Formulation and Characterization of Taste Mask Mouth Melt Film of Cetirizine HCl
Shaikh Samir K., Shashikant D. Barhate
Shri Sureshdada Jain Institute of Pharmaceutical Education and Research, Jamner, 424206.
*Corresponding Author E-mail: shaikhsamir07690769@gmail.com
ABSTRACT:
The goal of the present study is to formulate and characterize taste mask mouth melt film containing cetirizine HCl to improve therapeutic efficacy by improving patient compliance and convenience for both younger and older patients. Varied batches of mouth melt films (MMF) of cetirizine HCl were prepared by the solvent casting process using varied quantities of HPMC K15, PVP K30, cross povidone, sodium starch glycolate, sucralose, orange flavour, aspartame citric acid used for increases salivation and colour also used. The films were assessed for physical appearance, weight variation, thickness, folding endurance, surface PH, drug content, disintegration time. The best formulation CTR6 exhibited acceptable folding endurance (150±1.03), least disintegration time (20±0.51 seconds), highest drug content (98.50±0.72mg) as compare to other formulation batches. The study concludes that formulation CTR6 of Mouth Melt Films for sublingual delivery of cetirizine HCl may be a best formulation than the other batches. The formulated batch can be a unique dosage form to better disintegration rate, beginning of action, and patient compliance. The best formulation (CTR6) yields satisfactory results.
KEYWORDS: Mouth Melt, Solvent Casting Process, HPMC K15, Disintegrants, Taste Masking Agent.
INTRODUCTION:
Such a dosage form will be beneficial to the geriatric and pediatric patients, certain young individuals with underdeveloped muscular and nervous system, mentally ill and developmentally disabled patients, non-co-operative patients, people who are bed ridden, people who do not have access to water (e.g. travelers and army men)2. By introducing a novel and convenient method of drug administration, the fast-dissolving buccal film drug delivery system represents a significant advancement in drug administration. In order to develop a film that dissolves or disintegrates on the tongue or in the buccal cavity in one-minute, hydrophilic polymers are employed. This allows the medicine to dissolve and enter the bloodstream when it comes into contact with fluids3.
The MMF had advantages over other oral solid formulations, which included no difficulty in swallowing, disintegrating instantaneously, avoiding a situation of splitting large tablets and water not required for consumption.3,8 When compared with popular oral liquid dosage forms, the advantages of MMF included, accuracy in dose, minimal contact with mouth while administration, convenience in storage as well as transportation, no additional measuring cups or devices required and improved stability and taste4. Mouth Melt films and mouth-dissolving tablets are used for oral fast-dissolving doses, but mouth-dissolving tablets have drawbacks like choking and mouth residues. A new drug delivery system called Fast dissolving films/oral dispersible film/mouth dissolving films/oral disintegration film/oral dissolving film was developed to address these issues. This thin, postage stamp-sized film is applied to the patient's tongue or mucosal tissue, absorbing saliva to hydrate the area. The film quickly dissolves and disintegrates, releasing the medication for absorption by the oral mucosa. The dissolve time for orally dissolving films is typically 5 to 20 minutes, depending on the polymer used. The rapid onset of action occurs within seconds, as the medication is absorbed oro-mucosally and bypasses first-pass metabolism to reach the systemic circulation5. Different polymers, such as hydroxypropyl methylcellulose HPMC K15, polyvinylpyrrolidone PVP K30, have been successfully used in the preparation of mouth melt films 6. Apart from active pharmaceutical ingredients, the other components of mouth melt film are hydrophilic polymers, plasticizers, sweeteners, flavours, colours, preservatives etc.7. Mouth melt film rapidly disintegrates and dissolves to release the medication for Oro-mucosal and intragastric absorption8.
These new systems of drug transportation have become more and more popular in the scientific literature. Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosage forms. MMFs are manufactured to contain a precise drug load limited to 10 mg per MMF, which allows only medium-potency substances to be included9. These advantages have contributed to the widespread acceptance and popularity of this formulation, particularly among pediatric and geriatric patients and individuals with a fear of choking. Mouth melt films are now approved and utilized as a technique for achieving systemic distribution of active pharmaceutical ingredients (APIs) in over the counter (OTC) medications and some prescription treatments10. The pharmaceutical dosages are administered in the form of pills, granules, powders, and liquids. Generally, a pill is supposed to be swallowed intact or chewed to deliver a precise dose of medication to the patient. The pills, tablets, and capsules have the quality to retain their shapes under moderate pressure. Some patients, especially geriatric and pediatric groups face difficulty in swallowing solid dosage forms and have the risk of choking. To comfort such patients, a variety of fast-dissolving drug delivery modes have been developed11. The drugs absorb mostly through the gastrointestinal tract with saliva while a considerable part of it is absorbed through the mouth mucous into the blood. Thus, the first-pass hepatic metabolism is reduced and the bioavailability is enhanced12. Mouth dissolving films, a new drug delivery system for the oral delivery of the drugs, was developed based on the technology of the transdermal patch. The delivery system consists of a very thin oral strip, which is simply placed on the patient’s tongue or any oral mucosal tissue, instantly wet by saliva the film rapidly hydrates and adheres onto the site of application15.
Hence, based on the rationale of the proposed research work, the aim of present investigation was to formulate and characterize taste mask mouth melt films of cetirizine HCl using HPMC, PVP K30 by solvent casting method for direct drug absorption into the systemic circulation via transmucosal lining. Therefore, in the present work an attempt was made to formulate mouth melt films of cetirizine HCl for immediate release of drug for reducing the skin disease and potential to improve compliance and offers a number of competitive benefits over its marketed oral dosage forms.
MATERIALS AND METHODS:
Materials:
Cetirizine HCl was obtained from local market in Surat, Gujarat and HPMC K15, PVP K30, Crosspovidone, CMC, orange flavour, Sucralose, Aspartame, Citric Acid and Colour were collected in SSJIPER, Jamner 424206.
Methods:
Formulation of Mouth Melt Films of Cetirizine HCl: Mouth melt films were prepared by solvent casting method as per the composition shown in table below .In this method, the required quantity of water soluble HPMC, PVP K30, polymer was dissolved in distilled water in a beaker (covered with aluminium foil) with continuous stirring on magnetic stirrer to make required percentage of polymer solution and then the weighed quantity of ingredients like Cetirizine HCl as drug and, crosspovidone as a disintegrant, citric acid as a saliva stimulating agent, sucralose as sweetener and colour also were dissolved in distilled water in another beaker and then this mixture was added to the polymer solution. This solution is stirred continuously for 2 hours and then left undisturbed for 12-16 hours to let all air bubbles escape. Then this polymeric drug solution was poured on to the moulds, allowed to air dry and then packed in aluminium foil.
Table no. 1: - Formulation Batches of Mouth Melt Films of Cetirizine HCl:
|
Sr. No. |
Ingredients (mg.) |
Formulation Batches |
|||||
|
CTR1 |
CTR2 |
CTR3 |
CTR4 |
CTR5 |
CTR6 |
||
|
1. |
Cetirizine HCl |
10 |
10 |
10 |
10 |
10 |
10 |
|
2. |
HPMC K15 |
8 |
8 |
----- |
----- |
10 |
10 |
|
3. |
PVP K30 |
----- |
----- |
8 |
8 |
----- |
----- |
|
4. |
Crosspovidone |
----- |
----- |
4 |
4 |
5 |
6 |
|
5. |
CMC |
2 |
2 |
2 |
2 |
3 |
3 |
|
6. |
Sucralose |
0.5 |
0.5 |
0.5 |
0.5 |
1 |
1 |
|
7. |
Aspartame |
2 |
2 |
2 |
2 |
3 |
3 |
|
8. |
Citric Acid |
3 |
3 |
3 |
3 |
3 |
3 |
|
9. |
Mannitol |
5 |
5 |
5 |
6 |
6 |
6 |
|
10. |
Orange Flavour |
Q.S. |
Q.S. |
Q.S. |
Q.S. |
Q.S. |
Q.S. |
|
11. |
Colour |
Q.S. |
Q.S. |
Q.S. |
Q.S. |
Q.S. |
Q.S. |
Evaluation Parameters of prepared Mouth Melt Films:
Pre-Composition Parameters:
Melting point:
Digital melting point apparatus was used to determine the M.P. after the powdered drug was placed into a capillary tube with one side open and the remainder side sealed.3
Preparation of calibration curve of Cetirizine HCl:
Standard curve of cetirizine HCl in phosphate buffer pH 6.8 at 230nm was plotted using various concentrations against the absorbance values found at respective concentrations. The standard curve of cetirizine HCl was found to be linear in the range of 0-10µg/ml, which means that present drug sample was obeying Beers- Lamberts range (0-10µg/ml). The observations of calibration curve are shown in Table no. 2. The calibration curves of cetirizine HCl are shown in Figure no. 1.
Post-Composition Parameters:
All the Mouth Melt Films of Cetirizine HCl were subjected to following quality control tests.
1) Physical appearance and Surface Texture:
The Mouth Melt Films of Cetirizine HCl were subjected for determine the colour, Taste and Shape.1,10,26
2) Weight variation:
Mouths melt films were weighed on a digital balance, and the average weight was determined for each film. It is desirable that films should have nearly constant weight. It is useful to make sure that a film contains the right amount of excipients and API.2,11,18
3) Thickness of Films:
By using micrometer screw gauge, the thickness of the film was measured at 5 totally different places; an average of 3 values was calculated. This is essential to ascertain uniformity within the thickness of the film which is directly associated with the accuracy of dose within the film.2,13,23,26
4) Folding Endurance:
The number of folds necessary to break the specimen or create visible fissures is denoted as folding endurance. This demonstrates the film's brittleness. This test was performed on 2cm × 2cm films by folding the film at the same location many times until a breakage was observed.5,14,18,22
5) Surface pH:
The mouth melt film's surface pH is calculated to evaluate the probability of any in vivo adverse effects, as acidic or alkaline pH may cause irritation or inflammation to the oral mucosa, and it is assessed to keep the surface pH as close to neutral as possible. The film was placed in a petri plate and slightly moistened with 1 ml of distilled water for 30 seconds before measuring pH by bringing the electrode contacting the film's surface and allowing it to stand.6,15,19,24
6) Drug content uniformity:
Drug content uniformity was determined by dissolving the film (2×2 cm2) in 100ml of phosphate buffer PH 6.8 in 100ml of volumetric flask. Then the content was stirred on a magnetic stirrer, until the film dissolved. Then 5ml solution was taken and diluted, and the resulting solution was filtered through Whatman filter paper. The drug content was determined after proper dilution at 230nm using UV Visible spectrophotometer. 7,16,19,2
7) In vitro disintegration time:
The disintegration time was measured using the Petri dish method and is defined as the time (in seconds) at which a film begins to break or disintegrate. After placing the film in a Petri dish and adding 2 ml of phosphate buffer PH 6.8, the Petri dish was shaken constantly to determine the time at which the film began to break or disintegrate. The time it took to disintegrate the film was examined. 9,17,20,21
RESULT AND DISCUSSION:
Evaluation Parameters of Mouth Melt Films of Cetirizine HCl:
Pre-Composition Parameters:
1) Melting point:
The melting point of cetirizine HCl performed by using digital melting point apparatus and it was found in between 221 OC by capillary method.
2) Calibration curve of Cetirizine HCl:
Table no. 2: - Calibration curve of Cetirizine HCl
|
Sr. No. |
Concentration (µgm/ml) |
Absorbance (nm.) |
|
1. |
0 |
0 |
|
2. |
2 |
0.1253 |
|
3. |
4 |
0.2382 |
|
4. |
6 |
0.3663 |
|
5. |
8 |
0.4779 |
|
6. |
10 |
0.6089 |
Fig no. 1: - Calibration curve of Cetirizine HCl in Phosphate Buffer PH 6.8
Post-Composition Parameters:
1) Physical appearance:
Table no. 3: Physical appearance of Mouth Melt Film
|
Sr. No. |
Batches |
Colour |
Taste |
Shape |
|
1. |
CTR1 |
Orange, Transparent |
Like Orange |
Circular |
|
2. |
CTR2 |
Orange, Transparent |
Like Orange |
Circular |
|
3. |
CTR3 |
Orange, Transparent |
Like Orange |
Circular |
|
4. |
CTR4 |
Orange, Transparent |
Like Orange |
Circular |
|
5. |
CTR5 |
Orange, Transparent |
Like Orange |
Circular |
|
6. |
CTR6 |
Orange, Transparent |
Like Orange |
Circular |
DISCUSSION:
All films are clear, orange transparent, smooth and taste is orange and shape of films is circular.
2) Weight variation and Thickness:
Table no. 4: - Weight variation and Thickness of Mouth Melt Film
|
Sr. No. |
Batches |
Weight Variation |
Thickness |
|
1. |
CTR1 |
35.4±1.10 |
0.285±0.006 |
|
2. |
CTR2 |
33.8±1.25 |
0.135±0.007 |
|
3. |
CTR3 |
32.9±1.57 |
0.240±0.007 |
|
4. |
CTR4 |
30.11±1.01 |
0.248±0.006 |
|
5. |
CTR5 |
36.1±1.54 |
0.125±0.007 |
|
6. |
CTR6 |
35.1±1.54 |
0.110±0.008 |
All the values are expressed as mean±SD, n=3
DISCUSSION:
The average weights of 10 films were determined and the results are given in the Table 4. The weight variation was in the range of 30.11±1.01 to 36.1±1.54mg. Thickness of the film was measured with vernier caliper. The uniformity of the film thickness could be attributed to the accuracy of dose in the strip. As the concentration of the polymer increased, the thickness was gradually increased. The film thickness ranged from 0.110±0.008 to 0.285±0.006 mm (Table 4).
3) Folding Endurance and Surface PH:
Table no. 5: Folding Endurance and Surface PH of Mouth Melt Film
|
Sr. No. |
Batches |
Folding Endurance |
Surface PH |
|
1. |
CTR1 |
128±1.51 |
6.59±0.04 |
|
2. |
CTR2 |
117±1.60 |
6.60±0.03 |
|
3. |
CTR3 |
128±1.04 |
6.98±0.05 |
|
4. |
CTR4 |
139±2.00 |
6.92±0.05 |
|
5. |
CTR5 |
115±2.58 |
6.70±0.31 |
|
6. |
CTR6 |
150±1.03 |
6.81±0.07 |
All the values are expressed as mean ±SD, n=3
DISCUSSION:
The value of folding endurance was in the range of 115±2.58 to 115±2.58 result was given on Table no. 5. It was observed that with increase in concentration of polymer the folding endurance also increased. Higher the value of folding endurance, lower is the chance of film to rupture. The surface pH was measured to determine the possibility of any in vivo side effects, as the acidic or alkaline pH may cause oral mucosal irritation. The surface pH of the strips was ranging from 6.59±0.04 to 6.98±0.05 as shown in Table 5. The surface pH values of films assured that there will be no irritation to the oral mucosal lining.
4) Drug Content Uniformity and In-vitro Disintegration Time:
Table no. 6: - Drug Content Uniformity and In-vitro Disintegration Time of Mouth Melt Film
|
Sr. No. |
Batches |
Drug Content Uniformity (%) |
In-vitro Disintegration Time (Sec.) |
|
1. |
CTR1 |
91.51±0.10 |
28±0.76 |
|
2. |
CTR2 |
94.02±0.07 |
27±0.90 |
|
3. |
CTR3 |
89.90±0.50 |
29±0.36 |
|
4. |
CTR4 |
90.54±0.11 |
28±1.00 |
|
5. |
CTR5 |
95.21±0.11 |
24±0.76 |
|
6. |
CTR6 |
98.50±0.72 |
20±0.51 |
All the values are expressed as mean±SD, n=3
Fig. no. 2: In-vitro Disintegration Time of Mouth Melt Film of Cetirizine HCl
DISCUSSION:
The drug content uniformity in various formulations ranged from 89.90±0.50 to 98.50±0.72. The drug content was found to be within limit. The disintegration time of film was in range of 20±0.51 to 29±0.36 sec. as given in Table 6. As the concentration of Crosspovidone increased, the rate of disintegration also increased as shown in Figure no. 2.
CONCLUSION:
Mouth melt film of cetirizine HCl is an innovative dosage form that is having great importance in emergency situations like allergic condition such as skin rashes, urticaria, dry skin, and skin disease attacks where an immediate onset of action is required. The film prepared by two types of film former or polymer with in various concentration such as HPMC K5, PVP K30 and two types of sweetening agent and flavouring agent to mask the film of cetirizine HCl such as sucralose and orange flavour to (CTR6) was selected as the best formulation based on various evaluation parameters. The disintegration time of prepared best formulation showed a good disintegration time within 30 sec. which exhibit that it would provide an immediate relief from allergic reactions such as skin rashes, urticaria, dry skin, and skin disease due to its faster absorption in oral cavity and is a better alternative to conventional dosage forms. It can be concluded that the mouth melt film of Cetirizine HCl could be a promising approach for the treatment of allergy by overcoming the drawbacks associated with conventional and traditional types of dosage forms like tablets and capsules.
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Received on 20.12.2024 Revised on 23.01.2025 Accepted on 19.02.2025 Published on 27.02.2025 Available online from March 05, 2025 Asian J. Pharm. Tech. 2025; 15(1):34-38. DOI: 10.52711/2231-5713.2025.00006 ©Asian Pharma Press All Right Reserved
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