Development and Characterization of Medicated Chewing Gum Containing Ambroxol HCl for Treatment of Bronchitis

Dr. S. J. Daharwal*, Rajendra K. Jangade, Veena Devi Thakur, Shikha Srivastava and Bhanu Pratap Sahu

University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.) India

ABSTRACT:

Patient convenience and patient compliance-oriented research in the field of drug delivery has resulted in bringing out potential innovative drug delivery options. Out of which Medicated chewing gum delivery system is convenient, easy to administer - anywhere, anytime - and is pleasantly taste making it patient acceptable. It offers a wide range of advantages that make it an excellent alternative. Various characterization parameters like hardness, drug content, stability and drug release were studied and best formulation was chosen.

KEYWORDS: Chewing gum, stability, innovative

1. INTRODUCTION:

Oral route is most preferred route amongst the patient and clinicians due to various advantages like ease of administration and self-medication.¹Drug administration by oral route is the most common method for systemic effects. Out of which, medicated chewing gum (MCG) offers a highly convenient patient-compliant way of dosing medications, not only for special population groups with swallowing difficulties such as children and the elderly, but also for the general population, including the younggeneration.²Medicated chewing gum is considered as vehicle or drug delivery system to administer active principle and nutrition that can improve health and creates additional patient benefits and add new competitive advantage for a drug and thus increase revenue. Chewing gum permits more rapid therapeutic action amongst per oral dosage form. Intra oral drug delivery over comes hepatic first pass metabolism and promotes rapid systemic delivery with improved bioavailability. Xerostomia, Allergy, Motion sickness, Acidity, Diabetes, Anxiety, Cold and Cough etc. are indications for which chewing gum is a means of drug delivery.

Chewing gum formulation basically consists of natural or synthetic gum base, active ingredient and several non-masticatory ingredients such as softeners, sweeteners, bulking sweeteners, fillers, coloring and flavoring agents. Now a day the gum base used are mostly of synthetic origin³.

Bronchitis is the inflammation of the mucus membrane of the bronchi, the airway that carry airflow from the trachea into the lungs. Bronchitis can be divided in to two category acute and chronic bronchitis. Acute bronchitis is characterized by the development of cough with or without the production of sputum, mucus that is expectorated (coughed up) from respiratory tract. Acute bronchitis often occurs during the course of an acute viral illness such

as the common cold or influenza. Acute bronchitis is most often caused by viruses that infect the epithelium of the bronchi, resulting in inflammation and increased secretion of mucus. Cough a common symptom of acute bronchitis; develop in an attempt to expel the excess mucus from the lung. Other common symptoms include sore throat, runny nose, nasal congestion, low grade fever and production of sputum.⁴

Ambroxol HCl i.e.N-desmethyl metabolite of bromhexine (N-(trans-p-hydroxycyclohexyl)-(2-amino3,5-dibromoben zyl) HCl Chewing gum containing antacids or mucolytics also presents advantages for patients. Productive cough, Acute and chronic inflammatory Disorder of upper and lower respiratory tract associated with viscid mucus including acute & chronic Bronchitis, Asthmatic bronchitis, bronchial asthma with thick expectoration, chronic pneumonia.⁵

2. MATERIAL AND METHOD:

2.1 Preparation of medicated chewing gum^6-8

A conventional method / melting method has been adopted for the preparation of MCG in which Synthetic gum base (polyvinyl acetate) was taken and melted at 75ºC and after 10 minute of stirring previously weighed quantity of plasticizer (glycerol) was added and then mixed thoroughly at the same temperature, the melting were carried out in a porcelain dish. Then resulting mixture was allowed to cool at temperature of 15-20ºC. Homogenous mixture of drug (Ambroxol HCl), sweetener and bulk sweetener (sorbitol, sucrose, mannitol) and filler (CaCO₃) was added with continuous stirring at constant temperature 40ºC so that to ensure even distribution of drug. Then flavor and color was added at the end of mixing. Then the mass was allow to cool at room temperature on steel plate ,the mass was rolled evenly and cut into the pieces of uniform size and weighed pieces are removed and wrapped properly.

Similarly nine batches were prepared by changing concentration of gum base (elastomer) and softener. (Table 1)

3. Characterization of Ambroxol HCl medicated chewing gum (MCG)^9,10

3.1. Morphological evaluation:

All chewing gum formulations were visually inspected for their physical properties like color.

3.2. Weight variation:

The weight variation test of the chewing gum was done as per the guidelines of USP 20.

Weight of ten chewing gums was taken from each formulation batch, then average weight is calculated, from that standard deviation is calculated.

3.3. Hardness:

Due to absence of any reported method, it was decided to use the Monsanto type hardness tester for determination of hardness of all MCG formulations.

3.4 Stability study:

The short term stability study of optimized formulation was performed as per ICH (International Conference on Harmonization) guidelines at 25ºC±5ºC and 65% ± 5% RH for three months and evaluated color and hardness.

3.5. Estimation of drug contents:

Chewing gums cannot be assayed unlike tablet by the conventional method that is by crushing the tablet and weighing an accurate amount of medicament and estimating its content. For estimation of the drug content in chewing gums and for the study of drug release process of medicated chewing gums a modified apparatus of Erweka’s DRT 6 Chewing apparatus has been designed which mimics the natural chewing actions.

The test cell was filled with 900 ml of Phosphate buffer 6.8. The chewing gum was placed and operated the instrument for 60 min at a chewing frequency of 60 strokes per minute, to ensure total release of the drug from the formulation in the 6.8 phosphate buffer. From the dissolution medium 10 ml was withdrawn and the absorbance of the resulting solution was read at 245 nm. The amount of drug present in the formulation was calculated using regression coefficient.

Table 1: Different components employed in formulation ofMCG

Sr.No.	Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9
1.	Ambroxol HCl(Drug)	30	30	30	30	30	30	30	30	30
2.	Gum base (PVA) (Elastomer)	400	400	400	600	600	600	800	800	800
3.	Glycerol (Softner)	60	120	180	60	120	180	60	120	180
4.	Sorbitol (Sweetner)	400	400	400	400	400	400	400	400	400
5.	Sucrose (Sweetner)	200	200	200	200	200	200	200	200	200
6.	Mannitol (Sweetner)	200	200	200	200	200	200	200	200	200
7.	Peppermint oil (Flavor)	50	50	50	50	50	50	50	50	50
8.	Color (Titanium dioxide)	40	40	40	40	40	40	40	40	40
9.	Calcium carbonate (Diluent)	620	560	500	420	360	300	220	160	100

3.6. To estimate in-vitro drug release of medicated chewing gum:

Procedure was followed as mentioned in section 3.5in which sample was used at different time intervals of 5, 10, 15, 20, 25 and 30 minutes. After each withdrawal of the sample, 10 ml of fresh 6.8 phosphate buffer was replaced to maintain the sink condition and no further dilution is required.

4. RESULT AND DISSCUSSION:

The medicated chewing gum appears to be compatible In terms of odor and color.

The hardness of formulations were found to be in the range of 2 to 7.5 kg. lowest hardness was found with F3 formulation and followed by F7 with higher hardness value. The order of hardness for different formulations was followed as:F7>F4>F1>F8>F5>F2>F9>F6>F3.

Weight variation of all the formulations were found satisfactory with in the range of 1.945±0.09501 to 1.975±0.07040.

The prepared formulation of Ambroxol hydrochloride chewing gum were analysed for the drug content and it was found to be in the range of 95.20 to 99.21% or 28.56 to 29.76 mg. F5 formulated chewing gum found with highest drug content of 29.76 mg Ambroxol hydrochloride and the formulation F7 with the lowest drug content of 28.56 mg Ambroxol hydrochloride.

Modified apparatus of Erweka’s DRT 6 chewing apparatus was used for the in-vitro drug release study Formulation F5 showed highest drug release of 98.74% and formulation F7 showed lowest drug release of 85.74% at the end of 30 minutes. . The in-vitro drug release of different formulations followed the order: F5>F3>F6> F2>F1>F4>F9>F8>F7. The percentage cumulative in vitro drug release of developed formulation were shown in Table:2 and represented in graph: 1,graph 2(A,B.C,D).

Table 2:%Cumulative drug release of developed formulations:

Time (min)	% Cumulative drug release
Time (min)	F1	F2	F3	F4	F5	F6	G7	F8	F9
05	28.20	26.43	26.74	27.10	29.76	27.33	24.86	25.86	26.20
10	46.00	44.76	45.30	44.86	48.42	45.09	42.76	44.66	45.43
15	60.66	60.42	60.83	59.76	63.52	60.29	57.09	58.39	60.19
20	73.09	73.52	74.73	74.09	76.98	74.29	68.85	70.85	73.32
25	84.75	84.75	87.63	83.75	88.64	86.85	78.41	81.28	83.98
30	93.51	95.31	97.50	92.35	98.74	96.75	85.74	88.18	91.74

5.CONCLUSION:

Medicated Chewing Gum of Ambroxol hydrochloride was successfully formulated by the conventional/melting method. Formulation F5 (30% PVA and 6% glycerol) showed highest drug release at the end of 30 minutes and formulation F7 showed lowest drug release at the end of 30 minutes. Formulation F5 showed good chewing like consistency Hardness of formulation F5 and F2 were almost similar but formulation F5 showed better drug release. So formulation F5 was selected as best optimized formulation. The formulation containing 20-30% of gum base (elastomer) and higher concentration of softener showed good drug release rate but did not show sufficient chewing gum like consistency. The formulation containing medium concentration of elastomer (30%) and medium concentration of softener (6%) are more promising in delivering drug at required rate and at the same time maintain the chewing like consistency. The formulation containing higher concentration of elastomer did not show good drug release rate. It is seen that as the concentration of the gum base is increased in the formulation, the drug release was decreased.

6. REFERENCES:

1. Parmar Vilcy William and ThosarMillind, A Comprehensive Review on Medicated Chewing Gum, International Journal of Research in Pharmaceutical and Biomedical Sciences, 2012:3(2): 894-906.

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Received on 10.07.2013

Modified on 02.08.2013

Accepted on 12.08.2013

Research Journal of Pharmaceutical Dosage Forms and Technology. 5(5): September-October, 2013, 295-299