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•Novel high throughput electrospinning method is introduced in detail.•Low boiling point solvents can be used as there is no high free liquid surface.•FEA proved charge concentration ...is occurred that helps in Taylor-cone formation.•Nanofiber morphology is similar to that of the fibers of single needle method.
A novel spinneret and modified electrospinning method is introduced wherewith nanofibers can be produced with high-throughput. The main conception of the system is to continuously supply the polymeric solution through a narrow, but long gutter bounded by a metal electrode having sharp edge. As there is no high free liquid surface volatile and low boiling point solvents can be applied that makes the method suitable for pharmaceutical and biomedical applications. In this study the operation of the spinneret was tested with polyacrylnitrile/dimethyl-formamide and poly-vinylpirrolidone/ethanol solutions. The charge concentration – related from the construction – was investigated by finite element analysis. The highest electrical charge density is formed along the sharp edge what results many self-assembled Taylor-cones that is also confirmed by the first operation experiences. The productivity of the technique can be two orders of magnitude higher than that of the single capillary method.
Recently, electrospinning (ES) of fibers has been shown to be an attractive strategy for drug delivery. One of the main features of ES is that a wide variety of drugs can be loaded into the fibers to ...improve their bioavailability, to enhance dissolution, or to achieve controlled release. Besides, ES is a continuous technology with low energy consumption, which can make it a very economic production alternative to the widely used freeze drying and spray drying. However, the low production rate of laboratory‐scaled ES has limited the industrial application of the technology so far. This article covers the various ES technologies developed for scaled‐up fiber production with an emphasis on pharmaceutically relevant examples. The methods used for increasing the productivity are complied, which is followed by a review of specific examples from literature where these technologies are utilized to produce oral drug delivery systems. The different technologies are compared in terms of their basic principles, advantages, and limitations. Finally, the different downstream processing options to prepare tablets or capsules containing the electrospun drug are covered as well.
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Application of scaled‐up electrospinning in oral drug delivery.
In chronic intestinal diseases like inflammatory bowel disease, parenteral administration of biopharmaceuticals is associated with numerous disadvantages including immune reactions, infections, low ...patient compliance, and toxicity caused by high systemic bioavailability. One alternative that can potentially overcome these limitations is oral administration of biopharmaceuticals, where the local delivery will reduce the systemic exposure and furthermore the manufacturing costs will be lower. However, the development of oral dosage forms that deliver the biologically active form to the intestines is one of the greatest challenges for pharmaceutical technologists due to the sensitive nature of biopharmaceuticals.
The present article discusses the various drug delivery technologies used to produce orally administered solid dosage forms of biopharmaceuticals with an emphasis on colon-targeted delivery. Solid oral dosage compositions containing different types of colon-targeting biopharmaceuticals are compiled followed by a review of currently applied and emerging drying technologies for biopharmaceuticals. The different drying technologies are compared in terms of their advantages, limitations, costs and their effect on product stability.
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•Fully continuous melt granulation-based powder-to-tablet line was developed.•The flowability and tabletability were improved significantly.•Caffeine-loaded tablets with increased ...breaking force (from 15 N to over 80 N) were produced.•The tablets had excellent friability and immediate release dissolution.•Scale-up production (from 0.5 kg/h to 8 kg/h) was accomplished with the same system.
In the last decades, continuous manufacturing (CM) has become a research priority in the pharmaceutical industry. However, significantly fewer scientific researches address the investigation of integrated, continuous systems, a field that needs further exploration to facilitate the implementation of CM lines. This research outlines the development and optimization of an integrated, polyethylene glycol aided melt granulation-based powder-to-tablet line that operates fully continuously. The flowability and tabletability of a caffeine-containing powder mixture were improved through twin-screw melt granulation resulting in the production of tablets with improved breaking force (from 15 N to over 80 N), excellent friability, and immediate release dissolution. The system was also conveniently scaleable: the production speed could be increased from 0.5 kg/h to 8 kg/h with only minimal changes in the process parameters and using the same equipment. Thereby the frequent challenges of scale-up can be avoided, such as the need for new equipment and separate optimization.
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High speed electrospinning (HSES), compatible with pharmaceutical industry, was used to demonstrate the viability of the preparation of drug-loaded polymer nanofibers with radically ...higher productivity than the known single-needle electrospinning (SNES) setup. Poorly water-soluble itraconazole (ITRA) was formulated with PVPVA64 matrix polymer using four different solvent-based methods such as HSES, SNES, spray drying (SD) and film casting (FC). The formulations were assessed in terms of improvement in the dissolution rate of ITRA (using a “tapped basket” dissolution configuration) and analysed by SEM, DSC and XRPD. Despite the significantly increased productivity of HSES, the obtained morphology was very similar to the SNES nanofibrous material. ITRA transformed into an amorphous form, according to the DSC and XRPD results, in most cases except the FC samples. The limited dissolution of crystalline ITRA could be highly improved: fast dissolution occurred (>90% within 10min) in the cases of both (the scaled-up and the single-needle) types of electrospun fibers, while the improvement in the dissolution rate of the spray-dried microspheres was significantly lower. Production of amorphous solid dispersions (ASDs) with the HSES system proved to be flexibly scalable and easy to integrate into a continuous pharmaceutical manufacturing line, which opens new routes for the development of industrially relevant nanopharmaceuticals.
The aims of this study were to evaluate electrospinning as a continuous alternative to freeze drying in the production of a reconstitution injection dosage form, and to prove that aqueous ...electrospinning can be realized with a high production rate at room temperature. High-speed electrospinning with a novel continuous cyclone collection was used to manufacture a formulation of the poorly water-soluble antifungal voriconazole (VOR) with sulfobutylether-β-cyclodextrin (SBE-β-CD). The freeze-dried, marketed product of this drug substance, Vfend® also contains SBE-β-CD as excipient. SBE-β-CD acted as a ‘quasi-polymer’, and it could be electrospun despite its low molecular mass (2163 Da). According to X-ray diffraction and differential scanning calorimetry, no traces of crystalline VOR were detectable in the fibers. Furthermore, Raman mapping and energy dispersive spectroscopy measurements showed a uniform distribution of amorphous VOR in the fibers. Reconstitution tests carried out with ground fibrous powder showed complete dissolution resulting in a clear solution after 30 s (similarly to Vfend®). The high productivity rate (~240 g/h) achieved using high-speed electrospinning makes this scaled-up, continuous and flexible manufacturing process capable of fulfilling the technological and capacity requirements of the pharmaceutical industry. This work shows that aqueous high-speed electrospinning, being a continuous and high-throughput process, is an economically viable production alternative to freeze drying.
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•Continuous collection of drug-loaded fibers by a cyclone attached to the high-speed electrospinning machine is performed•Viscous aqueous solution of sulfobutylether-β-cyclodextrin can be electrospun with high production rate at room temperature•Voriconazole becomes molecularly dispersed in the cyclodextrin matrix during electrospinning, the product dissolves in 30 s•Scaled-up electrospinning of aqueous solutions at room temperature can be a viable, continuous alternative to freeze drying
In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different ...formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%. Changing the salt forming agent as well resulted in approximately 20% of flux reduction compared to the brand formulation. This significant difference was clearly shown in the published in vivo results as well. The use of additional lactose monohydrate in the formulation also leads to approximately 10% reduction in flux. The results show that by changing excipients, the dissolution of telmisartan was not altered significantly, but the flux through the membrane was found to be significantly changed.
These results pointed out the limitations of traditional USP dissolution tests and emphasized the importance of simultaneously measuring dissolution and absorption, which allows the complex effect of formulation excipients on both processes to be measured. Moreover, the in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo bioequivalence study results.
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Raman spectroscopy as a process analytical technology tool was implemented for the monitoring and control of ethanol fermentation carried out with Saccharomyces cerevisiae. The need for the ...optimization of bioprocesses such as ethanol production, to increase product yield, enhanced the development of control strategies. The control system developed by the authors utilized noninvasive Raman measurements to avoid possible sterilization problems. Real‐time data analysis was applied using partial least squares regression (PLS) method. With the aid of spectral pretreatment and multivariate data analysis, the monitoring of glucose and ethanol concentration was successful during yeast fermentation with the prediction error of 4.42 g/L for glucose and 2.40 g/L for ethanol. By Raman spectroscopy‐based feedback control, the glucose concentration was maintained at 100 g/L by the automatic feeding of concentrated glucose solution. The control of glucose concentration during fed‐batch fermentation resulted in increased ethanol production. Ethanol yield of 86% was achieved compared to the batch fermentation when 75% yield was obtained. The results show that the use of Raman spectroscopy for the monitoring and control of yeast fermentation is a promising way to enhance process understanding and achieve consistently high production yield.
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