A New Era of Drug Products: Opportunities and Challenges

3D Printing of a Multi-Layered Polypill Containing Six Drugs Using a Novel Stereolithographic Method

Pharmaceutics ◽

10.3390/pharmaceutics11060274 ◽

2019 ◽

Vol 11 (6) ◽

pp. 274 ◽

Cited By ~ 48

Author(s):

Pamela Robles-Martinez ◽

Xiaoyan Xu ◽

Sarah J. Trenfield ◽

Atheer Awad ◽

Alvaro Goyanes ◽

...

Keyword(s):

3D Printing ◽

Three Dimensional ◽

Drug Distribution ◽

New Era ◽

Three Dimensional Printing ◽

Drug Products ◽

Dissolution Tests ◽

Material Fabrication ◽

First Time ◽

Dimensional Printing

Three-dimensional printing (3DP) has demonstrated great potential for multi-material fabrication because of its capability for printing bespoke and spatially separated material conformations. Such a concept could revolutionise the pharmaceutical industry, enabling the production of personalised, multi-layered drug products on demand. Here, we developed a novel stereolithographic (SLA) 3D printing method that, for the first time, can be used to fabricate multi-layer constructs (polypills) with variable drug content and/or shape. Using this technique, six drugs, including paracetamol, caffeine, naproxen, chloramphenicol, prednisolone and aspirin, were printed with different geometries and material compositions. Drug distribution was visualised using Raman microscopy, which showed that whilst separate layers were successfully printed, several of the drugs diffused across the layers depending on their amorphous or crystalline phase. The printed constructs demonstrated excellent physical properties and the different material inclusions enabled distinct drug release profiles of the six actives within dissolution tests. For the first time, this paper demonstrates the feasibility of SLA printing as an innovative platform for multi-drug therapy production, facilitating a new era of personalised polypills.

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Unbiased estimation of particle number and sizes using the new stereological tools: the disector, the fractionator, the selector, and the nucleator — or just point-sampled intercepts

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100104200 ◽

1988 ◽

Vol 46 ◽

pp. 428-429

Author(s):

H.J.G. Gundersen

Keyword(s):

Particle Number ◽

Small Distance ◽

Parallel Plane ◽

Unbiased Estimation ◽

Severe Problem ◽

New Era ◽

Size And Shape ◽

Distinct Property ◽

Sectioned Tissue

Previously, all stereological estimation of particle number and sizes were based on models and notoriously gave biased results, were very inefficient to use and difficult to justify. For all references to old methods and a direct comparison with unbiased methods see recent reviews.The publication in 1984 of the DISECTOR, the first unbiased stereological probe for sampling and counting 3—D objects irrespective of their size and shape, signalled the new era in stereology — and give rise to a number of remarkably simple and efficient techniques based on its distinct property: It is the only known way to obtain an unbiased sample of 3-D objects (cells, organelles, etc). The principle is simple: within a 2-D unbiased frame count or sample only cells which are not hit by a parallel plane at a known, small distance h.The area of the frame and h must be known, which might sometimes in itself be a problem, albeit usually a small one. A more severe problem may arise because these constants are known at the scale of the fixed, embedded and sectioned tissue which is often shrunken considerably.

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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