In vivo disintegration studies.
The in vivo disintegration time was measured in six human volunteers. An RDF was placed on the tongues of the volunteers and time required
for disintegration in the mouth was noted.
In vitro dissolution studies.
In vitro dissolution studies were conducted using three dissolution media: distilled water (500 mL), simulated gastric fluid (900
mL), and simulated saliva (500 mL) (11). The studies were performed using USP dissolution apparatus XXIV (Electrolab, Mumbai,
India) at 37 × 0.5 °C and at 50 rpm using specified dissolution media. Each film with dimension (2 × 2 cm2 ) was placed on a stainless steel wire mesh with sieve opening 700 μm. The film sample placed on the sieve was submerged
into dissolution media. Samples were withdrawn at 2, 5, 10, 15, 30, 60, and 120 min time intervals, filtered through 0.45-μm
Whatman filter paper, and analyzed spectrophotometrically at 231 nm (UV 2450 Shimadzu Scientific Instrument, Kyoto, Japan).
To maintain the volume, an equal volume of fresh dissolution medium maintained at same temperature was added after withdrawing
samples. The absorbance values were converted to concentration using a standard calibration curve previously obtained by experiment.
The dissolution testing studies were performed in triplicate for all the batches.
Taste acceptability was measured by a taste panel with 10 mg drug and subsequently 10-mg film sample held in the mouth for
5–10 s, then spat out, and the bitterness level was recorded (6, 14). Volunteers were asked to gargle with distilled water
between the drug and sample administration. The following scale was used:
- + = very bitter
- ++ = moderate to bitter
- +++ = slightly bitter
- ++++ = tasteless or taste-masked.
Results and discussion
Fourier transfer infrared spectroscopy.
FTIR spectra of the pure drug showed significant bands at 3427, 2839, 2587, 1741, and 1600 cm–1, which indicates the presence of hydroxyl, ether stretching, tertiary amine salt, carbonyl groups, and phenyl nucleus skeletal
stretching, respectively, and confirms the purity of the drug.
Preliminary trials were undertaken for designing the RDF wherein the effects of various grades of HPMC namely E3, E5, and
E15 LV on the characteristics of the films were assessed. All three grades were varied in a concentration range of 1–4% w/v
(see Table I). The initial trials were taken to evaluate the suitability of various grades of HPMC for the formation of RDF
without addition of the drug.
In vitro disintegration time studies as shown in Table I suggested that films prepared with all three grades of HPMC had in vitro disintegration time below 30 s and were therefore acceptable.
Films prepared at 1% w/v concentration with all three grades were very thin, brittle, and easily broken. Films with 2–4% w/v
concentration for all three grades were clear, transparent, and easily separated. Therefore, further batches containing the
drug were formulated using 2–4%w/v of HPMC E grades.
RDFs containing 200 mg HPMC E5 LV formulated with CTZ resulted in highly brittle films compared with films containing 400
mg HPMC E5 LV, which separated easily. Thus, films containing 400 mg HPMC E5 LV were further evaluated for various parameters.
The reason for the brittle film formation in the presence of the drug using 200 mg HPMC E5 LV might be insufficient in the
sample required for film formation. The in vitro disintegration time of batches containing 400 mg HPMC E5 LV was acceptable (45 s). Trials were also conducted with the same
formulation in presence (containing 0.7 mg menthol per dose) and absence of menthol as a cooling agent and plasticizer. The
in vitro dissolution study of the above batches indicated total drug release in 10 and 30 min with and without menthol respectively.
Thus, the in vitro dissolution was found to be slightly extended.