Dear all,
I use the kneading method in order to encapsulate silicon phthalocyanine dichloride in cyclodextrins (β-CD, γ-CD, HP-β-CD and Me-β-CD). My last calculations gave me encapsulation efficiency greater than 100%. Something went wrong... The protocol I follow is: Add i.e 5 mg of the dry complex of the cyclodextrin to 5 mL of DMF. The system is left under stirring for at least 24 hours. The solution is then filtered and fluorescence is measured.
Has anybody ever had a problem like this before and how did you overcome? How can I separate cyclodextrin complexes from the not encapsulated drug? I tried centrifugation without result.
Thank you!!
Hi Eleni,
0. The complexation itself can enhance the fluorescence (see, e.g., doi:10.1016/j.jpba.2014.02.022, 10.1080/02652030701564555 )
1. It is a common mistake to assume that all the guest molecules form complexes upon kneading the components in a 1:1 molar ratio. More specifically, it is rare that equal molar ratio treatment results in complete complexation. That means the removal of uncomplexed guests is crucial. For the removal, one needs to use a solvent that is not a good guest for CD, does not dissolve the complex or the CD, and does not decompose the guest.
The silicon phthalocyanine dichloride content is an approximate value (~85%, according to, e.g., a known fine chemical supplier), you have to check the CofA for the measured value because the label contains the specification and not the measured value.
If some hydrolysis occurred before the complexation experiments, the content could be higher than expected. 2xOH~1Cl => ~5% more phthalocyanine content.
Because it is a reactive substance, it is difficult to find a suitable solvent. Maybe CH2Cl2, CHCl3 (be careful, CHCl3 always contains EtOH!), CCl4, DiPE, MTBE, or di-t-butyl ether?
2. The randomly substituted versions (HPbCD, RAMEB) suffer many systematic errors.
2.1 If the DS (Degree of Substitution) is a substituent/glucopyranoside unit, the calculation error of MW of the CD derivative is high. If the DS is in traditional terms (as the pharmacopeias define, number of substituent/CD), the MW calculation might be better. It is recommended to record 1H-NMR (D2O is a good choice because, in DMSO, the water overlaps with the methyl /RAMEB/ or methylene /HPbCD/ signals) and calculate yourself. Both ways give average values, but the calculation errors are different.
2.2 An additional problem is the water content of both HPbCD (2-5%) and RAMEB (0.5-1%). Measure the water content by drying (covered with paper, 90-100 oC, vacuum, in the presence of KOH/P2O5, overnight). It is recommended for the bCD (14% water), too. The freshly dried bCD or HPbCD adsorbs water quickly.
2.3 Because these data are rounded values, the calculation errors might significantly affect the weighing.
3. Did you record the fluorescence of untreated and similarly treated (with the complex preparation) guests? Is there a difference between the fluorescence spectra of dichloride, monochloride, and dihydroxy silicone phthalocyanine?
4. Because of the reactivity of the guest, the CD substitution cannot be excluded, though it is less probable. Either the multisubstitution of a CD or connecting two CDs can change the fluorescence signal strength. So can the single or double Cl=>OH exchange.
Good luck,
Laszlo
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