Manufacturing processes
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BACKGROUND AND AIM: Digital technology is becoming more accessible for common use in medical applications; however, their expansion in prosthetic and orthotic laboratories is not large because of the persistent image of difficult applicability to real patients. This article aims to offer real example in the area of human facial prostheses. TECHNIQUE: This article describes the utilization of optical digitization, computational modelling, rapid prototyping, mould fabrication and manufacturing of a nasal silicone prosthesis. This technical note defines the key points of the methodology and aspires to contribute to the introduction of a certified manufacturing procedure. DISCUSSION: The results show that the used technologies reduce the manufacturing time, reflect patient's requirements and allow the manufacture of high-quality prostheses for missing facial asymmetric parts. The methodology provides a good position for further development issues and is usable for clinical practice. Clinical relevance Utilization of digital technologies in facial prosthesis manufacturing process can be a good contribution for higher patient comfort and higher production efficiency but with higher initial investment and demands for experience with software tools.
- MeSH
- design s pomocí počítače trendy MeSH
- elektronický nos trendy MeSH
- lidé MeSH
- obličej anatomie a histologie MeSH
- počítačová simulace MeSH
- počítačové zpracování obrazu metody trendy MeSH
- protézy - design MeSH
- protézy a implantáty trendy MeSH
- silikony MeSH
- vynálezy trendy MeSH
- zobrazování trojrozměrné MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Despite the efficacy and potential therapeutic benefits that poly(lactic-co-glycolic acid) (PLGA) nanomedicine formulations can offer, challenges related to large-scale processing hamper their clinical and commercial development. Major hurdles for the launch of a polymeric nanocarrier product on the market are batch-to-batch variations and lack of product consistency in scale-up manufacturing. Therefore, a scalable and robust manufacturing technique that allows for the transfer of nanomedicine production from the benchtop to an industrial scale is highly desirable. Downstream processes for purification, concentration, and storage of the nanomedicine formulations are equally indispensable. Here, we develop an inline sonication process for the production of polymeric PLGA nanomedicines at the industrial scale. The process and formulation parameters are optimized to obtain PLGA nanoparticles with a mean diameter of 150 ± 50 nm and a small polydispersity index (PDI < 0.2). Downstream processes based on tangential flow filtration (TFF) technology and lyophilization for the washing, concentration, and storage of formulations are also established and discussed. Using the developed manufacturing and downstream processing technologies, production of two PLGA nanoformulations encasing ritonavir and celecoxib was achieved at 84 g/h rate. As a measure of actual drug content, encapsulation efficiencies of 49.5 ± 3.2% and 80.3 ± 0.9% were achieved for ritonavir and celecoxib, respectively. When operated in-series, inline sonication and TFF can be adapted for fully continuous, industrial-scale processing of PLGA-based nanomedicines.
- Publikační typ
- časopisecké články MeSH
8, 89 s. : il.
Public Health Service publication ; no. 999
8, 127 s. : il.
Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes. The present work reports a successful transfer of an existing drug product from batch to continuous manufacturing process without changing the formulation. A key step was continuous powder blending, whose design and operating parameters including weir type, agitation rate, dynamic hold-up and residence time were systematically investigated with respect to process repeatability. A NIR-based multivariate data model for in-line composition monitoring has been developed and validated against an existing quality control method for measuring tablet content uniformity. A continuous manufacturing long-run with a throughput of 30 kg/h (approx. 128,000 tablets per hour), uninterrupted for 320 min, has been performed to test and validate the multivariate data model as well as the batch to continuous process transfer. The final disintegration and dissolution properties of tablets manufactured by the continuous process were found to be equivalent to those manufactured by the original batch process.
- MeSH
- blízká infračervená spektroskopie metody MeSH
- farmaceutická chemie metody MeSH
- farmaceutická technologie * metody MeSH
- pomocné látky chemie MeSH
- prášky, zásypy, pudry chemie MeSH
- příprava léků metody MeSH
- řízení kvality MeSH
- rozpustnost MeSH
- tablety * MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
In the last decade, pharmaceutical regulatory agencies are focused on monitoring and evaluation of trace-level genotoxic impurities (GTIs) in drug substances, which requires manufacturers to deliver innovative approaches for their analysis and control. GTIs in the low p.p.m. level rising from the process of drug production have to be positively identified and quantified. Therefore, sensitive and selective analytical methods are necessary for required quantification level of these GTIs. Unfortunately, general guidance on how to develop strategy of the analysis and control of GTIs is currently missing in the pharmaceutical industry. Therefore, practical example of the analytical control of 2-chloro-N-(2-chloroethyl)ethanamine GTI in the vortioxetine (VOR) manufacturing process was demonstrated in this work. QDa mass detection with electrospray ionization in selected-ion recording mode was utilized for quantitation of GTIs. The method of hydrophilic interaction liquid chromatography coupled with mass spectrometry detection (HILIC-MS) was validated as per International Conference on Harmonization guidelines and was able to quantitate GTIs at 75 p.p.m. with respect to VOR. The HILIC-MS method was achieved using a Primesep B column (150 × 4.6 mm, 5.0 µm; Sielc, USA) using mobile phase consisting of 10 mM ammonium formate buffer pH 3.0 and acetonitrile (5 : 95, v/v) at 0.8 mL/min flow rate. The QDa mass detector was operated in the positive ion mode. Quadrupole mass analyzer was employed in selected-ion monitoring mode using target ion at m/z 142 as [M+H](+).
Epidemie závislosti na nikotinu představuje závažný problém současné medicíny a veřejného zdraví. Nejefektivnějším přístupem k léčbě této závislosti je bezpochyby kombinace farmakoterapie a psychoterapie. Informace o farmakoterapii jsou díky reklamní kampani výrobců široce rozšířené a jsou v povědomí většiny lékařů. O psychoterapii kuřáckého návyku se toho ví jen velmi málo a její efektivní a systematické využití v běžné praxi je spíše výjimkou. Článek popisuje základní konstrukty Transteoretického modelu behaviorálních změn a jejich aplikaci na vybraném vzorku kuřáků. Jeho cílem je představit integrativní psychoterapeutický přístup k léčbě závislosti na nikotinu.
The epidemic of nicotine dependence presents a serious problem for contemporary medicine and public health. The most effective approach to the treatment of nicotine dependence is a combination of pharmacotherapy and psychotherapy. Pharmacotherapy has its own advertising campaign from manufacturers and we have enough information about this approach. However, we have very little information about psychotherapy of nicotine dependence, and its effective and systematic application is rare. The article describes the basic constructs of Transtheoretical model of behavioural changes and its application on a sample of adolescent smokers. The aim of the present study is to introduce an integrated psychotherapy approach to the treatment of nicotine dependence.
- Klíčová slova
- závislost na tabáku, motivace k zanechání kouření, fáze změny, procesy změny, transteoretický model,
- MeSH
- chování mladistvých psychologie MeSH
- financování organizované MeSH
- lidé MeSH
- mladiství MeSH
- poruchy vyvolané užíváním tabáku terapie MeSH
- průzkumy a dotazníky MeSH
- psychoterapie MeSH
- ukončení užívání tabáku metody MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
Despite efforts to develop novel treatment strategies, refractory and relapsing sarcoma, and high-risk neuroblastoma continue to have poor prognoses and limited overall survival. Monocyte-derived dendritic cell (DC)-based anti-cancer immunotherapy represents a promising treatment modality in these neoplasias. A DC-based anti-cancer vaccine was evaluated for safety in an academic phase-I/II clinical trial for children, adolescents, and young adults with progressive, recurrent, or primarily metastatic high-risk tumors, mainly sarcomas and neuroblastomas. The DC vaccine was loaded with self-tumor antigens obtained from patient tumor tissue. DC vaccine quality was assessed in terms of DC yield, viability, immunophenotype, production of IL-12 and IL-10, and stimulation of allogenic donor T-cells and autologous T-cells in allo-MLR and auto-MLR, respectively. Here, we show that the outcome of the manufacture of DC-based vaccine is highly variable in terms of both DC yield and DC immunostimulatory properties. In 30% of cases, manufacturing resulted in a product that failed to meet medicinal product specifications and therefore was not released for administration to a patient. Focusing on the isolation of monocytes and the pharmacotherapy preceding monocyte harvest, we show that isolation of monocytes by elutriation is not superior to adherence on plastic in terms of DC yield, viability, or immunostimulatory capacity. Trial patients having undergone monocyte-interfering pharmacotherapy prior to monocyte harvest was associated with an impaired DC-based immunotherapy product outcome. Certain combinations of anti-cancer treatment resulted in a similar pattern of inadequate DC parameters, namely, a combination of temozolomide with irinotecan was associated with DCs showing poor maturation and decreased immunostimulatory features, and a combination of pazopanib, topotecan, and MTD-based cyclophosphamide was associated with poor monocyte differentiation and decreased DC immunostimulatory parameters. Searching for a surrogate marker predicting an adverse outcome of DC manufacture in the peripheral blood complete blood count prior to monocyte harvest, we observed an association between an increased number of immature granulocytes in peripheral blood and decreased potency of the DC-based product as quantified by allo-MLR. We conclude that the DC-manufacturing yield and the immunostimulatory quality of anti-cancer DC-based vaccines generated from the monocytes of patients were not influenced by the monocyte isolation modality but were detrimentally affected by the specific combination of anti-cancer agents used prior to monocyte harvest.
- Publikační typ
- časopisecké články MeSH
Tobolky ETALOCK splňují požadavky kladené na tvrdé želatinové tobolky. Podíl vadných produktůpři jejich formování a plnění se pohybuje v rozmezí 0,7 až 1,5 %. Pokud plnící stroje vyřazují i tobolkybez zřejmých vad, souvisí to s nedokonalým technickým stavem plniček.
The capsules ETALOCK meet the requirements for hard gelatine capsules. The share of defectiveproducts in the process of their forming and filling ranges within 0.7–1.5 %. If the filling machineseliminate also capsules without evident defects, it is due to the imperfect technical conditions of thefilling machines.
