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Patil SV. et al. / International Journal of Biopharmaceutics. 2014; 5(1): 59-64.

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International Journal of Biopharmaceutics

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FORMULATION AND EVALUATION OF PROMETHAZINE HCl

FAST DISINTEGRATING SUBLINGUAL TABLETS
Patil SV*, Derle DV, Wagh SB
*
Department of Pharmaceutics, N.D.M.V.P Samaj’s College of Pharmacy,
Gangapur Road, Nashik-422002, Maharashtra, India.

ABSTRACT
This research work aims at developing fast disintegrating sublingual tablet of Promethazine HCl. Promethazine
HCl which is an antiemetic agent is primarily used to treat the symptoms of motion sickness i.e. nausea and vomiting during
travel or when in motion. The conventional tablet present in the market needs to be taken an hour before travelling, it
undergoes extensive hepatic first pass metabolism up to 75% thereby reducing its bioavailability to 25%. Hence a 10mg fast
disintegrating tablet was formulated by direct compression that can be administered sublingually to get rapid onset of action
without any first pass metabolism. A total 9 batches (PF1-PF9) were formulated using three superdisintegrants viz.
Crospovidone, L-HPC, and Kyron T-314 in three different concentrations. The tablets were prepared by direct compression
technique. All the batches were evaluated for thickness, hardness, friability, weight variation, in vitro Disintegration time,
in-vitro Dissolution time, % drug content, and content uniformity. The thickness of the batch from PF1-PF9 was found to be
3.12 - 3.32 mm and hardness was found to be 2.65 - 3.0kg/cm2 respectively. The friability, weight variation, and content
uniformity were found to be within the specified IP limits. All the tablets were found to disintegrate within 50 secs with PF3
tablets disintegrating in 18 secs. The tablets showed in vitro release upto 100 % within 30 mins with PF3 showing release
upto 96.05% within 10 mins. The drug content of all the nine formulations of Promethazine HCl tablets were found to be
within the range of 95.80-100.20 % and the average % drug content of tablets was found to be 99.52%. All the prepared
formulations (PF1-PF9) were found to be stable after 150 days at the prescribed storage conditions as per ICH guidelines
Q1A (R2) for Accelerated Stability testing.

Key words: Promethazine HCl, Sublingual tablet, Superdisintegrants.

INTRODUCTION nausea appears to be related to central anticholinergic

Promethazine HCl is a phenothiazine, an H1-
antagonist with anticholinergic, sedative, antiemetic
effects and some local anaesthetic properties. It is used as
an antiemetic to prevent motion sickness. Like other H1-
antagonist, Promethazine competes with free histamine
for binding at H1-receptor sites in the GI tract, uterus,
large blood vessels and bronchial muscle. The relief of
Corresponding Author
Patil SV
E-mail: dvderle@yahoo.com
actions and may implicate activity on the medullary
chemoreceptor trigger zone. The currently marketed
dosage forms of promethazine HCl include conventional
tablets, syrups and injections. The conventional
medication has slow onset of action, needs to be taken 1
or 2 hours prior to travelling and has to be swallowed
which requires water leading to incompliance with
patients of motion sickness. The syrup dosage form has
no precision over dose; high dosage may lead sedation,
drowsiness. Injections have quick onset of action but lack
patient compliance (Walton RP, 1935; Kurosaki Y et al.,
1991; Ghosh TK et al., 2005).

Patil SV. et al. / International Journal of Biopharmaceutics. 2014; 5(1): 59-64.
Hence, developing a mouth dissolving solid
dosage form which will give quick onset of action, no
swallowing, no water intake, and no bitter taste problems
etc will help to improve patient compliance in this
perspective. Promethazine HCl is lipophilic drug freely
soluble in water at pH 5-7.
The pKa value for Promethazine HCl is 9.1 and
dose is 10-25 mg for motion sickness. The sublingual
administration of Promethazine HCl means placement of
the drug beneath the tongue and drug reaches directly
into the blood stream through the ventral surface of the
tongue and floor of the mouth (Richman MD et al., 1965;
Boer D et al., 1984; Al‐Ghananeem AM et al., 2006;
Katz M and Barr M, 1955).
MATERIALS AND METHODS
All the materials used were of pharmaceutical
grade. Promethazine HCl was provided as a gift sample
by Ciron Drugs and Pharmaceuticals Ltd, Mumbai.
Crospovidone NF, Talc, Sucralose, and Mg-Stearate were
supplied by Glenmark Pharmaceuticals Ltd Nashik.
Kyron T-314 and L-HPC were provided as gift samples
by Corel Pharmachem, Ahmedabad and Arihant trading
company, Mumbai Respectively. Mannitol DC was
provided by Roquette Pharma Mumbai.
Experimental methods
Promethazine HCl fast disintegrating sublingual
tablets were manufactured in nine formulations viz. PF1
to PF9. The total weight of each tablet was kept constant
to 100 mg for all formulations. The drug and excipients
were passed through #60 sieve. Weighed amount of drug
and excipients were mixed in a polybag by geometric
addition method for 20 minutes manually. The blend was
RESULTS AND DISCUSSION
Drug-Excipient compatibility study
Stretching- 2800-3000 cm-1, NH+ stretching- 2200-2480 cm-1 , aromatic C=C stretching- 1591 cm-1, CH3 and CH2 bending-
1430-1470 cm-1, CH3 bending- 1378 cm-1, C-N stretching of tertiary amine-1334 cm-1,
60
then lubricated by further mixing with magnesium
stearate (#60 sieve). The mixture blend was subjected to
drying at 1050C for 3 hrs, the mixture was blended with
flavour and the powder blend was then compressed on 10
station rotary punching machine using round concave
punches. Round punches using 6mm diameter were used
for compression of tablets (Allen LV, 2003; The Drug
Bank, 2006).
Evaluation of Promethazine HCl sublingual tablets
Drug-Excipient compatibility studies
FT-IR spectroscopy was employed to
ascertain the compatibility between Promethazine
hydrochloride and the selected polymers. Potassium
bromide, pure drug and the polymers (Super
disintegrants) were heated to 105ºC for one hour to
remove the moisture content if present in a hot air oven.
Then in presence of IR lamp, potassium bromide was
mixed with drug and/or polymer in 9:1 ratio and the
spectra were taken. FT-IR spectrum of Promethazine HCl
was compared with FT-IR spectra of polymers.
Pre-compression parameters
These include Angle of Repose, Bulk Density,
Compressibility Index (Carr’s Index), Hausner ratio etc.
Post-compression parameters
The tablets after punching of every batch were
evaluated for in-process and finished product quality
control tests i.e. thickness, weight uniformity test,
hardness, friability, drug content, in vitro disintegration
time, wetting time and in vitro drug release studies
(British Pharmacopoeial Commission, 2009; The Indian
Pharmacopoeia Commission, 2007).
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b. FTIR spectra of Promethazine HCl + Crospovidone (1:1)

c. FTIR spectra of Promethazine HCl + Kyron T-314(1:1)

d. FTIR spectra of Promethazine HCl + L-HPC (1:1)

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Patil SV. et al. / International Journal of Biopharmaceutics. 2014; 5(1): 59-64.

Table 1. Composition of Promethazine HCl formulations PF1-PF9

F1-F9 Ingredients PF1 PF2 PF3 PF4 PF5 PF6 PF7 PF8 PF9
Sr No.
1 Promethazine HCl 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg
2 Crospovidone 2.5 mg 5 mg 7.5 mg - - - - - -
3 L-HPC - - - 5 mg 10 mg 15 mg - - -
4 Kyron T-314 - - - - - - 2.5 mg 5 mg 7.5 mg
4 Talc 1.0 mg 1.0 mg 1.0 mg 1.0 mg 1.0 mg 1.0 mg 1.0 mg 1.0 mg 1.0 mg
5 Sucralose 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg 3 mg
6 Mg-Stearate 0.5 mg 0.5 mg 0.5 mg 0.5 mg 0.5 mg 0.5 mg 0.5 mg 0.5 mg 0.5 mg
7 Flavour 2 mg 2 mg 2 mg 2 mg 2 mg 2 mg 2 mg 2 mg 2 mg
8 Mannitol(q.s) 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg

FTIR Interpretation of Promethazine HCl

Table 2. Various peaks obtained in the IR spectrum of Promethazine HCl
Sr no Wave number(cm-1) Vibration mode Peak obtained
1 2800-3000 CH stretching 2962.46
2 2200-2480 NH+ stretching 2358.78
3 1591-1650 Aromatic C=C stretching 1593.09
4 1430-1470 CH3 & CH2 bending 1456.16
5 1378 CH3 bending 1336.58
6 1220-1334 C-N stretching of tertiary amine 1228.57
7 850-860 Out of plane CH bending of 860.19
8 730-757 disubstituted aromatic group. 757.97

FTIR Interpretation of physical mixtures of Promethazine HCl with Crospovidone, L-HPC, and Kyron T-314.
Table 3. Various peaks obtained in the IR spectrum of Promethazine HCl with polymers
Sr. no IR Spectrum Wave number(cm-1) Vibration mode Peak obtained
1 Physical mixture of 2800-3000 CH stretching 2923.88
Promethazine HCl 2200-2480 NH+ stretching 2362.64
+ Crospovidone 1591-1650 Aromatic C=C stretching 1647..10
(1:1) 1430-1470 CH3 & CH2 bending 1456.16
1378 CH3 bending 1272.93
1220-1334 C-N stretching of tertiary amine 1228.52
850-860 Out of plane CH bending of disubstituted 860.19
730-757 aromatic group. 757.97
2 Physical mixture of 2800-3000 CH stretching 2921.96
Promethazine HCl 2200-2480 NH+ stretching 2362.64
+ L-HPC (1:1) 1591-1650 Aromatic C=C stretching 1593.09
1430-1470 CH3 & CH2 bending 1456.16
1378 CH3 bending 1334.65
1220-1334 C-N stretching of tertiary amine 1225.08
850-860 Out of plane CH bending of disubstituted 900.7
730-757 aromatic group. 757.97
3 Physical mixture of 2200-2480 NH+ stretching 2354.92
Promethazine HCl 1591-1650 Aromatic C=C stretching 1593.00
+ Kyron T-314 1430-1470 CH3 & CH2 bending 1456.16
(1:1) 1378 CH3 bending 1336.58
1220-1334 C-N stretching of tertiary amine 1228.50
850-860 Out of plane CH bending of disubstituted 845.7
730-757 aromatic group. 757.97
The principal peaks of Promethazine HCl were present in all the three FTIR spectras of crospovidone, L-HPC, and Kyron T-
314 with drug. This means that the above polymers do not interact with the drug and that the drug is compatible with these
excipients.
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Patil SV. et al. / International Journal of Biopharmaceutics. 2014; 5(1): 59-64.

Precompression parameters
.Table 4. Pre-compression parameters (values expressed as mean ± S.D where n=3)
Formulation Bulk Tapped Angle of Hausners
Carr’s Index % LOD
code density(g/cc) density(g/cc) repose(Ө) ratio
PF1 0.521±0.015 0.721±0.012 22.02±1.52 15.75±1.50 1.19±0.01 3.59±0.05
PF2 0.542±0.018 0.732±0.023 22.08±1.65 17.02±2.05 1.19±0.02 3.52±0.06
PF3 0.538±0.020 0.742±0.027 22.09±2.14 16.03±2.53 1.17±0.04 3.78±0.25
PF4 0.512±0.025 0.702±0.020 24.17±3.25 19.24±2.36 1.14±0.05 3.06±0.08
PF5 0.520±0.021 0.724±0.019 25.19±1.12 18.36±1.58 1.15±0.04 3.70±0.012
PF6 0.516±0.015 0.718±0.041 23.34±1.02 20.05±2.25 1.20±0.03 3.84±0.023
PF7 0.536±0.018 0.734±0.012 21.14±0.89 19.17±3.25 1.18±0.01 2.90±0.05
PF8 0.540±0.026 0.744±0.024 22.15±1.58 18.90±1.60 1.19±0.05 3.12±0.09
PF9 0.541±0.036 0.730±0.018 22.30±1.36 18.36±1.25 1.17±0.06 2.78±0.17

Table 5. Post-compression parameters (values expressed as mean ± S.D where n=3)

Formulation Thickness Hardness Friability Weight Disintegration Wetting
code (mm) (Kg/cm2) (%) variation (mg) time (Sec) time (Sec)
PF1 3.27±0.12 2.8±0.9 0.69 100.09±0.02 22±2.5 23±2.5
PF2 3.17±0.25 2.9±1.1 0.70 100.07±0.2 25±2.3 25±3.6
PF3 3.36±0.12 3.1±1.2 0.56 100.12±0.3 18±2.1 21±3.4
PF4 3.24±0.15 3.0±0.89 0.65 100.32±0.25 48±3.2 41±4.2
PF5 3.26±0.13 2.7±0.5 0.78 100.36±0.5 52±5.2 52±4.8
PF6 3.12±0.25 2.9±0.87 0.46 100.48±0.1 36±2.3 40±2.5
PF7 3.22±0.27 2.6±1.0 0.67 100.29±0.2 28±4.2 21±3.8
PF8 3.32±0.14 2.7±1.6 0.72 100.55±0.3 35±4.5 36±3.0
PF9 3.18±0.08 3.0±0.58 0.45 100.34±0.5 26±5.9 22±4.0
In vitro drug release profile
Table 6. Dissolution profiles of PF1-PF9
Time % Cumulative drug release for all formulations
(min) PF1 PF2 PF3 PF4 PF5 PF6 PF7 PF8 PF9
2 30.25 35.24 38.25 30.78 30.58 32.52 33.10 32.68 36.50
4 69.96 77.98 81.64 51.98 55.42 55.53 51.41 51.28 52.79
6 76.42 82.07 89.08 53.42 59.05 60.99 53.53 57.31 62.58
8 82.56 87.11 95.68 60.01 66.36 74.27 61.84 63.92 75.48
10 86.45 92.74 96.05 69.61 72.33 87.16 75.57 74.69 85.90
15 88.76 94.96 98.17 72.74 77.31 95.31 81.25 81.05 91.41
20 91.99 96.16 99.74 78.75 81.62 98.12 91.43 89.69 93.74
25 96.95 97.25 100.97 85.36 86.30 98.88 94.22 93.66 98.02
30 100.45 99.49 100.35 91.77 92.49 98.26 99.31 99.43 99.70

DISCUSSION namely Crospovidone, L-HPC, and Kyron T-314 were

In the present study, an attempt was made to
develop and evaluate rapid dissolving sublingual
tablets of Promethazine HCl (10mg) for better treatment
of vomiting especially for motion sickness. In general
Promethazine HCl having only 25% oral bioavailability
because of its high first pass metabolism rate. Thus,
formulated sublingual tablets of Promethazine HCl
prevents or avoids first pass metabolism and their
absorption directly takes place into the sublingual
mucosa which results in better oral bioavailability
compared to conventional Promethazine HCl tablets.
Nine different formulations of Promethazine
HCl with different concentrations of 3 superdisintegrants
formulated. Precompression and post compression
parameters were evaluated for all the nine formulations.
The formulation PF3 with Crospovidone (7.5%) was
found to be the most effective in terms of in-vitro
disintegration and in-vitro dissolution profiles.
Formulation PF5 was found to have 100.24 % drug
content (95-105%).
CONCLUSION
The Promethazine HCl tablets of strength 100
mg with different strengths of superdisintegrants were
formulated to target the symptoms of motion sickness.
Due to rapid disintegration and dissolution quick onset of
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Patil SV. et al. / International Journal of Biopharmaceutics. 2014; 5(1): 59-64.

action was achieved. MVP Samaj’s college of pharmacy, Nashik under the
guidance of Dr. D. V. Derle in the department of
ACKNOWLEDGEMENTS Pharmaceutics. I am thankful to all related authorities and
This work was carried out in the laboratories of personnel’s.

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