Polymeric dispersive viscosity index improvers of lubricating mineral oils based on styrene, dodecyl-methacrylate, octadecyl methacrylate, and N,N-dimethylaminoethyl methacrylate (d-PSAMA) were produced by performing copolymerizations isothermally up to the high conversion in mineral base oil solution, using monofunctional or bifunctional peroxide initiator. The obtained kinetics results reveal the benefits of the usage of a bifunctional peroxide initiator over a monofunctional, because complete conversion of monomers was accomplished in the shorter reaction time, performing the process in a full batchwise mode. When the bifunctional initiator was applied, the required polymerization temperature was slightly higher (105 °C), and copolymers of higher average molecular weight values (M w = 60−120 kg mol −1 ) were obtained, while in case of the monofunctional peroxide initiator, the reaction temperature was 100 °C, and average molecular weight values of copolymers were M w = 30−100 kg/mol. Investigated application properties demonstrated that d-PSAMA additives were fully comparable with conventional pure methacrylate additives, and also it provided other advantages such as higher viscosity index and kinematic viscosity, lower values of pour point temperatures, as well as better dispersant and detergent properties. Thus, by increasing the N,N-dimethylaminoethyl methacrylate share in copolymers from 2 to 10 mol %, their weight average molecular weight decreased from 120 to 60 kg mol −1 , while kinematic viscosity values at 100 °C remain high and amounted to 14.5 ± 0.5 mm 2 s −1 .
Natural and synthetic polymers have been used in pharmaceutical industry for many years and have important role in the development of the conventional dosage forms or for manufacturing of various drug packaging materials. In recent years, their important application resides in the development of the most sophisticated drug delivery systems where polymers are used as a drug carrier. Biodegradable polymers are particularly attractive for application in drug delivery systems since, once introduced into the human body, they do not require removal or additional manipulation. Their degradation products are normal metabolites of the body or products that can be metabolized and easily cleared from the body. Among that, synthetic polymers offer a wide variety of compositions with adjustable properties. These materials open the possibility of developing new drug delivery systems with specific properties (chemical, interfacial, mechanical and biological) for a given application, simply by changing the building blocks or the preparation technique. Such designed complex drug delivery systems where polymers are used as functional excipients have numerous advantages such as localized delivery of drug, sustained delivery of drug, stabilization of the drug, prevention of drug's adverse side-effects, reduction of dosing frequency, minimization of drug concentration fluctuations in plasma level, improved drug utilization and patient compliance. There are range of differently designed drug delivery systems and their description and mechanism of action will be presented in this paper together with the prominent role of the polymers for each particular system. Additionally, most commonly used synthetic biodegradable polymers in drug delivery systems will be presented together with their degradation mechanism.
SažetakPolimeri i polimerni materijali već su dugi niz godina prisutni u farmaceutskoj industriji, gdje se primjenjuju kao pomoćne tvari za oblikovanje konvencionalnih lijekova ili za izradu ambalaže za lijekove. Međutim sve je veća primjena polimera u naprednim terapijskim sustavima, gdje je oslobađanje djelatne tvari kroz dulje razdoblje kontrolirano najvećim dijelom brzinom degradacije polimera. Poželjno je da polimeri koji se unose u tijelo čo-vjeka budu biorazgradljivi, a to znači da s vremenom potpuno degradiraju na netoksične produkte koji se mogu prirodnim putem izlučiti iz organizma. Također, moraju biti i biokompatibilni, pri čemu u dodiru s organizmom ne izazivaju neželjene nuspojave iako se u tkivu mogu zadržati dulje vrijeme. Tako dizajnirani kompleksni terapijski sustavi u kojima su polimeri funkcionalne djelatne tvari imaju brojne prednosti kao što je jednostavnost i lokaliziranost primjene, produljeno i kontrolirano vrijeme djelovanja lijeka, što znatno smanjuje učestalost primjene. Na taj način smanjena je mogućnost javljanja neželjenih nuspojava, s ciljem poboljšanja kvalitete života pacijenata. Postoje različito dizajnirani sustavi za dostavu lijeka, a njihov pregled te mehanizam djelovanja bit će opisani u sklopu ovog rada zajedno s istaknutom ulogom polimera za svaki pojedini sustav. Ključne riječiPolimeri, farmaceutski oblici, kontrolirano oslobađanje, hidrogelovi UvodFarmaceutski proizvodi mogu se podijeliti prema načinu oslobađanja djelatne tvari na farmaceutske oblike s trenutnim oslobađanjem i farmaceutske oblike s kontroliranim/ produljenim oslobađanjem djelatne tvari. Tradicionalni pristup liječenja bolesti podrazumijeva uzimanje klasičnih farmaceutskih oblika oralnim putem kao što su tablete i kapsule na dnevnoj razini. Kod takvih sustava lijek se oslobađa u probavnom sustav u vrlo kratkom i definiranom vremenu te brzo apsorbira i dospijeva u sistemsku cirkulaciju pacijenta. 1,2 Koncentracija djelatne tvari u plazmi kroz određeno vrijeme iz klasičnog farmaceutskog oralnog oblika s trenutnim oslobađanjem nakon dvostruke primjene prikazan je na slici 1. Na slici se mogu primijetiti tri područja. Prvo područje odnosi se na podterapijsku razinu lijeka u krvi pacijenta koja nije dovoljna za bilo kakav terapijski učinak. Zatim slijedi terapijsko područje, gdje je razina lijeka optimalna i zadnje područje u kojem koncentracija lijeka prelazi najvišu sigurnu razinu lijeka u plazmi.3 Iako se klasični farmaceutski oblici s trenutnim oslobađanjem mogu upotrebljavati prilikom liječenja akutnih i kroničnih bolesti, postoji nekoliko ograničenja kao što je potreba za čestim i višestrukim doziranjem te mogućnost razvoja nuspojava s obzirom na to da koncentracija lijeka može prelaziti najvišu sigurnu razinu u krvi. Navedeni nedostatci mogu se prevladati primjenom farmaceutskih oblika s kontroliranim/produljenim oslobađanjem, odnosno farmaceutskih pripravaka gdje je oslobađanje lijeka i njegova apsorpcija te dospijeće u sistemsku cirkulaciju regulirana samim farmaceutskim oblikom. Farmaceutske formula...
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