I'm currently working on the best way to solubilize Bilastine using Beta-Cyclodextrin. I have been reading a lot of Journals and Patents about it, but the best Journal I found (10.1016/j.carres.2008.10.025) explains that the optical pH to solubilize Beta-Cyclodextrin es at pH aprox. 12 (0.01M OH-), but I´m still wondering the correct procedure to do it.
Procedure 1. (Already tested and worked fine)
1. pH=12
2. Solubilize Beta-Cyclodextrin
3. Add Bilastine
4. Reach desire pH
or
Procedure 2. (Haven´t tested)
1. pH=12
2. Solubilize Beta-Cyclodextrin
3. Reach desire pH
4. Add Bilastine
I would like to read a Journal that provides me how easy or difficult is to follow procedure No. 2 or any advises would be welcome.
Tx
Hi Lester,
- Firstly, I am unsure whether a pH>12 system is suitable for oral administration. Try to use neutral or moderately acidic (pH~ 4-5.5) conditions.
- Secondly, the high pH will soon result in a significantly lower pH due to the CO2 adsorption capacity of the solid.
- The third comment is that the structure of bilastine is not optimal for ßCD. If it forms complex(es) at all, the 2:1 CD/Bilastin composition seems most likely.
- The fourth is your objective. If you want to make a soluble complex, ßCD may not be the optimal host. Although complex formation, at even neutral pH, can increase the concentration of ßCD in the solution, the molecular weight differences between the host and guest rarely allow a homogeneous solution at the targeted concentration levels.
In general, the higher pH is rarely favorable for complex formation. It is not impossible, but not optimal. It is partly due to the accumulation of negative charges and counterions, especially alkali metal ions, around the CD cavity. The consequence of crowding is a reduced ability of CD to form complexes. Since the pK of the primary hydroxyls is much higher (~15), a primary-side approach would be possible in principle but is much less likely due to the geometry of the bilastine molecule.
From your question, one can infer a soluble or a readily soluble complex. Geometrical reasons would favor gamma-CD, and since it is highly soluble in water and the shelf-dry compound contains only ~10% water, the preparation of a soluble complex seems possible.
Bilastine is not too insoluble at pH 4-5 (about 1%, or ~0.02 M), and CDs are still stable at this pH. I would propose using gCD at pH 4.5-5, in a 2:1 molar ratio (gCD/bilastine).
I would use the following protocol:
1. Dissolve gCD in deionized/distilled water (calculated gCD amount: 2 moles of bilastine).
2. Add the solid bilastine to the solution at room temp (I assume it is in neutral form) with vigorous stirring; if you are lucky, you will get a homogeneous solution and GoTo 4.
3. Add HCl to the suspension to adjust the pH between 4.5-5.
4. Remove any eventual solid residuals with a hydrophilic membrane (
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