Wettability and dissolution studies
Wettability studies were performed using open tubes containing GLZ. Its PMs and inclusion complexes with HP–β–CD were placed
with their lower capillary ends dipped into a solution of 0.05% w/v crystal violet and water. The upward migration of the
colored front in the capillary tube was recorded as a function of time.
Dissolution studies were performed using Apparatus 2 of USP 30–NF 25 for 120 min. Samples equivalent to 5 mg of drug were added to the dissolution medium (i.e., 500 mL of demineralized water)
at a temperature of 37 °C ± 0.5 °C, which was stirred at 50 rpm. Operators withdrew 5-mL samples at intervals of 10, 20, 30,
40, 60, 90, and 120min. The samples were filtered with Whatman filter paper #1 (Whatman International, Maidstone, UK), diluted
with SIF, and analyzed at 276 nm using a spectrophotometer. The dissolution study was conducted in triplicate, and mean values
were plotted.
Formulation of an elementary osmotic-pump tablet
Table I: Formulation of elementary osmotic pump core tablet (%/tablet). ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHORS.
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Preparation of core tablet. The core tablets for the EOPT were prepared by direct compression. The GLZ complex was mixed with all the excipients and
passed through an 80# sieve. The formulation was compressed into tablets with an average weight of 310 ±20 mg on a multitooling
rotary tablet press (Remake Minipress-II MT, Karnavati Engineering, Kadi, India) fitted with 8-mm round, standard concave
punches. Table I lists various core formulations of the GLZ complex. The core tablets were evaluated for various pharmacotechnical
parameters.
Coating of core tablet. The core tablets were film coated with a semipermeable membrane of 2.5% w/v cellulose acetate (CA) with castor oil 20% (w/w
total weight of CA) as a plasticizer using a conventional, laboratory-model, stainless-steel, 20-cm, pear-shaped, baffled
coating pan with a pan-rotating rate of 25 rpm. Core tablets of GLZ were placed in the coating pan along with 100 g of filler
tablets made using 9.6-mm round concave punches and containing lactose, dibasic calcium phosphate, starch paste, magnesium
stearate, and talc. The inlet air temperature was about 60–70 °C. The manual coating procedure was used based on an intermittent
spraying and drying technique. The coated tablets were dried overnight at 50 °C to remove the residual solvent. An orifice
(500 µm) through the membrane was made by a mechanical driller.
In vitrodrug-release study of osmotic tablets.
In vitro drug release was tested according to the USP 30–NF 25 guidance for modified-release products. The authors used Apparatus 2 at 37 ± 0.5 °C and 50 rpm, testing 500 mL of 0.1
N HCl for the first two hours, followed by 500 mL of SIF. The samples were analyzed at 276 nm. The drug-release study was
conducted in triplicate, and mean values were plotted. For comparisons between dissolution profiles of different samples,
the authors used Moore and Flanner's model independent mathematical approach of calculating a similarity factor f
2
(18).
Scanning electron microscopy studies
Figure 1: Phase-solubility study.
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To characterize the surface of coated tablets before and after dissolution studies, the authors used a scanning electron microscope
(SEM). Before dissolution studies occurred, the sample coated tablets were examined for surface morphology by SEM (JSM-5600,
Jeol, Tokyo). A small sample of the coating membrane was carefully cut from the exhausted shells after 24 h of dissolution
studies and dried at 50 °C for 12 h. This sample was examined under SEM for surface-morphology changes after dissolution.
Results and discussion
Table II: Thermodynamic parameters of GLZ–HP–β–CD.
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Phase-solubility study. Figure 1 represents the effects of temperature on the solubility of GLZ in the presence of HP–β–CD. Table II shows the apparent
stability constants (Ka) and thermodynamic parameters derived from Figure 1.
The plots of drug solubility against the polymer concentration at the investigated temperatures indicate a linear relationship
in the investigated polymer concentration range. The solubility of GLZ increased with temperature and carrier concentration.
The solubility of GLZ in pure water at 25 °C was 39 µg/mL. At the highest polymer concentration (50 mM/mL), the solubility
increased approximately sixfold and fivefold at 37 °C and 25 °C, respectively.
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