Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms.
We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.
Arakawa
Yotaro
Y
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Kawakami
Shigeru
S
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000779:Anesthetics, Local / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004304:Dosage Forms; D005079:Excipients; D005456:Fluorescent Dyes; D007660:Ketoprofen / Q000008:administration & dosage; D008012:Lidocaine / Q000008:administration & dosage; D008055:Lipids / Q000737:chemistry; D014014:Tissue Adhesives; D014462:Ultrafiltration; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D005079:Excipients; D005456:Fluorescent Dyes; D008055:Lipids; D014014:Tissue Adhesives; D047392:beta-Cyclodextrins; D007660:Ketoprofen; D008012:Lidocaine