Physical stability of amorphous acetanilide derivatives improved by polymer excipients.
Crystallization rates of drug-polymer solid dispersions prepared with acetaminophen (ACA) and p-aminoacetanilide (AAA) as model drugs, and polyvinylpyrrolidone and polyacrylic acid (PAA) as model polymers were measured in order to further examine the significance of drug-polymer interactions. The crystallization of AAA and ACA was inhibited by mixing those polymers. The most effective inhibition was observed with solid dispersions of AAA and PAA. The combination of AAA and PAA showed a markedly longer enthalpy relaxation time relative to drug alone as well as a higher T(g) than predicted by the Gordon-Taylor equation, indicating the existence of a strong interaction between the two components. These observations suggest that crystallization is effectively inhibited by combinations of drug and polymer that show a strong intermolecular interaction due to proton transfer between acidic and basic functional groups.
Miyazaki
Tamaki
T
Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. miyazaki@nihs.go.jp
Yoshioka
Sumie
S
Aso
Yukio
Y
D000083:Acetanilides / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D003890:Desiccation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D013816:Thermodynamics
D000083:Acetanilides; D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers