263 research outputs found
Quality assessment of total parenteral nutrition admixtures by the use of fractional factorial design
Background/Aim. Parenteral nutrition as a specific aspect of providing nutritients still remains a permanent topic of both theoretical and experimental research. Total parenteral nutrition (TPN) admixtures have complex contents making difficult to maintain their stability. The most critical parameter is the diameter of a lipid droplet, i.e. droplet size distribution. It is recommended that droplet size should not be more than
Integrisani biofarmaceutski pristup u razvoju i karakterizaciji lekova: opŔti koncept i primena
The importance of biopharmaceutical considerations in pharmaceutical development and drug characterization has been well recognized both by pharmaceutical industry and regulatory authorities as a tool to establish predictive relationships between drug product quality attributes (in vitro data) and its clinical performance (in vivo data). In the present paper, contemporary biopharmaceutics toolkit including in vivo predictive dissolution testing, Biopharmaceutics Classification System, physiologically based pharmacokinetic and biopharmaceutics modeling and simulation, in vitro-in vivo correlation and biowaiver, are reviewed with regards to relevant general principles and applicability. The recently introduced innovative strategy for patient-centric drug development using an integrated systems approach grounded in fundamental biopharmaceutics concepts, clinical insights and therapeutic drug delivery targets, described as Biopharmaceutics Risk Assessment Roadmap (BioRAM) is also presented. Further development in the field will benefit from joint efforts and exchange of knowledge and experiences between pharmaceutical industry and regulatory authorities for the common goal to accelerate development of effective and safe drug products designed in accordance with patientsā needs and expectations.ZnaÄaj biofarmaceutskih razmatranja u razvoju i karakterizaciji lekova s ciljem uspostavljanja korelacije i moguÄnosti predviÄanja odnosa izmeÄu in vitropodataka, odnosno karakteristika kvaliteta leka i njegovog in vivoponaÅ”anja/kliniÄkog uÄinka, prepoznata je kako od strane farmaceutske industrije, tako i od strane odgovarajuÄih regulatornih tela. U radu je dat pregled savremenih biofarmaceutskih alata,ukljuÄujuÄi prediktivno ispitivanje brzine rastvaranja lekovite supstance iz farmaceutskog oblika leka, Biofarmaceutski sistem klasifikacije, fizioloÅ”ki zasnovano farmakokinetiÄko i biofarmaceutsko modelovanje i simulacije, in vitro-in vivokorelaciju i moguÄnost izostavljanja in vivostudija bioekvivalencije (engl. biowaiver) iz aspekta opÅ”tih principa i moguÄnosti primene u razvoju i karakterizaciji lekova.Predstavljena je i nedavno osmiÅ”ljena inovativna strategija za razvoj leka usmerena ka pacijentu, uz primenu integrisanog sistemskog pristupa zasnovanog na osnovnim biofarmaceutskim konceptima, uvidu u kliniÄku situaciju i definisanim terapijskim ciljevima oznaÄena kao Plan aktivnosti za procenu biofarmaceutskog rizika (engl. Biopharmaceutics Risk Assessment Roadmap, BioRAM). OÄekuje se da Äe daljem razvoju u ovoj oblasti najviÅ”e doprineti združene aktivnosti i razmena znanja i iskustava izmeÄu farmaceutskih kompanija i regulatornih agencija sa zajedniÄkim ciljem da se ubrza razvoj efikasnih i bezbednihlekova dizajniranih u skladu sa potrebama i oÄekivanjima pacijenata
ANALIZA BRUTO DOMAÄEG PROIZVODA OD 2000. DO 2007. GODINE PRIMJENOM STATISTIÄKIH METODA
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Izazovi Äetvrte industrijske revolucije: primena digitalnih tehnologija u farmaceutskoj industriji
The fourth industrial revolution brought with it the development and application of
advanced, digital technologies, in all segments of the pharmaceutical industry: from the
discovery of new active substances to post-marketing monitoring of the drug. New, virtual
technologies are: artificial intelligence, quantum computing, blockchain,
telecommunications, Internet of Things, augmented, virtual and mixed reality. Many research
and development centers in the pharmaceutical industry use artificial intelligence
technologies in the discovery of new active substances, in silico modeling of drug release and
absorption, optimization of drug formulation composition and production process and
simulation of clinical trials. Blockchain technology is beginning to be used in drug
distribution and makes it easier to reliably track pharmaceutical products at every step of
the supply chain. In this way, the possibility of distributing counterfeit medicines can be
reduced to a minimum. Virtual reality is used for drug discovery and design, enabling 3D
visualization of drug molecular structures. In R&D laboratories, it is used in the planning of
experiments; it can also be used in pharmaceutical education. In Mixed Reality, elements
from the real and virtual worlds coexist, allowing users to "enter" the combined world of real
and digital and move through it using state-of-the-art tools and sensors. There are a number
of challenges that need to be overcome in order to accelerate the use of new and
revolutionary virtual technologies, but the benefits of applying these technologies and the
opportunities they provide in the advancement of the pharmaceutical industry are
promising.Äetvrta industrijska revolucija je donela sa sobom razvoj i primenu naprednih,
digitalnih tehnologija, u svim segmentima razvoja i rada farmaceutske industrije: od otkriÄa
novih aktivnih supstanci do postmarkentinÅ”kog praÄenja leka. Nove, virtuelne tehnologije su:
veÅ”taÄka inteligencija, kvantno raÄunarstvo, blockchain, telekomunikacije, internet stvari,
proŔirena, virtuelna i meŔovita stvarnost. U mnogim centrima istraživanja i razvoja u
farmaceutskoj industriji se koriste tehnologije veÅ”taÄke inteligencije u otkriÄu novih aktivnih
supstanci, za in silico modelovanje oslobaÄanja i resorpcije leka, optimizaciju sastava
formulacije leka i procesa proizvodnje i simulacije kliniÄkih ispitivanja. Blockchain
tehnologija poÄinje da se koristi u distribuciji lekova i olakÅ”ava pouzdano pracĢenje
farmaceutskih proizvoda na svakom koraku lanca snabdevanja. Na ovaj naÄin se može
smanjiti na minimum moguÄnost distribucije falsifikovanih lekova i obezbediti bezbednost
distributivnog lanca. Virtuelna stvarnost se primenjuje za otkrivanje i dizajn lekova,
omoguÄavajuÄi 3D vizualizaciju molekularnih struktura lekova. U laboratorijama se
primenjuje u planiranju eksperimenata; može se koristiti i u okviru farmaceutskog
obrazovanja, za obuku studenata. U MeŔovitoj stvarnosti, elementi iz stvarnog i virtuelnog
sveta koegzistiraju, omoguÄavajuÄi korisnicima da āuÄuā u kombinovani svet realnog i
digitalnog i da se kreÄu kroz njega koristeÄi najsavremenije alate i senzore. U farmaceutskoj
industriji, Microsoft HoloLens je koriÅ”Äen kao primer meÅ”ovite stvarnosti, koja Äe se koristiti
u razliÄitim oblastima: od sinteze i razvoja lekova, analitiÄkih procedura, proizvodnje,
inspekcije, pa do pakovanja i Äuvanja lekova. Postoji niz izazova koje treba prevaziÄi kako bi
se ubrzala upotreba novih i revolucionarnih virtuelnih tehnologija, ali su prednosti primene
ovih tehnologija i moguÄnosti koje pružaju u napretku farmaceutske industrije velike.VIII Kongres farmaceuta Srbije sa meÄunarodnim uÄeÅ”Äem, 12-15.10.2022. Beogra
Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeÅ”e u formulaciji i karakterizaciji Ävrstih samo-nanoemulgujuÄih terapijskih sist
One of the problems with orally used drugs is their poor solubility, which can be overcome by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). The aim is to choose the appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol (R) (1: 1)) and cosurfactant (Transcutol (R) HP) are formed by applying mixture design. 16 formulations were formulated, where the proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin (R) UFl2, Neusilin (R) FL2, Sylysia (R) 320 and diatomite were used as the carriers. The ratio of SNEDDS: carrier was 1: 1 or 2: 1. Dissolution testing was carried out in the rotation paddles apparatus. Characterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02 +/- 34.09 nm and PdI 0.184 +/- 0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia (R) 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate of carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability
Insight into the formation of glimepiride nanocrystals by wet media milling
Nanocrystal formation for the dissolution enhancement of glimepiride was attempted
by wet media milling. Di erent stabilizers were tested and the obtained nanosuspensions were
solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility
by dynamic light scattering, physicochemical properties by di erential scanning calorimetry (DSC),
FT-IR spectroscopy, powder X-ray di raction (PXRD), and scanning electron microcopy (SEM), as
well as dissolution rate. Lattice energy frameworks combined with topology analysis were used in
order to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with
narrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and PharmacoatĀ® 603
stabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals
during spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic
transformations during processing, and that the milling process induces changes in the hydrogen
bonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed
the existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD
analysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the
important influence of the stabilizer on the dissolution rate of the nanocrystals
Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading
Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers
Powder bed fusionālaser beam (PBF-LB) three-dimensional (3D) printing: Influence of laser hatching distance on the properties of zolpidem tartrate tablets
Laser sintering, known as powder bed fusionālaser beam (PBF-LB), offers promising potential for the fabrication of patient-specific drugs. The aim of this study was to provide an insight into the PBF-LB process with regard to the process parameters, in particular the laser hatching distance, and its influence on the properties of zolpidem tartrate (ZT) tablets. PHARMACOATĀ® 603 was used as the polymer, while CandurinĀ® Gold Sheen and AEROSILĀ® 200 were added to facilitate 3D printing. The particle size distribution of the powder blend showed that the layer height should be set to 100 Āµm, while the laser hatching distance was varied in five different steps (50, 100, 150, 200 and 250 Āµm), keeping the temperature and laser scanning speed constant. Increasing the laser hatching distance and decreasing the laser energy input led to a decrease in the colour intensity, mass, density and hardness of the ZT tablets, while the disintegration and dissolution rate were faster due to the more fragile bonds between the particles. The laser hatching distance also influenced the ZT dosage, indicating the importance of this process parameter in the production of presonalized drugs. The absence of drug-polymer interactions and the amorphization of the ZT were confirmed
Stabilnost lekova - industrijski aspect
Stability testing is carried out in several phases of new product development. The effect of various external factors on possible formulations, compatibility of active pharmaceutical ingredient, excipients and primary packaging material, is examined in early phases of development. Possible pathways of degradation are defined, and degradation rate is estimated by subjecting the products to different, extreme conditions. The results obtained during this phase of testing are used for defining the testing parameters in formal stability studies. Numerous guidelines, which define the testing parameters, are used in this phase of testing. The principal elements which are defined include testing conditions and testing frequency. An accelerated stability testing is carried out over a period of 6 months, whereby a product is exposed to the temperature exceeding the expected warehousing temperature, while a long-term stability testing is performed under the predicting storage conditions, and the length of testing corresponds to the envisaged shelf life. Photostability testing is carried out within a stress testing, and in certain cases, in use stability testing is carried out, whereby storage conditions and the period within which a product must be used after the first opening, i.e. reconstitution, are defined. Testing results are also used for establishing the final specifications of the quality of medicinal products, particularly from the aspect of degradation products (impurities). Various statistical methods and mathematical models, such as artificial neural networks, are used in results processing for the purpose of estimating the stability in a shorter period of time.Ispitivanje stabilnosti realizuje se u viÅ”e faza razvoja novog proizvoda. U ranim fazama razvoja ispituju se uticaji razliÄitih spoljaÅ”njih faktora (temperatura, vlaga, svetlost, kiseonik, mikroorganizmi) na potencijalne formulacije, kompatibilnost lekovite supstance, pomoÄnih supstanci i kontaktne ambalaže. Kondicioniranjem proizvoda u razliÄitim, ekstremnim uslovima, definiÅ”u se moguÄi putevi degradacije i predviÄa brzina degradacije. Rezultati koji se dobiju u toku ove faze ispitivanja koriste se za definisanje parametara ispitivanja u formalnim studijama stabilnosti. U ovoj fazi ispitivanja, primenjuju se brojne smernice kojima se definiÅ”u parametri koji Äe se ispitivati. Osnovni elementi koji se definiÅ”u jesu uslovi ispitivanja i frekvenca ispitivanja. Ubrzano ispitivanje stabilnosti sprovodi se u trajanju od 6 meseci, pri Äemu se proizvod izlaže temperaturi viÅ”oj od oÄekivane temperature skladiÅ”tenja; dugotrajno ispitivanje se izvodi pod oÄekivanim uslovima Äuvanja, a dužina ispitivanja se poklapa sa predviÄenim rokom trajanja. U okviru stres ispitivanja se vrÅ”i i ispitivanje fotostabilnosti, a u pojedinim sluÄajevima, vrÅ”i se ispitivanje in use stabilnosti, pri Äemu se definiÅ”u uslovi Äuvanja i rok u kome se proizvod mora upotrebiti nakon prvog otvaranja, odnosno rekonstitucije. Rezultati ispitivanja koriste se i za postavljanje konaÄnih specifikacija kvaliteta lekova, posebno sa aspekta degradacionih proizvoda (neÄistoÄa). U obradi rezultata koriste se razliÄite statistiÄke metode i matematiÄki modeli, kao Å”to su veÅ”taÄke neuronske mreže, u cilju predviÄanja stabilnosti u kraÄem vremenskom roku
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