8
3. After complete dissolution a yellow solution is obtained.
4. Fix the final volume of the obtained solution at 150 mL with
purified water.
5. Immediately freeze this solution at −80 °C (see Note 7).
6. Freeze-dry the iced product to obtain a yellow solid state of the
CRM–2-HP-β-CD inclusion complex.
1. For the preparation of QUE–2-HP-β-CD aqueous solutions for
freeze-drying in a molar ratio of 1:2, mix 30 mg of QUE and
306 mg of 2-HP-β-CD, accurately weighed in a 50 mL beaker
(see Notes 4–6).
2. Suspend the mixture of solids with 20 mL of purified water.
3. The pH value should be adjusted at approximately 9–9.5 with
the help of ammonium hydroxide solution (5% v/v) under continuous magnetic stirring (see Notes 1–3).
4. After complete dissolution fix the volume of the obtained solution (1:2 QUE:CD molar ratio) to 60 mL.
5. Freeze the obtained orange-colored solution at −80 °C (see
Note 7).
6. Freeze-dry the final iced product to remove water and obtain
the final solid-state yellowish QUE–2-HP-β-CD inclusion
complex.
1. For the preparation of QUE–Me-β-CD aqueous solution for
freeze-drying in a molar ratio of 1:1, mix 2200 mg of Me-β-CD
and 500 mg of QUE, accurately weighed, into a glass vessel (see
Notes 4–6).
2. Suspend the mixture of solids with 400 mL of purified water.
3. The pH value should be adjusted at approximately 9–9.5 with
the help of ammonium hydroxide solution (5% v/v) (see Notes
1–3).
4. After complete dissolution, fix the volume of the obtained solution (1:1 QUE:CD molar ratio) to 500 mL.
5. Freeze the obtained orange-colored solution at −80 °C (see
Note 7).
6. Freeze-dry the final iced product to remove water and obtain
the yellow solid-state QUE–Me-β-CD inclusion complex.
4 Notes
1. The neutralization method [13] is applied prior to lyophilization (freeze-drying) to facilitate drug dissolution.
2. pH monitoring is important during the preparation of the
drug-CD aqueous solution, to maintain up to 10.5 and avoid
CD decomposition.
3.7 Steps to Follow
for the Preparation
of Solid-State QUE–2HP- β-CD and QUE–
Me-β-CD Inclusion
Complexes [29–31]
3.7.1 QUE–2-HP-β-CD
Inclusion Complex [29, 30]
3.7.2 QUE–Me-β-CD
Inclusion Complex [31]
Eirini Christodoulou et al.
3. After complete dissolution a yellow solution is obtained.
4. Fix the final volume of the obtained solution at 150 mL with
purified water.
5. Immediately freeze this solution at −80 °C (see Note 7).
6. Freeze-dry the iced product to obtain a yellow solid state of the
CRM–2-HP-β-CD inclusion complex.
1. For the preparation of QUE–2-HP-β-CD aqueous solutions for
freeze-drying in a molar ratio of 1:2, mix 30 mg of QUE and
306 mg of 2-HP-β-CD, accurately weighed in a 50 mL beaker
(see Notes 4–6).
2. Suspend the mixture of solids with 20 mL of purified water.
3. The pH value should be adjusted at approximately 9–9.5 with
the help of ammonium hydroxide solution (5% v/v) under continuous magnetic stirring (see Notes 1–3).
4. After complete dissolution fix the volume of the obtained solution (1:2 QUE:CD molar ratio) to 60 mL.
5. Freeze the obtained orange-colored solution at −80 °C (see
Note 7).
6. Freeze-dry the final iced product to remove water and obtain
the final solid-state yellowish QUE–2-HP-β-CD inclusion
complex.
1. For the preparation of QUE–Me-β-CD aqueous solution for
freeze-drying in a molar ratio of 1:1, mix 2200 mg of Me-β-CD
and 500 mg of QUE, accurately weighed, into a glass vessel (see
Notes 4–6).
2. Suspend the mixture of solids with 400 mL of purified water.
3. The pH value should be adjusted at approximately 9–9.5 with
the help of ammonium hydroxide solution (5% v/v) (see Notes
1–3).
4. After complete dissolution, fix the volume of the obtained solution (1:1 QUE:CD molar ratio) to 500 mL.
5. Freeze the obtained orange-colored solution at −80 °C (see
Note 7).
6. Freeze-dry the final iced product to remove water and obtain
the yellow solid-state QUE–Me-β-CD inclusion complex.
4 Notes
1. The neutralization method [13] is applied prior to lyophilization (freeze-drying) to facilitate drug dissolution.
2. pH monitoring is important during the preparation of the
drug-CD aqueous solution, to maintain up to 10.5 and avoid
CD decomposition.
3.7 Steps to Follow
for the Preparation
of Solid-State QUE–2HP- β-CD and QUE–
Me-β-CD Inclusion
Complexes [29–31]
3.7.1 QUE–2-HP-β-CD
Inclusion Complex [29, 30]
3.7.2 QUE–Me-β-CD
Inclusion Complex [31]
Eirini Christodoulou et al.