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Vol 2 / Issue 1 / Jan - Mar 2023                                                                                      Indian J Pharm Drug Studies | 23  

Original Article   

Formulation and Evaluation of Rapidly Dissolving Film containing 

Antihistaminic drugs (Levocetirizine dihydrochloride)  

Vamakshi Thaker1, Jyoti Verma1, Suchita Waghmare1, Navinraj Mourya1  

From, 1Assistant Professor, School of Pharmacy, Rai University, Ahmedabad, Gujarat, India. 

Correspondence to: Vamakshi Thaker, Assistant Professor, School of Pharmacy, Rai University, Ahmedabad, Gujarat India. Email: 

vidhivamakshi@gmail.com  

ABSTRACT 

The oral dispersible tablets of Levocetirizine dihydrochloride were prepared by direct compression method. Various combinations of 

Sodium Starch Glycolate (SSG), Croscarmellose sodium (CCS) and Crospovidone (CP) were used as superdisintegrants for formulating 

the oral dispersible. It was seen that increasing the concentration of the superdisintegrants decreased the wetting time and disintegration 

time of the formulations. The combination of SSG & CP was more effective in decreasing the disintegration time as compared to the 

combination of SSG & CCS and CP & CCS. The in-vitro dissolution study showed that the formulation containing SSG (6%) and CP 

(4.5%) was more effective in enhancing the rate of drug release from the oral dispersible tablets.  The comparison of effect of individual 

superdisintegrant on wetting time, disintegration time and dissolution showed that SSG was more suitable for the formulation of oral 

dispersible tablets of Levocetirizine dihydrochloride as compared to other superdisintegrants used in the current study. Hence, from the 

present study, it can be concluded that the superdisintegrants SSG and CP in appropriate concentration can be used to develop oral 

dispersible tablets of Levocetirizine dihydrochloride by dire ct compression method. 

Key words: Orodispersible tablet, Superdisintegrants, Levocetirizine dihydrochloride, Surfactants, Starch, co-surfactants 

istamine is an organic nitrogenous compound 

involved in local immune responses, as well as 

regulating physiological function in the gut and 

acting as a neurotransmitter for the brain, spinal cord, and 

uterus. It consists of an imidazole ring attached to an 

ethylamine chain; under physiological conditions, the amino 

group of the side-chain is protonated [1].  

Properties: Histamine base, obtained as a mineral oil mull, 

melts at 83–84 °C. Hydrochloride and phosphorus salts form 

white hygroscopic crystals and are easily dissolved in water or 

ethanol, but not in ether. In aqueous solution, the imidazole 

ring of histamine exists in two tautomeric forms, identified by 

which of the two nitrogen atoms is protonated. The nitrogen 

farther away from the side chain is the 'tele' nitrogen and is 

denoted by a lowercase tau (τ) sign and the nitrogen closer to 

the side chain is the 'pros' nitrogen and is denoted by the pi (π) 

sign. The tele tautomer, Nτ-H-histamine, is preferred in 

solution as compared to the pro-tautomer, Nπ-H-histamine 

(Fig. 1) [2].   

Histamine has two basic centres, namely the aliphatic 

amino group and whichever nitrogen atom of the imidazole 

ring does not already have a proton. Under physiological 

conditions, the aliphatic amino group (having pKa around 9.4) 

will be protonated, whereas the second nitrogen of the 

imidazole ring (pKa ≈ 5.8) will not be protonated. Thus, 

histamine is normally protonated to a single charged cation. 

Histamine is a monoamine neurotransmitter [3].  

Synthesis and Metabolism: Histamine is derived from the 

decarboxylation of the amino acid histidine, a reaction 

catalyzed by the enzyme l-histidine decarboxylase. It is a 

hydrophilic vasoactive amine (Figure 2). Once formed, 

histamine is either stored or rapidly inactivated by its primary 

degradative enzymes, histamine-N-methyltransferase or 

diamine oxidase. In the central nervous system, histamine 

released into the synapses is primarily broken down by 

histamineN-methyltransferase, while in other tissues both 

enzymes may play a role. Several other enzymes, including 

MAOB and ALDH2, further process the immediate 

metabolites of histamine for excretion or recycling [4].  

Fig. 1 The tele tautomer (Nτ-H-histamine), on the left is 

more stable than the pros tautomer (Nπ-Hhistamine) on the 

right.  

H 



Thaker et al.                                                                    Formulation and Evaluation of Levocetrizine dihydrochloride 

Vol 2 / Issue 1 / Jan - Mar 2023                                                                                      Indian J Pharm Drug Studies | 24  

Fig. 2 -Conversion of histidine to histamine by histidine 

decarboxylase  

Bacteria also are capable of producing histamine using 

histidine decarboxylase enzymes unrelated to those found in 

animals. A non-infectious form of foodborne disease, 

scombroid poisoning, is due to histamine production by 

bacteria in spoiled food, particularly fish. Fermented foods and 

beverages naturally contain small quantities of histamine due 

to a similar conversion performed by fermenting bacteria or 

yeasts. Sake contains histamine in the 20–40 mg/L range; 

wines contain it in the 2–10 mg/L range [5].  

Mechanism of Action: In humans, histamine exerts its effects 

primarily by binding to G proteincoupled histamine receptors, 

designated H1 through H4. As of 2015, histamine is believed 

to activate ligandgated chloride channels in the brain and 

intestinal epithelium [6].  

Anti-Histaminic Drugs: Antihistamines are drugs which treat 

allergic rhinitis and other allergies. Typically, people take 

antihistamines as an inexpensive, generic, over-thecounter 

substitutes that can provide relief from nasal congestion, 

sneezing, or hives caused by pollen, dust mites, or animal 

allergy with few side effects. Antihistamines are usually for 

short-term treatment. Chronic allergies increase the risk of 

health problems which antihistamines might not treat, 

including asthma, sinusitis, and lower respiratory tract 

infection. Consultation by a medical professional is 

recommended for those who intend to take antihistamines for 

longer-term use [7]. Although people typically use the word 

“antihistamine” to describe drugs for treating allergies, doctors 

and scientists use the term to describe a class of drugs that 

opposes the activity of histamine receptors in the body. In this 

sense of the word, antihistamines are subclassified according 

to the histamine receptor that they act upon. The two largest 

classes of antihistamines are H1antihistamines and H2-

antihistamines.  

Classification of anti-histaminic drugs [8]  

H1-antihistamines: Meclizine, Clemastine, Hydroxyzine, 

Brompheniramine, Dimetindene, Doxylamine, etc. H2-

antihistamines: Loratadine, Cetirizine, levocetirizine, 

azelastine, fexofenadine, etc. H3-antihistamines: Ranitidine, 

Cimetidine, Famotidine, etc.  

Medical uses: Histamine produces increased vascular 

permeability, causing fluid to escape from capillaries into 

tissues, which leads to the classic symptoms of an allergic 

reaction- a runny nose and watery eyes. Histamine also 

promotes angiogenesis. Antihistamines suppress the 

histamine-induced wheal response (swelling) and flare 

response (vasodilation) by blocking the binding of histamine to 

its receptors or reducing histamine receptor activity on nerves, 

vascular smooth muscle, glandular cells, endothelium, and 

mast cells. Itching, sneezing, and inflammatory responses are 

suppressed by antihistamines that act on H1-receptors [9].  

Hence, for an antihistamine drug like Levocetirizine 

dihydrochloride, a quick-disintegrating dosage form is suitable, 

since the disintegration and dissolution of the dosage form 

occur rapidly, thus providing a rapid onset of action. It was 

thought worth formulating oro-dispersible a formulations of 

the drug, so that the patient can ingest the dosage form 

anywhere and at any time, without the aid of water, which 

would be helpful, especially in cases of unavailability of water, 

motion sickness, sudden episodes of allergic attacks, and 

deglutition problems. Mouth-dissolving tablets of 

Levocetirizine dihydrochloride were prepared by a direct 

compression method using different concentrations of spray-

dried mannitol (Perlitol SD 200), menthol, and camphor [10].  

Pharmacology: Levocetirizine is an antihistamine. It acts as 

an inverse agonist that decreases activity at histamine H1 

receptors. This in turn prevents the release of other allergy 

chemicals and increases the blood supply to the area, and 

provides relief from the typical symptoms of hay fever [11].  

Clinical Data  

• Trade Name :- LEVAZYL  

• Other name :- Levocetirizine dihydrochloride   

• Route of administration :-  By mouth  

Pharmacokinetics Data  

• Bioavailability :- High  

• Protein binding :- 90%  

• Metabolism :- Liver 14%  

• Elimination half-life :- 6 to 10 hour  

• Excretion :- Kidney and fecal  

Identification  

• IUPAC:-2-(2-{4[(R)-(4chlorophenyl) (phenyl)methyl] 

piperazine-1yl}ethoxy)  

• FORMULA :- C21H26ClN2O3   

• Molar mass :- 388.89 g.mol-1  

Plan of Work Formulation  

1. Materials:  Levocetirizine dihydrochloride was used as the 

active ingredient. Croscarmellose sodium, sodium starch 

glycolate and crosspovidone were used as the 



Thaker et al.                                                                    Formulation and Evaluation of Levocetrizine dihydrochloride 

Vol 2 / Issue 1 / Jan - Mar 2023                                                                                      Indian J Pharm Drug Studies | 25  

superdisintegrants. The other ingredients used were mannitol, 

aerosol, magnesium sterate, aspartame, mint flavor and 

microcrystalline cellulose PH 102. The active drug was 

obtained as a gift sample from SR Drug Laboratories Pvt. Ltd, 

Kathamandu. Crospovidone was received as a gift sample from 

Lomus Pharmaceuticals Pvt. Ltd, Kathmandu. The other 

excipients and chemicals used in experimental works were 

obtained from Nova Genetica pharmaceuticals Pvt. Ltd, 

Dhading, Nepal. All reagents used were of analytical grade [11].  

2. Methods: Preparation of orodispersible tablets of 

Levocetirizine dihydrochloride the composition of different 

formulations of Levocetirizine dihydrochloride orodispersible 

tablets. Levoretirizine dihydrochloride and all other excipients 

were weighed separately and passed through sieve number 60. 

The active drug was mixed with MCC PH102. Then the 

remaining excipients except the lubricants were blended with 

the active drug- MCC blend. The lubricants were then blended 

to the mix to form the final blend. The final blend was then 

compressed on a 10 stations rotary compression machine using 

an 8 mm punch.  

3. In-vitro wetting time studies:  Circular tissue papers of 

10cm diameter were placed in a petri-dish containing 10 ml of 

buffer solution simulating saliva, pH 6.8, and amaranth. A 

tablet was placed on the paper and the time taken to complete 

it wetting it was noted. Three tablets from each formulation 

were randomly selected and the average wetting time was 

recorded [12].  

4. In- vitro disintegration studies:  The disintegration time 

for all formulations was carried out using tablet disintegration 

test apparatus. Six tablets were placed individually in each tube 

of disintegration test apparatus and discs were placed. Water 

was used at the media for the study. The water was maintained 

at a temperature of 37°±0.5°C and time taken for the entire 

tablet to disintegrate completely was noted.  

5. In- vitro dissolution studies :  In vitro dissolution studies 

for all the fabricated tablets was carried out by using USP Type 

II apparatus (USP XXIII Dissolution Test Apparatus) at 50 

rpm in 900 ml of phosphate buffer pH 6.8, maintained at 

37±0.5ºC. 5 ml aliquot was withdrawn at the specified time 

intervals, filtered through Whatmann filter paper and assayed 

spectrophotometrically at 231nm using dissolution medium as 

blank. An equal volume of fresh medium, which was pre-

warmed at 370C was replaced into the dissolution medium 

after each sampling to maintain the constant volume 

throughout the test. Dissolution studies were performed in 

triplicate. Then the cumulative percentage of drug release was 

calculated using the following formula [12].  

Results & Evaluation  

1. Evaluation of films Thickness: All the batches were 

evaluated for thickness by using a calibrated digital 

micrometer. Three readings from all the batches were taken 

and the mean thickness was evaluated at 10.  

2. Folding endurance: The folding endurance was measured 

manually on the prepared films. A strip of film was cut and 

repeatedly folded in the same place till it broke. The number of 

times the film could be folded in the same place without breaking 

gave the value of folding endurance to 11.   

3. Drug content:  The drug content of all nine batches was 

determined by the UV-spectrophotometric method. For this, a 

1.4x1.2 cm2 strip from each batch was cut and dissolved in 

50ml of methanol. Then 5 ml of this solution was diluted to 50 

ml. So a 4ppm solution was made, filtered and absorbance was 

recorded at 231 nm in comparison with the 4ppm standard 

solution. Drug content was calculated by comparison method 10.  

4. Uniformity of drug content: For determining the 

uniformity of drug content in the film at least 10 strips (1.4x1.2 

cm2) ware taken and assayed. Same procedure was repeated 

for all the 6 batches 10.  

5. In vitro disintegration time: The disintegration test was 

performed on the USP disintegration time testing apparatus. 

Simulated salivary fluid (pH 6.8) was used as a medium. The 

films were placed in the tubes of the container and the disks 

were placed over it.  

6.  Bursting strength:  It is also known as tensile strength. It 

is the maximum tolerance power of an oral fast dissolving film. 

How many grams of weight when applied through a pointed 

subject in the film will be the bursting strength of that film?  

7. Moisture permeation: This test is to check weather a film 

is moisture permeable or not. For this in a vial desiccated silica 

was kept, and on the mouth of vial oral film was bounded and 

placed in 90% RH for 2 days.  

8. In-vitro dissolution studies: Dissolution study was carried 

out in USP basket type apparatus using the stimulated salivary 

fluid (pH 6.8) as a dissolution medium at 50 rotations per 

minute. 10 ml aliquots were withdrawn at one-minute time 

intervals and same amount of fresh dissolution medium was 

added. The aliquots were assayed for drug content at 231nm 

wavelength using UVspectrophotometer. The cumulative 

percentage drug release was calculated.  

DISCUSSION  

The comparison of the effect of individual superdisintegrants 

on the wetting time, disintegration time and dissolution showed 

that SSG was more suitable for the formulation of oral 

dispersible tablets of Levocetirizine dihydrochloride as 

compared to other superdisintegrants used in the current study. 

Hence, from the present study, it can be concluded that the 



Thaker et al.                                                                    Formulation and Evaluation of Levocetrizine dihydrochloride 

Vol 2 / Issue 1 / Jan - Mar 2023                                                                                      Indian J Pharm Drug Studies | 26  

superdisintegrants SSG and CP in appropriate concentration 

can be used to develop oral dispersible tablets of Levocetirizine 

dihydrochloride by direct compression method.  

CONCLUSION 

The oral dispersible tablets of Levocetirizine dihydrochloride 

were prepared by direct compression method. Various 

combinations of Sodium Starch Glycolate, Croscarmellose 

sodium and Crospovidone were used as the superdisintegrants 

for formulating the oral dispersible. It was seen that increasing 

the concentration of the superdisintegrants decreased the 

wetting time and disintegration time of the formulations. The 

combination of SSG & CP was more effective in decreasing 

the disintegration time as compared to the combination of SSG 

& CCS and CP & CCS. The in-vitro dissolution study showed 

that the formulation containing SSG (6%) and CP (4.5%) was 

more effective in enhancing the rate of drug release from the 

oral dispersible tablets.   

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How to cite this article: Vamakshi Thaker, Jyoti Verma, 

Suchita Waghmare, Navinraj Mourya. Formulation and 

Evaluation of Rapidly Dissolving Film containing 

Antihistaminic drugs (Levocetirizine dihydrochloride). 

Indian J Pharm Drug Studies 2023; 2(1) 23-26. 

Funding: None                      Conflict of Interest: None Stated 

 


