Step 1: preformulation study for polymer selection
According to the literature reviewed, the pH in the proximal colon ranges from 6.6 to 7.0 (~6.8).6 A combination of acrycoat L 100 and S 100 was therefore designed to maintain the optimum pH. Accordingly, acrycoat L 100
(soluble in pH 6 and above) and acrycoat S 100 (soluble in pH 7 and above) were mixed in different ratios (1:1, 1:1.5, 1:2
and 1:3) and the final mixtures underwent solubility studies at pH 6.8. Based on the solubility parameters, we ascertained
that acrycoat L 100 and acrycoat S 100 at a ratio of 1:2 was highly soluble in pH 6.8. This combination was therefore selected
for the preparation of microcapsules.
Step 2: microcapsule preparation
The acrycoat microcapsules containing DS were prepared using emulsification-solvent evaporation in an oily phase. Accurately
weighed acrycoat L 100 and acrycoat S 100 in the ratio of 1:2 were dissolved in 10 mL of acetone to form a homogenous polymer
solution. Drug was separately suspended in the polymer solution, which was maintained in a continuous phase consisting of
70 mL of liquid paraffin, 1% (w/w) of span 80 and 0.01% (v/v) simethicon (as antifoaming agent) and was stirred constantly
at 1000 rpm using a variable speed propeller stirrer to form a uniform emulsion. Approximately 5–10 mL of acetone was added
to the external continuous phase to produce a stable oil/oil emulsion and then stirring was continued (3–4 h) until residual
acetone had evaporated. The microcapsules formed were separated by filtration, washed three to four times with nhexane to
remove adhering liquid paraffin, and dried for 48 h in a vacuum desiccator.
Four batches were prepared by varying the drug to polymer ratio (D:P=1:0.5, 1:1, 1:1.5 and 1:2 (w/w) named DM 1 to 4, respectively)
and evaluated for their flowability, particle size, drug content, surface morphology, compatibility and in vitro release profile.
Step 3: capsule preparation
The body and the cap of the hard gelatin capsules were separated. The body portion of the capsules was placed on a wire mesh
into a desiccator, which was then exposed to formaldehyde vapours for 6 h at room temperature and dried at 50 °C for 48 h
in a hot air oven. The treated capsule bodies were capped with untreated caps and stored at ambient conditions in a sealed
glass container.7
Step 4: capsule filling
The microcapsule formulation that had shown good drug content and release characteristics was placed into the capsule manually.
Microcapsules (D:P=1:1.5) equivalent to 100 mg of DS were incorporated into treated bodies of empty capsule shells and plugged
with different amounts (10, 15 and 20%) of hydrogel polymers; that is, NaCMC, GG, HPMC, HPCH and NaAlg.
Step 5: sealing and coating of capsules
The joint of the treated body and cap of the capsule was sealed with a small amount of the 5% w/v ethyl cellulose ethanolic
solution, and the filled and sealed capsules were then coated with CAP to ensure that drug release occurred in the colon rather
than in the stomach. The various parameters of coating conditions were standardized, such as dipping time (5 s), coating solution
concentration, temperature (25±10 °C) and drying time (5 min) at 500 °C. Coating was repeated until a 6–8% increase in weight
was obtained. The percentage weight gain of the capsules before and after coating was determined using Equation 1.
Where Wt is the weight of the capsules after coating, Wo is the initial weight of capsules. The capsules were dried in an oven at 50
°C for 12 h.
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