In vitro release profiles for microcapsules
Figure 3
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The in vitro release profiles obtained for the formulations are shown in Figure 3. It was observed that drug release from the microcapsules decreased with the increase in the amount of polymer added in each
formulation. As the amount of polymer in the formulation increased, the time required to swell also increased, thereby decreasing
the drug release. The release showed a biphasic release with an initial burst effect because of the imperfect entrapment of
drug into the microcapsule. In the first 30 min, drug release was 34.05%, 29.75%, 23.55% and 19.25% for DM1, DM2, DM3 and
DM4, respectively. The overall cumulative percent release for DM-1 to DM4 were 96.89%, 90.55%, 87.95% and 84.35% at the end
of 12 h, respectively.
Drug–excipient compatibility study
From the overlay FTIR spectra, we observed no changes of main peaks in the IR spectra of the mixture of drug and polymers,
which prove that there were no physical or chemical interactions between drug and polymers. Furthermore, the spectra obtained
from the formulation suggest that drug completely bound with the polymer to form the microcapsules. The spectra obtained from
the drug and drug–polymer physical mixture suggest that both drug and polymer showed a peak at around the requisite wave number,
thereby suggesting that there was no reaction between the drug and the excipients.
Formaldehyde treatment of hard gelatin capsule
Formaldehyde treatment was used to modify the solubility of the hard gelatin capsules. The solubility test was conducted for
normal capsules and formaldehydetreated capsules for 24 h. For the normal capsules, both cap and body dissolved within 15
min whereas, with the formaldehydetreated capsules, only the cap dissolved within 15 min, while the capsule body remained
intact for about 24 h. This insolubility indicates suitability for colon targeting.
Evaluation of Pulsincap dosage
Figure 4
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On the basis of drug content, particle size morphology, in vitro release and release kinetics, formulation DM3 was the better formulation for designing a pulsatile device. The results obtained
for all 15 formulations (F1–F15) are shown in Figure 4. The in vitro release profile was comparable for formulations F1–F3 (a), F4–F6 (b) and F7–F9 (c), F10–F12 (d), F13–F15 (e), which contains
NaCMC, GG, HPMCK4M, NaAlg and HPCH, respectively as hydrogel plugs at different proportions (i.e., 10, 15 and 20%).
During the dissolution studies, the outer coat, which was made by CAP for all batches remained intact for 2 h in pH 1.2 and
dissolved in intestinal pH, leaving the soluble cap of the capsule. The exposed polymer plug was then absorbed by the surrounding
fluid, swelled and released the drug through the swollen matrix. After complete wetting of the plug, it formed a soft mass,
which was easily ejected out of the capsule body; releasing the acrycoat microcapsules into SCF. With regard to the 10 and
15% hydrogel plug proportions, the polymer concentration was sufficient to retard the drug release in small intestinal fluid
and the plug ejected out in colonic fluid, releasing the entire drug in colonic pH, in a controlled manner. However, with
20% hydrogel plug proportions, a decrease in the expelling power of plug was observed, which might be the result of inadequate
wetting of the polymer.
Creativ Studio Heinemann/Getty Images
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The order of sustaining capacity of the polymers — GG HPMC>NaAlg NaCMC>HPC — was found on the basis of the tendency to produce
a soft swollen matrix and time required to eject from the capsule body. The release of drug from the modified pulsatile capsule
was proportional to the concentration of the polymer.
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