Microsoft Word-z319 Development and Stability Enhancement of Two Combine Drugs of Cetirizine and Ambroxol

Ambroxol Hydrochloride and Cetirizine Hydrochloride are often prescribed together for greater patient acceptability, increased potency, multiple activity, fewer side effects and quick relief. Ambroxol Hydrochloride and Cetirizine Hydrochloride are used for the treatment of bronchitis, cough, and allergy. Ambroxol and Cetirizine tablet available in the market are not suitable in certain cases such as motion sickness, sudden episodes of allergic attacks, or coughing and when drinking water is not available. Particularly these types of difficulty are pediatric and geriatric patients. An attempt has been made to develop and enhance the stability of two combine drugs Ambroxol Hydrochloride and Cetirizine Hydrochloride, we prepared fast disintegration tablets. Total six formulations (F1 were prepared to study the effect of superdisintegrants shown in Table I. Tablets were prepared technique of direct compression methods quantity of each ingredient was taken for each specified formulation. The superdisintegrant, sodium starch glycolate (1%, 2%, 4%, 6%, 8%, and 10%) concentration was used to develop the tablets. All the ingredients were passed through mesh the ingredients were cogrind in a pestle motor. talc and Sodium Stearyl fumarate were added and mixed for 5 minutes. The blended excipients were compressed into tablets using tablet compression machine (Madhur Industries, India). The dissolution studied results revealed that in both of the drug Ambroxol Hydrochloride and cetirizine hydrochlori in phosphate buffer pH 6.8 and pH 7.4 dissolution medium were shown within the specified Pharmacopoeias limit. | Volume – 2 | Issue – 4 | May-Jun 2018 6470 | www.ijtsrd.com | Volume Journal of Trend in Scientific and Development (IJTSRD) International Open Access Journal and Stability Enhancement of Cetirizine and Ambroxol *, Tulshi Chakraborty, Vipin Saini ullana, Ambala, Haryana, India


Ambroxol
Hydrochloride and Cetirizine Hydrochloride are used for the treatment of Bronchitis, Cough and Allergy been made to develop and enhance the stability of two combined drugs Ambroxol Hydrochlori Cetirizine Hydrochloride Hydrochloride officially in Indian Pharmacopoeia (IP) is chemically Trans-4-[(2-amino amino]-cyclohexanol Hydrochloride yellowish crystalline powder water, methanol and practically insol methylene chloride [1, mucopolysaccharides directly and by liberating lysosomal enzymes which breakdown the tenacious sputum. It is particularly useful if mucus plugs are present. The breakdown of acid mucopolysaccharide fibers makes the sputum thi and less viscous, therefore coughing [3]. It acts as a bronchosecretolytic and expectorant drug. It stimulates the transportation of the viscous secretions in the respiratory organs and reduces the accumulation of the Ambroxol Hydrochloride (AMB) is semisynthetic derivative of vasicine obtained from Indian shrub Adhatoda vasica. It is a metabolic product of bromhexine, used in a variety of respiratory disorders including chronic bronchitis and treatment of cough [5]. Its molecular weight is 414.6 g/mole, dissociation constant (pK 8 The breakdown of acid mucopolysaccharide fibers makes the sputum thinner therefore easily removed by It acts as a bronchosecretolytic and expectorant drug. It stimulates the transportation of the viscous secretions in the respiratory organs and cumulation of the secretions [4]. Ambroxol Hydrochloride (AMB) is semisynthetic derivative of vasicine obtained from Indian shrub . It is a metabolic product of bromhexine, used in a variety of respiratory disorders including chronic bronchitis and is also used in the Its molecular weight is 414.6 dissociation constant (pKa) 8.2 and half life is melting point is 235°C to 240°C [3,6]. Cetirizine is a selective, second-generation histamine H1 receptor antagonist [7,8]. Chemically cetirizine hydrochloride, 2-(2-(4-((4chlorophenyl)(phenyl)methyl)piperazin-1yl)ethoxy)acetic acid hydrochloride [8]. It is white or almost white powder, freely soluble in water, practically insoluble in acetone and in methylene chloride [9,10]. Cetirizine hostile to H1 specificity seems exceptional in being without activity on receptors other than H1 receptor, most intense antihistamine in the skin and the lung [11]. It has long duration of activity and low potential for interaction with drugs metabolised by the hepatic cytochrome P450 system, inhibiting histamine-induced wheal and flare responses and also possessing inhibitory effects on eosinophil chemotaxis [12][13]. A dose of cetirizine 10 mg every day adequately controls or keeps the indications of unfavorably susceptible diseases [14]. CTZ is less extensively metabolised than different antihistamines and roughly 60% of a managed measurement is discharged unaltered in 24 hr [15]. This drug widely used for symptomatic relief in urticaria, allergic rhinitis, chronic urticaria, and pollen-induced asthma [10]. Cetirizine has the upsides of noncardiotoxicity as compare to other H1 antihistamines [16]. The concept of fast dissolving/disintegrating tablets emerged from the desire to provide patients with more conventional means of taking their medication when drinking water is not available and in certain cases such as motion sickness, sudden episodes of allergic attacks, or coughing. Particularly these types of difficulty are faced by pediatric and geriatric patients. Recent developments in technology have presented viable dosage alternatives for pediatric, geriatric, bedridden, nauseous or noncompliant patients.

Selection of Excipients and Optimization of Their Concentration
In the development of stable fast disintegrating tablets, the most important parameters that needs to be optimized are disintegration time and stability study. The tablets were prepared using different excipients (binders and superdisintegrants) and then evaluated for various parameters like friability, hardness and disintegration time. Among them best formulation was selected for further study like dissolution test and stability study.

Optimization of Superdisintegrant Sodium Starch Glycolate
Total six batches formulation (F1-F6) were prepared, shown in Table I. Tablets were prepared by the technique of direct compression. Required quantity of each ingredient was taken for each specified formulation. The superdisintegrant, Sodium Starch Glycolate (1%, 2%, 4%, 6%, 8%, and 10% concentration) was used to develop the tablets. All the ingredients were passed through mesh size #60. All the ingredients were cogrind in a pestle motor and finally talc and Sodium Stearyl Fumarate were added and mixed for 5 minutes. The mixed blend of excipients was compressed into tablets using tablet compression machine (Madhur Industries, India).  [17] Post compression Parameters

Hardness test
The hardness of three randomly selected tablets from each formulation was determined using Monsanto hardness tester by placing each tablet diagonally between the two plungers and applying pressure until the tablet broke down into two parts completely and the reading on the scale was noted down in Kg/cm The hardness of the formulations was shown in Table  II.

Thickness
The thickness of three randomly selected each formulation was determined in mm using a Vernier caliper. The thickness of the formulations was shown in Table II.

Friability test
Friability was determined by weighing 20 tablets after dusting. Placing 20 tablets in the friabilator and rotating the plastic cylinder vertically at 25 rpm for 4 min. After dusting, the total remaining weight of the tablets was recorded and the percent friability was calculated as: Original ] × 100. The friability test results of the formulations were shown in Table II.

Uniformity of weight
The weight (mg) of each of 20 individual tablets, selected randomly from each formulation was determined by dusting each tablet off and placing it in an electronic balance. The weight data from the tablets were analyzed for sample mean and percent deviation. The weight variation test formulations were shown in Table II.

DRUG CONTENT UNIFORMITY [9
Each batches ten tablets were powdered and the blend equivalent to 30 mg of Ambroxol Hydrochloride 5 mg of cetirizine hydrochloride was weighed and dissolved in suitable quantity of 6.8 pH phosphate buffer. The solution was sonicated, filtered, and suitably diluted and the drug content was determined

OF PREPARED
The hardness of three randomly selected tablets from each formulation was determined using Monsanto hardness tester by placing each tablet diagonally two plungers and applying pressure until the tablet broke down into two parts completely and the reading on the scale was noted down in Kg/cm 2 .
shown in Table   The thickness of three randomly selected tablets from n was determined in mm using a hickness of the formulations was was determined by weighing 20 tablets after dusting. Placing 20 tablets in the friabilator and rotating the plastic cylinder vertically at 25 rpm for 4 min. After dusting, the total remaining weight of the tablets was recorded and the percent friability was Original) / Weight results of the The weight (mg) of each of 20 individual tablets, selected randomly from each formulation was determined by dusting each tablet off and placing it in balance. The weight data from the tablets were analyzed for sample mean and percent weight variation test results of the 9, 17] en tablets were powdered and the blend Ambroxol Hydrochloride and mg of cetirizine hydrochloride was weighed and dissolved in suitable quantity of 6.8 pH phosphate buffer. The solution was sonicated, filtered, and and the drug content was determined from simultaneous equation method by using Double 1800 Shimadzu) at nm and 230 nm wavelengths corresponding to and cetirizine hydrochloride, respectively. Each sample was analyzed in triplicate, and mean±SD was calculated and the resulted data were shown in Table II.
Surface pH Study: The tablets (n=3) were made in contact with 1 ml of distilled water and allowed to swell for 2 hr at room temperature. The pH was measured by bringing the pH meter electrode ( 962-p) in contact with the surface of the tablet and allowing it to equilibrate for 1 studied results of the formulations Table II.

Disintegration study
The disintegration test is conducted using the disintegration test apparatus ( disintegration test apparatus). The vessel is provided with a thermostat to regulate the temperature of the fluid medium to the desired temperature. The test was carried out on 6 tablets of each batches formulation using disintegration media, hydrochloric acid pH 1.5 at temperature 37.5ºC ± 2ºC. The time in seconds is taken for complete disintegration of the tablet, so that no palatable mass remaining in the apparatus. study was performed in triplicate and mean±SD was calculated and the results of the formulations shown in Table II.
In vitro dissolution study [17 In vitro drug release of the prepared mouth dissolving tablets was carried out using USP apparatus (paddle type). The dissolution medium, 900ml saline phosphate buffer medium of pH 6 placed into the dissolution flask maintaining the temperature of 37 ± 0.5 °C and 50 rpm. One tablet was placed in each bucket of The apparatus was allowed to run for 5 Samples measuring 5 ml were withdrawn after every 10, 20, 30, 40, and 50 minutes sampling samples were filtered by 0.45µm syringe filter. The fresh dissolution every time with the same quantity of the withdrawn sample. Collected samples were the drug content was determined from simultaneous equation method by using Double Beam UV Spectrophotometer (UV-1800 Shimadzu) at 244 and 230 nm wavelengths corresponding to Hydrochloride and cetirizine hydrochloride respectively. Each sample was analyzed in triplicate.
Same procedure was carried out in buffer medium pH 7.4 and the resulted data were summarized in Table III, Table IV and Figure  Figure 2. Page: 1898 , and mean±SD was calculated shown in Table II.
The tablets (n=3) were made in ml of distilled water and allowed to at room temperature. The pH was asured by bringing the pH meter electrode (Max ) in contact with the surface of the tablet and ing it to equilibrate for 1 min. The surface pH results of the formulations were shown in test is conducted using the disintegration test apparatus (Electro lab disintegration test apparatus). The vessel is provided with a thermostat to regulate the temperature of the fluid medium to the desired temperature. The test was of each batches formulation using disintegration media, hydrochloric acid pH 1.5 at temperature 37.5ºC ± 2ºC. The time in seconds is taken for complete disintegration of the tablet, so that no palatable mass remaining in the apparatus. The ormed in triplicate and mean±SD was of the formulations were

17]
drug release of the prepared mouth dissolving lets was carried out using USP-type II dissolution apparatus (paddle type). The dissolution medium, e buffer medium of pH 6.8, was placed into the dissolution flask maintaining the temperature of 37 ± 0.5 °C and 50 rpm. One tablet was placed in each bucket of dissolution apparatus.
paratus was allowed to run for 50 minutes. ml were withdrawn after every 10, 20, 30, 40, and 50 minutes using a pipette. During sampling samples were filtered by 0.45µm syringe filter. The fresh dissolution medium was replaced every time with the same quantity of the withdrawn sample. Collected samples were suitably diluted and the drug content was determined from simultaneous equation method by using Double Beam UV 1800 Shimadzu) at 244 nm nm wavelengths corresponding to Ambroxol and cetirizine hydrochloride . Each sample was analyzed in triplicate.
Same procedure was carried out in saline phosphate and the resulted data were Samples were taken at monthly intervals and performed to determine the percentage of drug degraded at a temperature of 40°±2 C and at 75% Relative Humidity. The resulted data were shown in Table V.

Result and conclusion:
The disintegration time of F6 formulation was minimum than the other formulations and it was found to be 62.8 ± 2.39 seconds. And the dissolution studies results of F6 formulation in saline phosphate buffer pH 6.8 dissolution medium, cumulative % drug released of CET was found to be 100.4% at 20 min. and AMB 72% at 20 minutes. Also in saline phosphate buffer pH 7.4 dissolution medium, cumulative % drug released of CET was found to be 100.1% at 20 min. and AMB 81% at 20 min. The result of the stability study of F6 formulation indicated that there were not much more differences in hardness, disintegration time, drug content uniformity, and friability before and after the stability study (40±2° C at 75 % RH). So from the above studied results revealed that F6 formulation of two combine drugs cetirizine hydrochloride and Ambroxol hydrochloride tablets were stable and the drugs released were fast than the others formulations.