Effect of hydrophobicity of a drug on its release from hydrogels with different topological structures

Abstract

The effect of the topological structure; that is, the network heterogeneity, of hydrophobically modified, slightly acidic hydrogels on the binding and release of low molar mass drugs has been studied using ibuprofen and ephedrine as model compounds with varying water solubility. The difference in the heterogeneity of the gels has been produced by the choice of the hydrophobe copolymerized into the polymer network. The effect of the drug loading on the release kinetics has been investigated as well. The release of hydrophobic ibuprofen was slower from a strongly aggregated heterogeneous gel than from a more homogeneous one, because of the strong hydrophobic interaction between ibuprofen and the heterogeneous hydrogel. The release of hydrophilic ephedrine from the homogeneous gel with an initial drug content of 30 wt % of dry polymer showed negative time dependence, indicating that during and after the swelling of the gel, ephedrine started to bind to the polymer. However, the release of ephedrine from a heterogeneous hydrogel increased with time. This shows that the heterogeneous, aggregated polymer binds the hydrophobic substance more strongly than the homogeneous one does, and that the homogeneous network has higher affinity for the basic hydrophilic substance than the heterogeneous one does. The loading contents of ibuprofen and ephedrine affect the release rates in different ways because of the different binding and release mechanisms. The number of binding sites accessible for ephedrine inside the polymer network is assumed to change upon the swelling of the gel.

Investigation of loading and release in PVA‐based hydrogels

“…Here, the most likely explanation seems to be that at high loading the drug formed insoluble clusters in the polymer, which prevented the complete release of the model drugs. 1 This work allowed us to obtain information on the loading and release of low-molecular-weight compounds with positive or negative charges. The charge was the most important factor that influenced the both loading and release processes.…”

“…In this study, we investigated how these variables affected the loading and release of a cationic model compound [Methylene Blue (MB)] and an anionic model compound [Methyl Orange (MO)] from PVA crosslinked with EDTAD. Previous works 1,2,7 have shown that for low-molecular-weight clinical compounds, the most significant factors that influence the release are the polarity and the presence or absence of charges. Therefore, MB and MO should have predictably shown a similar behavior to these pharmaceutical drugs.…”

Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug delivery

“…In the case of these hydrophobic drugs, which were bound to hydrophobic gels by non-polar interactions, the level of gel hydrophobicity was used to control the release. Hence a reduced level of hydration gave rise to slow release of the drug (Lowe et al 1999). In-vivo studies were conducted in the rabbit model to evaluate the absorption of drug from tablets prepared using GCP12,denbufylline,and GDC (20:12:5) with Carbopol 974NF, denbufylline, and GDC (20:12:5)(60:36:4) tablets used as controls.…”

Host–guest interactions in poly(N-isopropylacrylamide) gel

“…various polymers revealed that the more hydrophobic the gel matrix is the stronger is the interaction between ibuprofen and the gel. [12][13][14][15][16] Ibuprofen interacts with PNIPA via hydrogen bonding when its carboxylic group binds either to the carbonyl oxygen or to the nitrogen atoms of the polymer chain in aqueous solution [15]. Dopamine (4-(2-aminoethyl)benzene-1,2-diol) is a neurotransmitter present in the brain and the nervous system.…”