Phase-solubility study
Phase-solubility studies were carried out by adding 100 mg of drug to screw-capped vials containing various concentrations
of a 25-mL aqueous HP–β –CD solution. The solutions were stirred continuously using an electromagnetic stirrer (Labstirrer,
Remi Laboratory Instruments, Mumbai) at 25 °C and 37 °C and 300 rpm for 48 h. The solutions were filtered through 0.45-µm
membrane filter. The filtrates were suitably diluted with simulated intestinal fluid at pH 6.8 simulated intestinal fluid
(SIF) and analyzed spectrophotometrically (Shimazdu-1601 ultraviolet-visible spectrophotometer, Shimadzu, Kyoto, Japan), for
the dissolved drug at 276 nm.
Preparation of complexes and physical mixtures. Solvent-evaporation method (coevaporation). An inclusion complex containing various weight ratios (i.e., 1:1, 1:2, and 2:1) of HP–β–CD to GLZ was prepared by the coevaporation
method (16). The appropriate amount of HP–β–CD was added to a solution of GLZ (500 mg) in 0.1 N NaOH (10 mL). Next, the solvent
was evaporated at 60 °C in an oven. The resulting residue was dried under vacuum at 40 °C for 3 h, ground in a mortar, and
passed through an 80# sieve.
Kneading method. The required quantities of HP–β–CD, GLZ, and 0.1 N NaOH (1.5 mL) were mixed together in a mortar to obtain a homogeneous
paste. GLZ was then added slowly. During grinding, a small quantity of 0.1 N NaOH (0.5 mL) was added to assist the dissolution
of GLZ. The mixture was then ground for 1h. During this process, an appropriate quantity of 0.1 N NaOH was added to the mixture
to maintain a suitable consistency. The paste was dried under vacuum at 50 °C for 24 h. The dried complex was pulverized and
sieved through an 80# sieve.
Physical mixtures. Physical mixtures (PMs) having the same weight ratios of HP–β–CD to GLZ (i.e., 1:1, 1:2, and 2:1) were prepared by thoroughly
mixing appropriate amounts of GLZ and HP–β–CD in a mortar until a homogeneous mixture was obtained.
Characterization of solid dispersion. Infrared (IR) spectroscopic analysis. FTIR spectra of moisture-free powdered samples were obtained using a spectrophotometer (FTIR-8300, Shimadzu) with the potassium-bromide
pellet method (i.e., a 5-mg sample in 200 mg of potassium bromide). The scanning range was 400–4000 cm-1 , and the resolution was 1 cm-1 .
DSC analysis. DSC scans of the powdered samples were recorded using DSC with Thermal Data Analyzer trend-line software (DSC 60, Shimadzu).
All samples were weighed and heated at a scanning rate of 10 °C/min under dry nitrogen flow (100 mL/min) between 50 and 300
°C. Aluminum pans and lids were used for all samples.
Solubility study
The complexes prepared by the kneading, coevaporation, and physical-mixture methods were assayed for GLZ content by the saturated
shaking-flask method (17). Excess amounts of the complex were placed into 10-mL vials containing water. The vials were sealed
and shaken for 24 h at room temperature. The solutions were filtered through a 0.45-µm membrane filter. The filtrates were
suitably diluted and analyzed spectrophotometrically for the dissolved drug at 276 nm. All assays were performed in triplicate.
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