9
3. Note that all drug (bioactive) molecules described in this chapter are acidic in nature and therefore neutralization takes place
at an alkaline pH between 9 and 10.5.
4. For the preparation of inclusion complexes in solid state using
the neutralization and freeze-drying technique, aqueous solutions of drug and CD should be prepared at the optimum molar
ratio for freeze-drying to follow.
5. In the described examples the optimum drug:CD molar ratio is
1:2 for the preparation of the aqueous solutions.
6. Aqueous solutions of drug and CD at a different drug:CD
molar ratio than 1:2 can also be used if needed. For example:
(a) Prepare SLB–2-HP-β-CD aqueous solutions for freezedrying in molar ratios of 1:1 and 1:4 following the steps
described in Subheading 3.5 but weigh accurately 930 mg
and 3720 mg of 2-HP-β-CD, respectively, and mix with
300 mg of SLB at a final volume of 300 mL [28].
(b) For the preparation of CAN− or CC−2-HP-β-CD aqueous solutions for freeze-drying in a molar ratio of 1:1 follow the procedure described in Subheading 3.3 but weigh
accurately 99.28 mg or 71.69 mg of 2-HP-β-CD and mix
with 30 mg of CAN or CC, respectively (accurately
weighed), at a final volume of 30 mL.
7. Freeze the prepare aqueous solution immediately at ≤−70 °C,
to avoid layering during freezing.
5 Conclusions
The neutralization and freeze-drying (or lyophilization) technique
can be successfully applied for the preparation of drug:CD inclusion complexes [25–31]. All the abovementioned example complexes prepared were confirmed to be adequately complexed with
CD through NMR and thermal analysis procedures in order to
evaluate the strength of inclusion and possible molecular structure,
while in all cases in vitro bioactivity was confirmed [25–31]. In
parallel, in vitro solubility and dissolution experiments were conducted to compare the complex developed against either the pure
drug or the reference marketed products and evaluate their possible bioavailability when orally administered [32–34].
Acknowledgments
This work was financially supported by the European Union and
Greek national funds through the program “Support for
Researchers with Emphasis on Young Researchers” (call code:
EDBM34, K.Ε. 14995, Preparation and Study of Novel Forms of
Neutralization and Freeze-Drying Technique to Prepare Drug: CD Complexes
3. Note that all drug (bioactive) molecules described in this chapter are acidic in nature and therefore neutralization takes place
at an alkaline pH between 9 and 10.5.
4. For the preparation of inclusion complexes in solid state using
the neutralization and freeze-drying technique, aqueous solutions of drug and CD should be prepared at the optimum molar
ratio for freeze-drying to follow.
5. In the described examples the optimum drug:CD molar ratio is
1:2 for the preparation of the aqueous solutions.
6. Aqueous solutions of drug and CD at a different drug:CD
molar ratio than 1:2 can also be used if needed. For example:
(a) Prepare SLB–2-HP-β-CD aqueous solutions for freezedrying in molar ratios of 1:1 and 1:4 following the steps
described in Subheading 3.5 but weigh accurately 930 mg
and 3720 mg of 2-HP-β-CD, respectively, and mix with
300 mg of SLB at a final volume of 300 mL [28].
(b) For the preparation of CAN− or CC−2-HP-β-CD aqueous solutions for freeze-drying in a molar ratio of 1:1 follow the procedure described in Subheading 3.3 but weigh
accurately 99.28 mg or 71.69 mg of 2-HP-β-CD and mix
with 30 mg of CAN or CC, respectively (accurately
weighed), at a final volume of 30 mL.
7. Freeze the prepare aqueous solution immediately at ≤−70 °C,
to avoid layering during freezing.
5 Conclusions
The neutralization and freeze-drying (or lyophilization) technique
can be successfully applied for the preparation of drug:CD inclusion complexes [25–31]. All the abovementioned example complexes prepared were confirmed to be adequately complexed with
CD through NMR and thermal analysis procedures in order to
evaluate the strength of inclusion and possible molecular structure,
while in all cases in vitro bioactivity was confirmed [25–31]. In
parallel, in vitro solubility and dissolution experiments were conducted to compare the complex developed against either the pure
drug or the reference marketed products and evaluate their possible bioavailability when orally administered [32–34].
Acknowledgments
This work was financially supported by the European Union and
Greek national funds through the program “Support for
Researchers with Emphasis on Young Researchers” (call code:
EDBM34, K.Ε. 14995, Preparation and Study of Novel Forms of
Neutralization and Freeze-Drying Technique to Prepare Drug: CD Complexes