Capsule (pharmacy) | EPFL Graph Search

In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are: Hard-shelled capsules, which contain dry, powdered ingredients or miniature pellets made by e.g. processes of extrusion or spheronization. These are made in two-halves: a smaller-diameter “body” that is filled and then sealed using a larger-diameter “cap”. Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil. Both of these classes of capsules are made from aqueous solutions of gelling agents, such as animal protein (mainly gelatin) or plant polysaccharides or their derivatives (such as carrageenans and modified forms of starch and cellulose). Other ingredients can be added to the gelling agent solution including plasticizers such as glycerin or sorbitol to decrease the capsule's hardness, coloring agents, preservatives, disintegrants, lubricants and surface treatment. Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication. For this reason, producers of drugs such as OTC analgesics wanting to emphasize the strength of their product developed the "caplet", a portmanteau of "capsule-shaped tablet", to tie this positive association to more efficiently-produced tablet pills, as well as being an easier-to-swallow shape than the usual disk-shaped tablet medication. In 1833, Mothes and Dublanc were granted a patent for a method to produce a single-piece gelatin capsule that was sealed with a drop of gelatin solution. They used individual iron molds for their process, filling the capsules individually with a medicine dropper. Later on, methods were developed that used sets of plates with pockets to form the capsules. Although some companies still use this method, the equipment is no longer produced commercially.

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, intravenous chemoreduction and focal therapy. Local administration routes of chemotherapy, intra-arterial (IAC) and intravitreal (IVC), have emerged as promising methods to salvage the eyes and vision. New improvements in the chemotherapy of RB are geared towards reducing side effects of the drugs employed. Emerging strategies includes alternative chemotherapeutic agents, drug combinations, and novel drug delivery systems. Most successful examples of drug repurposing so far have been serendipitous. The systematic approach here was identified candidate drugs by strategic high-throughput screening methods. In this thesis, hit drugs were screened from a drug library of primarily FDA-approved drugs, and the synergistic effect of selected drug combinations was investigated. The hit drug gemcitabine, known to be an effective clinical treatment for non-small cell lung cancers, in combination with carboplatin, was discovered to have the highest cytotoxicity of the hits identified, and appeared as a potential alternative therapeutic agent for RB treatment.Polymeric nanoparticles (NPs) as an improved drug delivery system were investigated with gemcitabine. The nanoprecipitation synthesis of a poly(lactic-co-glycolic acid), as known as PLGA, nanoparticle was developed for drug encapsulation. The characterization of PLGA NPs within various active pharmaceutical ingredients were studied using dynamic light scattering and scanning electron microscopy, revealing that spherical NPs ranging in size from 150 to 200 nm could be successfully prepared. The tumor cells proliferation inhibition was observed after treatment with this novel nanoformulation. Furthermore, the possibility of a dual drug delivery system was explored. Gemcitabine and carboplatin were encapsulated together in PLGA NPs and found to show a synergistic effect after dual drug release. Additionally, gemcitabine combined with the light-activated agent indocyanine green was prepared, and laser-induced photothermal therapy (PTT) was explored.

EPFL2022

Capsule recycling system for domestic coffee machines

Guglielmo Milan, Fernando Castañeda, Luca Massera

The system and method for used capsules (11), such as coffee capsules, with a lid and a capsule body, comprises at least cutting means (17) to cut the lid from the body, capturing means to extract the cut lid from the body, compacting means (12, 14) to compact the body of the capsule thereby extracting the coffee contained in said capsule and recuperating means (40, 41) to recuperate the coffee on one side and the cut lid with the compacted capsule body on the other side such that the materials are separated.

2018

Stem cell-based cardiovascular tissue engineering

Thomas Krähenbühl

Cardiovascular diseases, including myocardial infarction, are the leading cause of death worldwide for both men and women. Current therapies are limited by the restricted intrinsic regeneration capacity of the heart and by the lack of organs for transplantation. Human embryonic stem (hES) cells have the capacity to differentiate into various cell types, including vascular cells for forming de novo blood vessels to potentially repair the infarcted heart after myocardial infarction. Our goal was to improve cardiac function after myocardial infarction through hES-based cardiovascular tissue engineering. Our findings summarized: Improved cardiac performance, attenuated left ventricular dilation and decreased infarct size in infarcted rats can be attained after co-injection of hES-derived vascular cells and Thymosin β4 (Tβ4) in matrix metalloproteinase (MMP)-responsive hydrogels. Enhanced vascular cell adhesion, survival and organization can be achieved when coencapsulating bioactive peptide Tβ4 in MMP-responsive matrix in vitro. Directed cardiac differentiation of pluripotent cells can be influenced by matrix elasticity, adhesion ligand concentration and MMP-sensitivity in vitro. We first systematically modulated a three-dimensional (3D) MMP-responsive hydrogel, mimicking key biochemical characteristics of natural collagenous matrices, the major constituent of cardiac extracellular matrices. We found that these synthetic poly(ethylene glycol) (PEG)-based hydrogels can direct differentiation of pluripotent cardioprogenitors, using P19 embryonal carcinoma (EC) cells as a model, along a cardiac lineage in vitro. In order to systematically probe 3D matrix effects on P19 EC differentiation, matrix elasticity, MMP-sensitivity and the concentration of a matrix-bound RGDSP peptide, which is relevant in early cardiac developments were modulated. Soft matrices (E = 320 ± 64 Pa), mimicking the elasticity of embryonic cardiac tissue, increased the fraction of cells expressing the early cardiac transcription factor Nkx2.5 around 2-fold compared to embryoid bodies (EB) in suspension. In contrast, stiffer matrices (E = 4040 ± 420 Pa) decreased the number of Nkx2.5-positive cells significantly. Further indicators of cardiac maturation were promoted by ligation of integrins relevant in early cardiac development (α5β1, αvβ3) by the RGDSP ligand in combination with the MMP-sensitivity of the matrix, with a 6-fold increased amount of myosin heavy chain (MHC)-positive cells as compared to EB in suspension. This precisely controlled 3D culture system thus may serve as a potential alternative to natural matrices for engineering cardiac tissue structures for cell culture and potentially therapeutic applications. Neovascularization of infarcted tissue is a promising alternative strategy to potentially restoring lost contractile performance by cardiac cells. Vascular cells and cytokines are known to contribute to the protection of cardiomyocytes from death after myocardial infarction, but also in endogenous recruitment of vascular cells and even cardiomyocytes. The in vitro potential of the synthetic MMP-responsive PEG-hydrogel as a bioactive co-encapsulation system for vascular cells and a small bioactive peptide, Tβ4, was then examined. Tβ4 was previously shown to enhance survival of vascular cells and cardiomyocytes in ischemic environments, stimulate neovascularization after cardiac injury by inducing endogenous endothelial cell migration to the ischemic site, as well as play a key role in down-regulating expression of inflammatory molecules. We show that the physical incorporation of Tβ4 in this bioactive matrix creates a 3D environment conducive for human umbilical vein endothelial cell (HUVEC) adhesion, survival, migration and organization. Gels with entrapped Tβ4 increased the survival of HUVEC compared to gels without Tβ4 (p < 0.05), and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas the von Willebrand factor was significantly down-regulated (all p < 0.05). Incorporation of Tβ4 significantly increased MMP-2 and MMP-9 secretion of encapsulated HUVEC (p < 0.05). The gel acts as a controlled Tβ4-release system, as MMP-2 and MMP-9 enzymes trigger the release. In addition, Tβ4 facilitated HUVEC attachment and induced vascular-like network formation upon the PEG-hydrogels. These MMP-responsive PEG-hydrogels may thus serve as controlled co-encapsulation system of vascular cells and bioactive factors for in situ regeneration of ischemic tissues. Finally, we employed these injectable MMP-responsive bioactive hydrogels with vasculo-typic adhesion molecule as a provisional in situ reservoir of vascular cells derived from hES cells and Tβ4 peptide, in infarcted hearts. Typically, after myocardial infarction, the performance-generating contractile cardiac tissue is partially replaced by non-contractile fibrotic tissue, driven by upregulated enzymes such as MMP. Here, magnetic resonance imaging (MRI) revealed enhanced contractile performance 3 days and 6 weeks after myocardial infarction (both p < 0.001), attenuated left ventricular dilation (p < 0.05) and decreased infarct size at 6 weeks (p < 0.05) as compared to infarcted rats with PBS injection. . We found the gel substituting the native degrading extracellular matrix in the infarcted myocardium and promoting structural organization of endothelial cells and cardiomyocytes, while the delivered hES-derived vascular cells formed de novo capillaries in the infarct zone.

EPFL2009