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Statements

Subject Item
n2:RIV%2F62157124%3A16370%2F13%3A43872198%21RIV14-MSM-16370___
rdf:type
skos:Concept n16:Vysledek
dcterms:description
The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic-lipophilic (hypromellose-montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2h at pH1.2 and then 10h at pH6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals-360 and 480min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p{0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480min. The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic-lipophilic (hypromellose-montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2h at pH1.2 and then 10h at pH6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals-360 and 480min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p{0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480min.
dcterms:title
The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic-Lipophilic Matrices The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic-Lipophilic Matrices
skos:prefLabel
The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic-Lipophilic Matrices The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic-Lipophilic Matrices
skos:notation
RIV/62157124:16370/13:43872198!RIV14-MSM-16370___
n16:predkladatel
n17:orjk%3A16370
n3:aktivita
n11:S
n3:aktivity
S
n3:cisloPeriodika
4
n3:dodaniDat
n10:2014
n3:domaciTvurceVysledku
n4:1212001 n4:8257566 n4:1962213 n4:1449052 n4:5599830 n4:7255985
n3:druhVysledku
n12:J
n3:duvernostUdaju
n18:S
n3:entitaPredkladatele
n7:predkladatel
n3:idSjednocenehoVysledku
71337
n3:idVysledku
RIV/62157124:16370/13:43872198
n3:jazykVysledku
n15:eng
n3:klicovaSlova
gel layer; pH-independent drug release; statistical evaluation; pH-modifiers; matrix tablets
n3:klicoveSlovo
n9:matrix%20tablets n9:statistical%20evaluation n9:gel%20layer n9:pH-independent%20drug%20release n9:pH-modifiers
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[F5DCA30E8E57]
n3:nazevZdroje
AAPS PharmSciTech
n3:obor
n14:FR
n3:pocetDomacichTvurcuVysledku
6
n3:pocetTvurcuVysledku
6
n3:rokUplatneniVysledku
n10:2013
n3:svazekPeriodika
14
n3:tvurceVysledku
Dvořáčková, Kateřina Kejdušová, Martina Vetchý, David Mašková, Eliška Muselík, Jan Doležel, Petr
n3:wos
000330232300008
s:issn
1530-9932
s:numberOfPages
8
n19:doi
10.1208/s12249-013-0019-1
n8:organizacniJednotka
16370