Solid dispersions for preparation of phototoxic supersaturated solutions for antimicrobial photodynamic therapy (aPDT) Studies on curcumin and curcuminoides L

• Published in: European journal of pharmaceutics and biopharmaceutics 2013, Vol.83 (1), p.95-105
• Main Authors: BEE HEGGE, Anne, VUKICEVIC, M, BRUZELL, E, KRISTENSEN, S, TØNNESEN, H. H
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; beta-Cyclodextrins - chemistry; Biological and medical sciences; Curcumin - administration & dosage; Curcumin - chemistry; Curcumin - pharmacology; Drug Stability; Drug Storage; Escherichia; Escherichia coli; Escherichia coli - drug effects; Excipients - chemistry; Freeze Drying; General pharmacology; Hypromellose Derivatives; Medical sciences; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Porosity; Solubility; Time Factors
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2012.09.011

Curcumin is under investigation as a potential photosensitizer (PS) in antimicrobial photodynamic therapy (aPDT). The therapeutic potential of curcumin as a PS is limited by its low aqueous solubility, susceptibility to hydrolytic and photolytic degradation, and limited phototoxicity toward Gram negative (G-) bacteria. Supersaturated solutions of curcumin have demonstrated high phototoxicity toward several species of Gram positive (G+) bacteria as well as the G-Escherichia (E) coli. Thus, solid dispersions that can form supersaturated solutions of curcumin upon hydration may be beneficial in aPDT. In the present study, solid dispersions of curcumin have been prepared through lyophilization of concentrated solutions obtained from dissolution of hydroxypropyl-β-cyclodextrin (HPβCD)-curcumin co-precipitates. Hydroxypropyl methylcellulose (HPMC) was added to curcumin solutions prior to lyophilization. The resulting lyophilizates were porous, amorphous and hydrated and dissolved rapidly in contact with a model physiological salt solution. The detected drug load of the lyophilizates was in the range 0.5-1.0% (w/w) and was dependent on the selected ratio between HPβCD and curcumin in the co-precipitate. The lyophilizate with the highest drug load could easily be dissolved in aqueous medium to form curcumin solutions of relevant concentrations for aPDT (i.e., 10μM). Selected solutions of the curcumin solid dispersions showed a pronounced decrease in curcumin concentration up to 90% after storage for 168h, which indicated that supersaturated curcumin solutions were initially formed upon dissolution of the lyophilizates. Both freshly prepared and 2days old solutions of one selected curcumin lyophilizate induced significant inactivation of E. coli (∼1% bacterial survival) after exposure to a light dose of only 5J/cm(2).