The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets

Grund, Julia; Koerber, Martin; Walther, Mathias; Bodmeier, Roland

doi:10.1016/j.ijpharm.2014.04.033

Cited by 48 publications

(18 citation statements)

References 30 publications

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“…Water ingress leads to series of notable events that eventually lead to degradation of the PLGA polymer. Initial incursion of water leads to polymer hydration, after which degradation ensues, and finally solubilization of the polymer [1,[3][4][5]. Hence, measurement of moisture uptake by the polymer during the initial stages of hydration is crucial to the understanding of the biodegradation process.…”

Section: Moisture Uptakementioning

confidence: 99%

“…Depending on the chemical nature of the polymer, the presence of water may result in certain desirable or undesirable changes, causing a profound impact on the behavior of the polymer. Understandably, the manipulation of the rate and extent of moisture in a polymer has been the subject of much research, notably in the field of dosage form design and drug delivery [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Hydration on Physicochemical Properties of End-Capped PLGA

D’Souza

Dorati

DeLuca

2014

Advances in Biomaterials

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The objective of this study was to assess the physicochemical effects of hydrating a hydrophobic end-capped poly(lactide-coglycolide) (PLGA) polymer in the liquid and vapor state. PLGA RG503 polymer was incubated at 37 ∘ C in 0.5% polyvinyl alcohol (PVA) solution and at 90% RH. Samples were withdrawn at predetermined intervals and changes to polymer properties like glass transition temperature (T g ), moisture uptake, molecular weight change, and % acid number were determined using differential scanning calorimetry, Karl Fisher titrimetry, gel permeation chromatography, and acid base titrimetry, respectively. Study results showed that T g was depressed instantaneously upon hydration, indicating that bulk water acted as a plasticizer of hydrophobic end-capped PLGA. T g values decreased to levels below the incubation temperature when hydrated in 0.5% PVA solution but not in 90% RH. The drop in T g exhibited a linear relationship ( 2 > 0.99) to the amount of water uptake by the polymer; higher moisture uptake was noted with liquid water. Removal of moisture from the polymer matrix resulted in recovery of T g , only up to a period of 14 days. Presence of water in liquid or vapor form caused a reduction in molecular weight of the polymer and a corresponding increase in % acid number over the duration of the study.

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Section: Moisture Uptakementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Hydration on Physicochemical Properties of End-Capped PLGA

D’Souza

Dorati

DeLuca

2014

Advances in Biomaterials

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“…Lactose, the water-soluble filler, quickly dissolves in the media, leaving the water-filled pores that easily allow Pal release by diffusion. The diffusion coefficient was reported to rise with higher initial porosity, which explains the result obtained for the dissolution profiles 13,23…”

Section: Resultsmentioning

confidence: 58%

“…As expected, the higher the crushing strength, the slower the release, but it seems that if an average value of 350 N is attained, the influence of the crushing strength weakens, up to a limit where the dissolution profile is no longer affected (Figure 2B). In insoluble matrix-type tablets, drug release increases with the increase in initial porosity 23. Lactose, the water-soluble filler, quickly dissolves in the media, leaving the water-filled pores that easily allow Pal release by diffusion.…”

Section: Resultsmentioning

confidence: 99%

Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone

Iurian

Turdean

Tomuță

2017

DDDT

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This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio (X1), the type of hydrophilic polymer (X2), and the percentage of hydrophilic polymer (X3) on the percentages of dissolved Pal over 24 h (Y1–Y9). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring.

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“…U tom slučaju mehanička svojstva gela ključan su parametar koji kontrolira oslobađanje lijeka, a znatno ovisi o svojstvima polimera kao što je njegov kemijski sastav, molekulska masa te međumolekulske interakcije s otapalom, djelatnom tvari i ostalim pomoćnim tvarima u formulaciji. 37,38 Kod polimera koji ne upijaju vodu i ne bubre dolazi do močenja površine polimernog matriksa koja postupno erodira i ne stvara se gelirani sloj. Na taj način čestice lijeka postupno izlaze iz matriksa isključivo zbog površinske erozije.…”

Section: 2unclassified

Primjena polimera u farmaceutskoj industriji

Jerbić

2017

Kem. Ind.

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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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The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets

Cited by 48 publications

References 30 publications

Effect of Hydration on Physicochemical Properties of End-Capped PLGA

Effect of Hydration on Physicochemical Properties of End-Capped PLGA

Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone

Primjena polimera u farmaceutskoj industriji

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