Influence of pH Modulation on Dynamic Behavior of Gel Layer and Release of Weakly Basic Drug from HPMC/Wax Matrices, Controlled by Acidic Modifiers Evaluated by Multivariate Data Analysis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F17%3A43875882" target="_blank" >RIV/62157124:16370/17:43875882 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1208/s12249-016-0588-x" target="_blank" >http://dx.doi.org/10.1208/s12249-016-0588-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1208/s12249-016-0588-x" target="_blank" >10.1208/s12249-016-0588-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Influence of pH Modulation on Dynamic Behavior of Gel Layer and Release of Weakly Basic Drug from HPMC/Wax Matrices, Controlled by Acidic Modifiers Evaluated by Multivariate Data Analysis

Popis výsledku v původním jazyce

The solubility of weakly basic drugs in passage through gastrointestinal tract leads to their pH-dependent release from extended release formulations and to lower drug absorption and bioavailability. The aim of this study was to modulate the micro-environmental pH of hypromellose/montanglycol wax matrices and to observe its influence on the release of weakly basic drug verapamil hydrochloride (VH) with a pH-dependent solubility with respect to gel layer formation and its dynamics. For this study, malic and succinic acids differing in their solubility and pKa were selected as pH modifiers. The dissolution studies were performed by the method of changing pH. Within the same conditions, pH, thickness, and penetration force of the gel layer were measured as well. From the PCA sub-model, it is evident that a higher acid concentration ensured lower gel pH and conditions for higher drug solubility, thus creating larger gel layer with smaller rigidity, resulting in higher VH release during the dissolution test. Incorporation of stronger and more soluble malic acid (100 mg/tablet) created the most acidic and the thickest gel layer through which a total of 74% of VH was released. Despite having lower strength and solubility, matrices containing succinic acid (100 mg/tablet) released a comparable 71% of VH in a manner close to zero-order kinetics. The thinner and less rigid gel layers of the succinic acid matrices allowed an even slightly faster VH release at pH 6.8 than from matrices containing malic acid. Thus acid solubility is more parametrically significant than acid pKa for drug release at pH 6.8.

Název v anglickém jazyce

Influence of pH Modulation on Dynamic Behavior of Gel Layer and Release of Weakly Basic Drug from HPMC/Wax Matrices, Controlled by Acidic Modifiers Evaluated by Multivariate Data Analysis

Popis výsledku anglicky

The solubility of weakly basic drugs in passage through gastrointestinal tract leads to their pH-dependent release from extended release formulations and to lower drug absorption and bioavailability. The aim of this study was to modulate the micro-environmental pH of hypromellose/montanglycol wax matrices and to observe its influence on the release of weakly basic drug verapamil hydrochloride (VH) with a pH-dependent solubility with respect to gel layer formation and its dynamics. For this study, malic and succinic acids differing in their solubility and pKa were selected as pH modifiers. The dissolution studies were performed by the method of changing pH. Within the same conditions, pH, thickness, and penetration force of the gel layer were measured as well. From the PCA sub-model, it is evident that a higher acid concentration ensured lower gel pH and conditions for higher drug solubility, thus creating larger gel layer with smaller rigidity, resulting in higher VH release during the dissolution test. Incorporation of stronger and more soluble malic acid (100 mg/tablet) created the most acidic and the thickest gel layer through which a total of 74% of VH was released. Despite having lower strength and solubility, matrices containing succinic acid (100 mg/tablet) released a comparable 71% of VH in a manner close to zero-order kinetics. The thinner and less rigid gel layers of the succinic acid matrices allowed an even slightly faster VH release at pH 6.8 than from matrices containing malic acid. Thus acid solubility is more parametrically significant than acid pKa for drug release at pH 6.8.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

AAPS PharmSciTech

ISSN

1530-9932

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1242-1253

Kód UT WoS článku

000404548700026

EID výsledku v databázi Scopus

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