The use of 13C solid state NMR to elucidate physico-chemical association in Eudragit RS100 microencapsulated acyl esters of salicylic acid.
A series of homogeneous Eudragit RS100 matrix microspheres containing molecularly dispersed acylated esterified homologues of salicylic acid, (acetylsalicylic acid, valerylsalicylic acid, or caprylsalicylic acid) were prepared in order to investigate the effect of encapsulation on solid-state orientation of the encapsulated molecule. Electrostatic association of the drug with the charged quaternary residues in the polymer may be responsible for the previously observed stability of acetylsalicylic acid (ASA) in aqueous swollen ASA-loaded Eudragit RS100 microspheres. Evaluation of the 13C nuclear magnetic resonance spectra for evidence of structural association of the incorporated probe molecules indicated that alteration of the microenvironment of the incorporated solutes had occurred. For instance, increasing the aliphatic character of the acyl side chain resulted in an increase in the upfield shift of the acyl bearing aromatic ring carbon, (C2), in the incorporated probe molecule as compared to the unincorporated probe molecule. Similarly, a downfield perturbation in the chemical shift of the free acid bearing aromatic ring carbon, (C1), was also observed. This microenvironment electrostatic shielding in the proximity of the ester carbonyl is attributed to an increase in the association of the probe molecule with the polymer subunits. Thereby, it is postulated that the matrix incorporated probe molecule is essentially shielded from hydrolytic attack until it is liberated into the external aqueous environment.
Vachon
M G
MG
Université de Limoges, France.
Nairn
J G
JG
D000180:Acrylic Resins / Q000737:chemistry*; D002247:Carbon Isotopes; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008863:Microspheres; D011109:Polymethacrylic Acids; D012459:Salicylates / Q000737:chemistry*; D020156:Salicylic Acid; D055672:Static Electricity
D000180:Acrylic Resins; D002247:Carbon Isotopes; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D012459:Salicylates; C038300:methylmethacrylate-methacrylic acid copolymer; D020156:Salicylic Acid