In vitro release profile of microcapsules
The in vitro dissolution profile of each formulation11 was determined using the USP Dissolution Apparatus 1 Basket method (900 mL of pH 6.8phosphate buffer, 100 rpm, 37±0.5 °C).
Microcapsules equivalent to 100 mg of drug were loaded into the basket (covered with Teflon cloth [porous polytetrafluoroethylene
(PTFE) cloth]) of the dissolution apparatus. Ten millilitres of the sample were withdrawn from the dissolution media at suitable
time intervals and the same amount was replaced with fresh buffer. Samples were filtered though a Whatman filter paper and
suitable dilutions were made when required. The absorbance of the samples was determined at the wavelength of 276 nm using
UV–Vis spectrophotometer, against pH 6.8 phosphate buffer as a blank. The amount of drug present in the filtrate was then
determined from the calibration curve, and cumulative percent of drug release was calculated.
A compatibility study was employed to assess the physicochemical compatibility between drug and the various excipients used
in the formulation.12 FTIR spectrums of drug, acrycoat S 100 and L 100polymer mixture, drug–polymer physical mixture and formulation were taken
and are reported in Figure 2.
Evaluation of designed pulsatile capsule
The polymer used in the Pulsincap dosage form should be able to swell to its maximum and eject from the capsule body in intestinal
fluid. The body portion of the capsules was subjected to disintegration studies at room temperature in a buffer solution of
pH 1.2, 7.4 and 6.8.
Ten capsules were selected randomly from each batch and weighed individually for weight variation.
In vitro release profile of the pulsatile capsule
Dissolution studies were performed using the USP Dissolution Apparatus 2 Paddle Method (900 mL of dissolution medium, 100
rpm, 37±0.5 °C). Capsules were tied to the paddle with a cotton thread in each dissolution vessel to prevent floating.13
To simulate the pH changes along the gastrointestinal tract, three dissolution media with pH 1.2 (simulated gastric fluid
(SGF) prepared by dissolving 2 g of NaCl and 3.2 g pepsin in 7 mL of HCl, and then adding deionized water (DW) to 1000 mL,
used for 2 h), 7.4 (simulated intestinal fluid (SIF) prepared by dissolving 6.8 g of monobasic potassium phosphate in 250
mL of DW, then adding 190 mL of 0.2 N NaOH, 400 mL of DW and 10 g of pancreatin, and finally adding 0.2 N NaOH to adjust the
pH to 7.4, and then diluting with DW to 1000 mL, used for 3 h) and 6.8 (simulated colonic fluid (SCF) prepared by adding 170
mL 1M acetic acid and 160 mL 1M NaOH in DW to 1000 mL, used for subsequent h) were used sequentially.14 Nine hundred millilitres of the dissolution medium was used at each time. Ten millilitres of the sample was withdrawn from
the dissolution media at suitable time intervals and the same amount was replaced with fresh buffer. Samples were filtered
though a Whatman filter paper and suitable dilutions were made when required. The absorbance of the samples was determined
at a wavelength of 276 nm using a UV–Vis spectrophotometer, against a respective buffer as a blank. The amount of drug present
in the filtrate was then determined from the calibration curve, and the cumulative percent of drug release was calculated.
Results and discussion
Physicochemical properties of DS microcapsules
The microcapsules of DM1 had a rough surface and the visible drug crystals on the surface indicated that the concentration
of the polymeric solution was insufficient for complete encapsulation. DM2 also had rough-surfaced microcrystals, but were
less crystalline than DM1. Some clumping of the microcapsules was observed in DM1 and DM2. DM3 and DM4 microcapsules were
uniform, spherical, smooth and discrete.
The mean particle size of the microcapsules significantly increased with the increase in polymer concentration. This was because
of the high viscosity of the medium at a higher polymer concentration resulting in enhanced interfacial tension and diminished
shearing efficiency.15 With regard to the size distribution data obtained from optical microscopy, when represented as lognormal distribution plots,
all four microcapsule formulations gave a straight line.
The angle of repose of four microcapsule formulations, shown in Table 1, exhibited good flow properties and the drug content was good in all cases, probably because of the adequate polymer concentration.
The remaining drug loss during the process can possibly be related to the partitioning of the drug to the oil phase.