Quality Control Assessment on Comparative Study of Different Marketed Brands of Cetirizine Hydrochlorde Tablet

INTRODUCTION

Cetirizine hydrochloride is a second-generation antihistamine frequently utilized for the treatment of a range of allergic disorders. It is the hydrochloride salt form of cetirizine, which is a metabolite, derived from hydroxyzine, and is recognized for its effectiveness in alleviating symptoms related to allergies. [1]

Chemical structure:

Chemical formula: C21H25CIN203 2HCL [1]

IUPAC name: 2- [2- [4- [(4- chlorophenyl)-phenylmethyl] piperazin -1- yl] ethoxy] acetic acid dihydrochloride. [1]

Molecular weight: 388.89 g/mol [1]

Category: Antihistaminic [1]

Description: A white or almost white powder. [1]

Solubility:

It is very soluble in water, and slightly soluble in ethanol.

It is also soluble in organic solvents like dimethyl form amide and DMSO. [1]

Dose: 10 mg once daily. [1]

Cetirizine hydrochloride, a second – generation antihistamine, was introduced in the 1980s by the Belgian pharmaceutical firm UCB as a superior alternative to first – generation antihistamines, which frequently resulted in sedation. This medication, derived from hydroxyzine, was specifically formulated to selectively inhibit H1 histamine receptor, alleviating allergic symptoms such as itching, sneezing, and hives while minimizing drowsiness. It’s received its initial approval in Europe in 1987 and quickly became popular due to its effectiveness and safety profile. [5] In 1995 the U S food and Drug Administration (FDA) approved cetirizine, and it was launched under various brands names in 1996. Initially prescribed by healthcare professionals, it soon became a common treatment for allergic rhinitis and chronic urticarial. By 2007, the FDA classified cetirizine as an over-the-counter (OTC) medication, enhancing its availability to consumers. [7] Today, cetirizine is a fundamental component of allergy treatment, offered in forms such as tablets, and syrups. Renowned for its 24- hours’ effectiveness and mild side effect, including dry mouth and slight drowsiness, it continues to be a favored option for allergy relief globally. Its introduction represents a notable progress in antihistamine therapy, achieving a balance between efficacy and improved tolerability. [5] The objective of this study is to evaluate and compare various quality attributes, including physicochemical parameters such as weight variation, hardness, friability, disintegration time, and dissolution profile. This will be accomplished through a series of test conducted in accordance with approval protocols and established procedures for two different marketed brands of Cetirizine hydrochloride tablets.

METHOD AND MATERIAL:

Material-

The study utilized two different brands of Cetirizine hydrochloride tablets, each with a dosage of 10mg. The brands include are Okacet, produced by Cipla (A), and Cetzine, manufactured by Dr. Reddy`s(B). A range of tests is conducted to assess quality, including evaluation of general appearance, weight variation, content uniformity, thickness, hardness, friability, disintegration, and dissolution.

Equipment-

1.  Analytical balance
2.  Vernier caliper
3.  Hardness tester
4.  Friability
5.  Disintegration apparatus
6.  Dissolution apparatus 

Chemical and Reagent-

• 0.1 N HCL solution
• Cetirizine Hydrochloride Tablet
• Water

 Regent -0.1 N HCL Solution preparation: - 8.2gm HCL + 1000 ml of water.

METHODOLOGY -

Physical Characteristics-

The physical characteristics of the selected tablet, including size, shape, and sensory attributes such as taste and odor, were assessed through visual inspection and manual testing.

Thickness test -

Ten tablets from each brand were selected at random, and their thickness was measured using a Vernier caliper. The mean and standard deviation were subsequently calculated. [3]

Hardness test -

The tablet hardness test involves using a tablet hardness tester such as Monsanto, Pfizer. The Pfizer type tablet hardness tester is a widely used instrument in the pharmaceutical industry to measure the hardness (crushing strength) of tablets. It determines the force required to break a tablet, which is critical for insuring tablet quality, durability, and performance during handling, packaging, and dissolution. [3] Typically, ten tablets are tested, with an acceptable range of 4-10kg (40-100). [2]

Friability test -

The friability assessment for tablets is performed in a laboratory setting utilizing a Electrolab friabilator. Initially, twenty tablets are weighted and then placed into the friabilator, which operates at a speed of 25 revolutions per minute for a duration of four minute (100 Revolution). Following this process, the tablets are cleaned of any dust and weighed again. The change in weight from the initial to the final measurement is used to determine the friability, which is expressed as a percentage according to the following formula:

Friability = ((Initial weight - Final weight)/ Initial weight) * 100%.

Typically, conventional compressed tablets that exhibit a weight loss of less than 1% after undergoing 100 revolutions and deemed acceptable. [2]

Weight variation test -

The weight variation test is conducted to ensure the uniformity of dosage units (e.g., tablets, capsules) by measuring the weight variation among individual units. This test is crucial for confirming that each unit contains the intended amount of active pharmaceutical ingredient (API) and excipients, ensuring consistent dosing and efficacy. [2]

- Select a random 20 tablets from a batch.

- Weight each tablet individually using a calibrated analytical balance.

- Record the weight of each unit.

- Calculate the average weight of the units.

If the weight variation of all units falls within the specified limits by calculating lower and upper limit, the batch is considered to have passed the weight variation test.

If 2 tablet exceed the specified limits, the batch may be rejected, or further investigation may be required to determine the cause of the variation. [2]

Table 1 – Weight variation limits for film coated tablet according to IP [2]

Weight variation test is expressed in percentage.

Formula for weight variation test: -

Weight variation = (Iwi - Aw)/ Aw * 100%

Where,

Iw = Individual weight of tablet

Aw = Average weight of tablet.

Lower and upper limit formula-

Upper limit = Avg wt. + (limit / 100 * Avg wt.)

Lower limit = Avg wt. – (limit/100* Avg wt.)

Disintegration test -

The disintegration test assesses the rate at which tablets dissolve in a liquid environment, thereby ensuring the appropriate release of the drug within the body. In this procedure, a disintegration apparatus is utilized, where in six tablets of Cetirizine hydrochloride are positioned in tubes equipped with perforated discs and immersed in a medium, such as water, maintained at a temperature of 37± 2?. [2] The apparatus operates by moving the tubes in a vertical motion at a frequency of 28 to 32 cycles per minute. It is required that the tablets completely timeframe, typically ranging from 15 to 30 minute for uncoated tablets. Should 1 to 2 tablets not meet this criterion, the test is conducted again with an additional 12 tablets; all 18 must successfully disintegrate. A failure in this test may suggest potential problems related to the formulation, manufacturing process, or excipients, necessitating corrective measures. [3]

Dissolution test –

Dissolution test for film coated tablet according to IP by apparatus no .1 For the cetirizine hydrochloride tablet, a dissolution device containing a 1000 ml beaker was prepared with approximately 900ml of 0.1 M hydrochloride acid. One tablet of cetirizine was introduced into each beaker. An automatic heater was employed to maintain the temperature of the dissolving medium at 37±5 degree Celsius, with the stirring speed set to 100 revolutions per minute. Every five minute, 5ml of the solution was extracted from the beaker. A UV –visible spectrophotometer was utilized to measure the absorbance at a wavelength of 230nm. Ultimately, the percentage release of the cetirizine tablet was determined. [2]

RESULT AND DISCUSSION: -

The physicochemical characteristics of two different brands of cetirizine hydrochloride tablets are almost the same in their effects, suggesting that there is no significant difference between the two.

1. Physical Characteristic-

Cetirizine Hydrochloride tablets from two different brands have almost the same physical characteristic.

Table 2. Physical Characteristic

2.Thickness Test-

The thickness of cetirizine hydrochloride tablets was measured at 2.19mm (A), With an upper limit of 3.055mm and a lower limit of 2.7645mm, and 2.84mm(B), with an upper limit of 2.982mm and a lower limit of 2.698mm, as detailed in table 2. all cetirizine hydrochloride tablet were found to be within the permissible range (±5%) according to the Indian pharmacopoeia. The thickness assessment of tablets is a critical quality control measure in pharmaceutical production. It guarantees that each tablet is manufactured with uniform physical dimensions, which is essential for accurate dosing, compatibility with packaging, and overall consumer satisfaction. Factors such as formulation characteristics, particle size, and the compression force applied during production can influence tablet thickness. Inconsistencies in thickness may result in problem such as inadequate coating, challenges in packaging, and variations in weight and content uniformity. Ensuring uniform thickness is also vital for the tablets to dissolve and disintegrate at the intended rare, with is important for bioavailability and therapeutic effectiveness. Furthermore, controlling thickness helps mitigate mechanical damage during transport and handling. Tablets that are excessively thick or thin may not fit correctly into blister packs or containers, leading to logistical complication. Therefore, consistent monitoring of tablet thickness is essential for maintaining product quality, ensuring patient safety, and adhering to regulatory standards and specification.   

Table 3.  Thickness test

Figure 1. Thickness test

3.Hardness Test-

The hardness of cetirizine hydrochloride tablets was assessed, yielding of 6.11kg (A) and 4.56 kg (B). these results fall within the acceptable range of 4-10 kg as specified. The hardness test is a vital quality control procedure that evaluate the mechanical strength of the tablets, ensuring they can endure handling, packaging, and transportation without breaking or crumbling. This test measures the force necessary to fracture a tablet under pressure. Adequate hardness is crucial, as it guarantees that tablets are robust enough to resist physical damage while still being enough to disintegrate and dissolve effectively in the body, which is essential for proper drug release and absorption. Tablets that are too soft may fracture during packaging or handling, leading to dosage inaccuracies, whereas excessively hard tablets may fail to dissolve in the digestive system, diminishing their therapeutic effectiveness. Additionally, hardness testing aids in maintaining consistency across production batches and ensure adherence to pharmacopeial standards. Ultimately, this process enhances patient safety, product efficacy, and overall quality assurance in pharmaceutical manufacturing, making it a critical factor in tablet formulation and quality control.

Table 4. Hardness test

Figure 2. Hardness test

4.Friability Test-

The percentage friability of cetirizine hydrochloride tablets ranged from 0.200% (A) to 0.17%(B), as table 5. The proportion of friability should be less than 1%, under IP. Tested brands of cetirizine hydrochloride tablets met the friability standard since their percentage of friability was found to be less than 1%.As a result, the cetirizine hydrochloride tablets that were strong and resilient to handling and transportation shocks. A heightened risk of mechanical erosion, potentially leading to the depletion of the active ingredient and diminishing the drug`s efficacy, is linked to elevated friability level. As the hardness of the tablets increases, there is a significant reduction in the friability percentage across all formulation. Consequently, harder tablets will exhibit a lower friability percentage, while softer tablets will show the opposite trend. Additionally, variation in tablet weight or inconsistencies in content can be intensified by the propensity of tablet to crumble, which may also affect the visual appeal of the tablets and their acceptance by consumers.

Table 5. Percentage Friability

Figure 3. % Friability

5. Weight variation test-

Weight Variation test was conducted on two brands of Cetirizine Hydrochloride tablets, yielding results of 0.122 gm (A) with an upper limit of 0.131 gm and lower limit of 0.112 gm, and 0.115 gm (B) with upper limit of 0.124 gm and lower limit of 0.106 gm. This result was found to be within the acceptable limits established by the Indian Pharmocopoeia. The weight variation test serves a vital quality control measures in tablet production, ensuring that the weight of the tablet remains consistent within a defined range. Maintaining uniform tablet weight in crucial, as it directly affect the dosage of the active pharmaceutical ingredients (API) contained in each tablet. Significant weight discrepancies can result in either under dosing and overdosing, which can help in maintaining the safety and effectiveness of medication. Regulatory standards, such as those outlined in various pharmacopeias (USP, IP, BP) specified acceptable limits for weight variation based on the size of tablets. By ensuring consistent weight, manufacturers upload presion, product quality, and patient safety. A failure in weight variation test may cause manufacturing problems such as inadequate granule flow or improper filling of the die. Therefore, weight variation test is essential for pharmaceutical quality assurance and adherence to regulatory standard.

Table 6. Weight Variation Test

Figure 4. Weight Variation Test

6. Disintegration test-

The disintegration test for tablets was conducted, revealing a disintegration time of 10 min for formulation A and 8.50 min for formulation B. According to the standard set forth in Indian pharmacopoeia, coated tablets must disintegrate in less than 30 min, and both formulations were found to meet this requirement. To facilitate the removal of dissolution of the tablet coating, the tablet is immersed in distilled water for 5 min, followed by immersion in hydrochloric acid for 30 min at a temperature of 37?. If 1 to 2 tablets fail out of a sample of 6, the test should be repeated with an additional 12 tablets. A total of 16 out of 18 tablets must successfully pass the test. The disintegration test is a vital quality control measure that verifies whether a tablet can break down into smaller particles within a designated timeframe when exposed to a liquid medium. This process is critical as disintegration is the initial step leading to drug dissolution and absorption, which directly affects the drug's bioavailability and therapeutic efficacy. The main objective of the disintegration test is to replicate the conditions found in the gastrointestinal tract, ensuring that the tablet disintegrates appropriately after ingestion. Failure of a tablet to disintegrate may hinder the effective release of the active pharmaceutical ingredient (API), potentially rendering the medication ineffective or delaying its action. This is especially important for immediate-release formulations that require a rapid onset of action. Additionally, disintegration testing acts as a measure of formulation stability and consistency. Changes in excipients, compression force, or storage conditions can negatively impact disintegration time. Consequently, regular testing is essential to maintain uniformity across batches and ensure compliance with pharmacopeial standards such as those outlined in the USP, BP, or IP.

Table 7. Disintegration time

Figure 5. Disintegration test

7. Dissolution Test-

The tablet dissolution test is an essential quality control measure within the pharmaceutical sector. It evaluates the speed and degree to which the active pharmaceutical ingredient (API) is released from the tablet into a liquid environment, mimicking the conditions found in the human gastrointestinal system. This assessment is critical for confirming that the medication can be absorbed effectively in the body, which directly impacts its therapeutic efficacy. Consistent dissolution profiles indicate uniformity in production and batch quality, aiding in the identification of any variations in formulation or manufacturing processes. Additionally, this test is a fundamental requirement for regulatory submissions, as it demonstrates product performance and bioequivalence, especially for generic medications. Moreover, dissolution testing plays a significant role in stability studies, ensuring that the drug retains its effectiveness throughout its shelf life. Ultimately, it ensures patient safety and treatment effectiveness by verifying that each tablet releases the appropriate dosage of medication at the correct rate within the body.

Table 8. Dissolution Test

Figure 6. Dissolution Test