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Enhancement of the rate of solution of relatively insoluble drugs from solid-solid systems prepared by supercritical fluid technology

Ramirez, Carmen Hernandez
http://rave.ohiolink.edu/etdc/view?acc_num=osu1179928429

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Pharmacy.
Supercritical fluid technology, specifically the method of rapid expansion of supercritical solutions (RESS), has been used to prepare small particles consisting of solid solutions of a relatively insoluble drug and a water-soluble excipient. With an increasing number of relatively insoluble compounds being discovered, a general process for enhancing drug dissolution rates would assist formulation of these compounds for therapeutic use. Solid solutions could serve as a means for enhancing drug dissolution rates, since the drug is dispersed in a solid solvent in its smallest form, i.e., a molecule, prior to entering into solution. Therefore, solid solutions consisting of the relatively insoluble model drugs lidocaine or probucol and a water-soluble surfactant, poloxamers 407, 188, or 403 were prepared by RESS processing. Dissolution studies of these systems were performed and evaluated for their ability to enhance drug release rates. Furthermore, the mechanism by which solid solutions form in these systems was determined using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM) was also used to study the surface characteristics of these particulate systems. Dissolution studies of these particles showed an enhanced rate of release of drug in the presence of poloxamer. This enhancement was due to the apparent formation of solid solutions. DSC of these particulate systems also indicated the formation of solid solutions of drug and poloxamer with increasing proportion of poloxamer. With the formation of solid solutions, hydrogen bonding occurred between the drug and poloxamer. This bonding was dependent on the polyoxyethylene chain length of the three poloxamers, i.e., where hydrogen bonding primarily occurs. Solid solutions formed for systems consisting of drug and poloxamers 407 or 188, which have similar polyoxyethylene lengths and hence similar amounts of available sites for bonding. Solid solutions however did not form for systems consisting of drug and poloxamer 403 since poloxamer 403 has approximately half the polyoxyethylene length of poloxamers 407 and 188. Lastly, SEM shows the formation of small particles that vary in appearance as functions of poloxamer concentration.
Sylvan Frank (Advisor)
239 p.
Drug delivery; supercritical fluids; solid dispersions; solid solutions

Recommended Citations

Citations

  • Ramirez, C. H. (2007). Enhancement of the rate of solution of relatively insoluble drugs from solid-solid systems prepared by supercritical fluid technology [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1179928429

    APA Style (7th edition)

  • Ramirez, Carmen. Enhancement of the rate of solution of relatively insoluble drugs from solid-solid systems prepared by supercritical fluid technology. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1179928429.

    MLA Style (8th edition)

  • Ramirez, Carmen. "Enhancement of the rate of solution of relatively insoluble drugs from solid-solid systems prepared by supercritical fluid technology." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1179928429

    Chicago Manual of Style (17th edition)

osu1179928429
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This open access ETD is published by The Ohio State University and OhioLINK.