Microsoft powerpoint - solubility and loading of fluconazole in cross-linked polymers.ppt
Solubility and Loading of Fluconazole in
Maher Khattab, Robert Cochrane, Denis Carr, Mark Livingstone, Janet A Halliday
Controlled Therapeutics (Scotland) Ltd, 1 Redwood Place, Peel Park Campus, East Kilbride G74 5PB, Scotland, UK[email protected]
. Fluconazole solubility
. Target HPBCD and fluconazole
in water at room temperature
content and actual fluconazole content after 3.5
Fluconazole (FU) solubility increased from 5 mg/ml in water
hour dissolution in water at 37
to 100 mg/ml using 2-hydroxy propyl β-cyclodextrin (HPBCD)
(100 mg) or sulfobutyl ether-β-cyclodextrin (SBECD) (50 mg) in
Drug loaded into cross-linked polymers increased as ethanol
percentage in the loading solution increased.
. Solubility of fluconazole with HPBCD or SBECD in 50% ethanol.
Many potential drugs are water insoluble or sparingly soluble
Concentration is mg/1 g of 50% ethanol. (ND: Not determined)
in water, thus limiting their use in various drug formulations, such as hydrogel polymeric systems, aqueous gel formulations, drop
Solubility after overnight
Solubility after overnight
incubation, using HPBCD, at
incubation, using SBECD, at
Loading hydrophobic drugs into hydrogels is problematic,
because water is the main loading medium. Even if hydrophobic
drugs are loaded into hydrogels, they are not easily released.
The poster investigates the solubility of fluconazole in solvents
with and without HPBCD or SBECD. Loading and release of
fluconazole in cross-linked polymers was also studied using different loading media .
3. EXPERIMENTAL METHODS
Solubility of fluconazole was determined by adding drug to
water or water, ethanol and cyclodextrins. Solubility was assessed visually at room temperature. Soluble samples were
incubated at 4°C, 25°C and 37°C overnight and their solubility was re-examined.
Water-swellable crosslinked polyurethane pessaries
. Release of
(polyethylene glycol 8000: dicyclohexylmethane-4, 4-
diisocyanate: hexanetriol, 1:2.8:1.2) of 0.8x10x30 mm were
manufactured  and purified according to in-house procedures.
water at 37
50 mg of fluconazole and 50 mg of HPBCD were loaded into
pessaries overnight by means of solution diffusion and dried
loaded with 50
under vacuum overnight. Loading temperature was 25ºC.
mg of HPBCD
Loading solution varied between water, 25% ethanol and 50%
ethanol. Fluconazole release from the hydrogels was studied by
dissolution (USP paddle method), using the following parameters:
paddle speed 50rpm, temperature 37ºC, media 500ml deionised
degassed water, 20mm path length cells and 261nm.
4. RESULTS AND DISCUSSION
release of 50 mg
5 mg of fluconazole is soluble in 1 g of water; higher amounts
of fluconazole in
water at 37
Table 2 shows the solubility of 50 mg of fluconazole in 1 g of
50% ethanol/water (w/w), containing 0 to 100 mg of HPBCD or
SBECD. As HPBCD content increased, solubility at 4°C also
loaded 50 mg of
increased. Incubating overnight at 25°C and 37°C resulted in
Solubility of FU at 4°C improved using SBECD as compared
Three factors aided the solubility of fluconazole: ethanol, cyclodextrin derivatives
100 mg of fluconazole was also soluble in a solution of 1g of
(HPBCD and SBECD) and temperature, where SBECD is superior to HPBCD.
50% ethanol, containing 100 mg of HPBCD, at 25°C and 37°C.
Fluconazole solubility in the loading solution is a major factor in controll
Loading was assessed by the amount of drug released using
nto cross-linked polymers. As the amount of ethanol in
dissolution testing. As the amount of ethanol in the loading
reases, loaded fluconazole also increases.
solution increases, fluconazole solubility increases and loaded drug increases (Fig. 1 and Table 3). Fig. 2 is the normalised % release, which shows less burst release with 50% ethanol loading
solution. Table 3 shows actual fluconazole potency after 3.5 hour
Controlled Therapeutics is a wholly owned subsidiary of CytokinePharmaSciences inc.
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