167
was applied on the raw materials of cyclodextrin and losartan, in
order to analyze them alone or in mixtures, as well as on a complexed form between the cyclodextrin and each sartan.
1. Dissolve 2-HP-β-CD and losartan potassium in purified water
separately, both at a concentration of 8 mg mL
−1
.
2. Freeze the solutions at −80 °C overnight (see Note 3).
3. Lyophilize samples with any appropriate lyophilizer, under the
following conditions: condenser temperature −50 °C; vacuum
8.2 × 10
−2
mb; and duration 24 h.
4. Store the lyophilized powders at 4 °C.
1. Transfer 6783.62 mg of 2-HP-β-CD in a glass vessel with
800 mL of purified water and set under magnetic stirring.
2. When the cyclodextrin is totally dissolved, add irbesartan or
losartan in the vessel and continue magnetic stirring (see Note
4). The molar ratio between cyclodextrin and either drug is
3.6:1 and usually the drug used is ca 1000 mg.
3. Adjust pH at approximately 10.5 with NH 3 5 N and the reaction of enclosure takes place.
4. When the solution is clear, fix the final volume at 1000 mL with
purified water and immediately freeze the solution of the complex at −80 °C for lyophilization to follow.
1. Prepare each sample for DSC analysis by weighting roughly
3 mg of dry powder that contains one or more components
inside a 40 μL aluminum crucible with O-ring (see Note 5).
2. Seal each crucible by using a sealing press, in order to make a
hermetic pan, and leave it to rest for a 15-min period, in order
to achieve equilibration of the sample (see Note 6).
1. Obtain the DSC thermogram of each sample by utilizing any
appropriate DSC calorimeter.
2. Calibrate the calorimeter with pure indium (T m = 156.6 °C)
before analyses, by applying a single heating cycle and checking
the characteristic transition temperature T m and enthalpy change
ΔH to be within specifications.
3. Include for each analysis a 5-min isotherm at 10 °C (see Note 7)
and a heating process from 10 °C to 230 °C for irbesartancontaining samples and 10 °C to 300 °C for losartan- containing
samples (see Note 8), at a heating rate of 10 °C min
−1
(see Note
9), under constant nitrogen gas flow rate of 50 mL min
−1
(see
Note 10).
3.1 Lyophilization
of Raw Materials
3.2 Complexation
of the Sartans
with 2-HP-β-CD
3.3 DSC Sample
Preparation
3.4 DSC Analysis
DSC on Sartan/Cyclodextrin Delivery Formulations
was applied on the raw materials of cyclodextrin and losartan, in
order to analyze them alone or in mixtures, as well as on a complexed form between the cyclodextrin and each sartan.
1. Dissolve 2-HP-β-CD and losartan potassium in purified water
separately, both at a concentration of 8 mg mL
−1
.
2. Freeze the solutions at −80 °C overnight (see Note 3).
3. Lyophilize samples with any appropriate lyophilizer, under the
following conditions: condenser temperature −50 °C; vacuum
8.2 × 10
−2
mb; and duration 24 h.
4. Store the lyophilized powders at 4 °C.
1. Transfer 6783.62 mg of 2-HP-β-CD in a glass vessel with
800 mL of purified water and set under magnetic stirring.
2. When the cyclodextrin is totally dissolved, add irbesartan or
losartan in the vessel and continue magnetic stirring (see Note
4). The molar ratio between cyclodextrin and either drug is
3.6:1 and usually the drug used is ca 1000 mg.
3. Adjust pH at approximately 10.5 with NH 3 5 N and the reaction of enclosure takes place.
4. When the solution is clear, fix the final volume at 1000 mL with
purified water and immediately freeze the solution of the complex at −80 °C for lyophilization to follow.
1. Prepare each sample for DSC analysis by weighting roughly
3 mg of dry powder that contains one or more components
inside a 40 μL aluminum crucible with O-ring (see Note 5).
2. Seal each crucible by using a sealing press, in order to make a
hermetic pan, and leave it to rest for a 15-min period, in order
to achieve equilibration of the sample (see Note 6).
1. Obtain the DSC thermogram of each sample by utilizing any
appropriate DSC calorimeter.
2. Calibrate the calorimeter with pure indium (T m = 156.6 °C)
before analyses, by applying a single heating cycle and checking
the characteristic transition temperature T m and enthalpy change
ΔH to be within specifications.
3. Include for each analysis a 5-min isotherm at 10 °C (see Note 7)
and a heating process from 10 °C to 230 °C for irbesartancontaining samples and 10 °C to 300 °C for losartan- containing
samples (see Note 8), at a heating rate of 10 °C min
−1
(see Note
9), under constant nitrogen gas flow rate of 50 mL min
−1
(see
Note 10).
3.1 Lyophilization
of Raw Materials
3.2 Complexation
of the Sartans
with 2-HP-β-CD
3.3 DSC Sample
Preparation
3.4 DSC Analysis
DSC on Sartan/Cyclodextrin Delivery Formulations