tablets revealed that dapagliflozin propanediol monohydrate was completely encapsulated in the solid matrix of the printed tablet, which was further confirmed by SEM-EDS analysis. The in vitro dissolution profile of dapagliflozin-loaded self-nanoemulsifying tablet revealed an immediate-release drug profile for all three sizes (8 mm, 10 mm, and 12 mm) tablets, exhibiting >75.0% drug release within 20 min. Thus, this study has emphasized the capability of the PAM-based 3D printing technique to print a self-nanoemulsifying tablet dosage form with an immediate-release drug profile for poorly water-soluble drug.

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Roadmap to 3D-Printed Oral Pharmaceutical Dosage Forms: Feedstock Filament Properties and Characterization for Fused Deposition Modeling

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2018.11.012 ◽

2019 ◽

Vol 108 (1) ◽

pp. 26-35 ◽

Cited By ~ 33

Author(s):

Johanna Aho ◽

Johan Peter Bøtker ◽

Natalja Genina ◽

Magnus Edinger ◽

Lærke Arnfast ◽

...

Keyword(s):

Fused Deposition Modeling ◽

Dosage Forms ◽

Pharmaceutical Dosage Forms ◽

Fused Deposition ◽

Properties And Characterization ◽

Deposition Modeling ◽

3D Printed

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An Effective Technology for the Development of Immediate Release Solid Dosage Forms Containing Low-Dose Drug: Fused Deposition Modeling 3D Printing

Pharmaceutical Research ◽

10.1007/s11095-019-2655-y ◽

2019 ◽

Vol 36 (9) ◽

Cited By ~ 13

Author(s):

Hazal Ezgi Gültekin ◽

Serdar Tort ◽

Füsun Acartürk

Keyword(s):

3D Printing ◽

Fused Deposition Modeling ◽

Low Dose ◽

Immediate Release ◽

Dosage Forms ◽

Solid Dosage Forms ◽

Solid Dosage ◽

Fused Deposition ◽

Effective Technology ◽

Deposition Modeling

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Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing

Pharmaceutics ◽

10.3390/pharmaceutics12080692 ◽

2020 ◽

Vol 12 (8) ◽

pp. 692 ◽

Cited By ~ 2

Author(s):

Hui-Won Cho ◽

Seung-Hoon Baek ◽

Beom-Jin Lee ◽

Hyo-Eon Jin

Keyword(s):

3D Printing ◽

Water Soluble ◽

Poorly Water Soluble Drugs ◽

Fused Deposition ◽

Water Soluble Drug ◽

Single Process ◽

Water Soluble Drugs ◽

Poorly Water Soluble ◽

Hot Melt ◽

Poorly Water Soluble Drug

Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.

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Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol–polysorbate 80 solid dispersion carrier system

Journal of Pharmaceutical Sciences ◽

10.1002/jps.20044 ◽

2004 ◽

Vol 93 (5) ◽

pp. 1165-1175 ◽

Cited By ~ 74

Author(s):

Rose-Marie Dannenfelser ◽

Handan He ◽

Yatindra Joshi ◽

Simon Bateman ◽

Abu T.M. Serajuddin

Keyword(s):

Polyethylene Glycol ◽

Solid Dispersion ◽

Dosage Forms ◽

Water Soluble ◽

Polysorbate 80 ◽

Carrier System ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

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Development of Clinical Dosage Forms for a Poorly Water-Soluble Drug II: Formulation and Characterization of a Novel Solid Microemulsion Preconcentrate System for Oral Delivery of a Poorly Water-Soluble Drug

Journal of Pharmaceutical Sciences ◽

10.1002/jps.21547 ◽

2009 ◽

Vol 98 (5) ◽

pp. 1750-1764 ◽

Cited By ~ 36

Author(s):

Ping Li ◽

Sara R. Hynes ◽

Thomas F. Haefele ◽

Madhu Pudipeddi ◽

Alan E. Royce ◽

...

Keyword(s):

Oral Delivery ◽

Dosage Forms ◽

Water Soluble ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

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How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

Molecules ◽

10.3390/molecules26113106 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3106

Author(s):

Jolanta Pyteraf ◽

Witold Jamróz ◽

Mateusz Kurek ◽

Joanna Szafraniec-Szczęsny ◽

Daniel Kramarczyk ◽

...

Keyword(s):

Spatial Structure ◽

Fused Deposition Modeling ◽

Drug Loading ◽

Drug Dosage ◽

Dosage Forms ◽

Poly Vinyl Alcohol ◽

Single Filament ◽

Fused Deposition ◽

Deposition Modeling ◽

3D Printed

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.

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The Accuracy and the Printing Resolution Comparison of Different 3D Printing Technologies

Transactions on Aerospace Research ◽

10.2478/tar-2018-0023 ◽

2018 ◽

Vol 2018 (3) ◽

pp. 69-86 ◽

Cited By ~ 1

Author(s):

Ewelina Kluska ◽

Piotr Gruda ◽

Natalia Majca-Nowak

Keyword(s):

3D Printing ◽

Fused Deposition Modeling ◽

Selective Laser Sintering ◽

Water Soluble ◽

Optical Methods ◽

Fused Deposition ◽

Material Texture ◽

Deposition Modeling ◽

3D Printed ◽

Reference Specimens

Abstract The article presents a research conducted with the project: ‘Additive technology used in conduction with optical methods for rapid prototyping of 3D printed models’ [13]. In this article selected three different 3D printing technologies: Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS) and Material Jetting (MJ). Each of them was tested paying special attention to accuracy and resolution of printed elements. Accuracy tests were conducted on the reference specimens which also showed material texture. These specimens were scanned to verified dimensional deviations of printing methods. Printing resolution was verified on a heat exchanger model which was characterized by complicated structure. The highest accuracy and printing resolution was noticed in the MJ technology, PolyJet method on the Objet Eden 260 VS printing machine and the SUP 707 water soluble support material.

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