Formulation and Evaluation of Acacia Catechin (Heartwood) Tablet an Experimental Study

Tablets are solid preparations each containing a single dose of one or more active substances and usually obtained by compressing uniform volumes of particles. Tablets are intended for oral administration. The compressed tablet is refers to standard uncoated tablet made by compression and employing of the basic method or manufacture: wet granulation, double compaction or direct compression. Tablets are usually intended provide rapid disintegration and drug release Most tablets containing drug intended to exert a local effect in the GIT of this type. [1]Obesity is chronic metabolic disorders which occurs as a result by increase the energy intake and decrease the exercise expenditure. Obesity can be defined as excess accumulation of fat rather than normal fat in the body. It is worldwide health problem. Obesity is a major risk for developing various disease such as cardiovascular disease, diabetes mellitus, cancer, high blood pressure, dyslipidaemia. Person is considered obese when body weight is more than 20%. If the BMI between 25 and 29.9 is considered as over weight. If your BMI is 30 or over you are considered obese person. BMI is defined as a person’s weight in kilograms (kg) divided If by height in meters squared (kg/m2) .[2]A herbal drug of Acacia catechin is mainly used as anti-obesity drug and till today available in marketed in churna forms therefore Main purpose is to convert in  tablet dosage forms. Now a days herbal drug are more preferred because it has lesser side effect as compared to synthetic drug. The oral route of drug administration is the most popular and successfully used for conventional delivery of drugs. It offers the advantages of convenience, ease of administration, greater flexibility in dosage form design, ease of production and low cost. [3]Acacia Catechu is to be one of the widely growing plants found at an altitude of 1200m in the forest area including the sub-Himalayan tract in India as well as in Pakistan, Nepal, Bhutan, Thailand, and China. The heartwood of this plant is to give a medicinally potent product is known  as  Katha  having  a  wide  range  of therapeutic potential The prime phytoconstituents of the heartwood are catechin or epicatechin/catechin exists in this plant performs an important function such as antioxidant, anti-inflammatory, antimicrobial & anticancer potential.[4] Disadvantages of Churna is Inconsistent dosing: Churna can be led to inconsistence dosing, as it can difficult to accurately measure the dosing Limited bio availability: as the powder may not dissolve or absorb well. Poor flowability. Patient non-compliance: churna can be unpleasant to take. Messy and difficult to handle. [5]

MATERIALS AND METHODOLOGY:

The Herbal pharmaceutical ingredients, A. Catechin(Heartwood) was purchased from KLE Ayurvedic Pharmacy, Belagavi. Other Chemical-Lactose, Sodium Starch Glycolate and Talc were acquired from Burgoyne Burblidges & Co. ,India. All the chemicals and solvents used were of analytical grade.

Preparation of Standard Calibration Curve of Pure Acacia Catechin:[6]

Principle: When examined in the range of 200 to 400 nm in phosphate buffer pH 6.8 solution, Acacia catechin show an absorption maximum peak at 274 nm.

Procedure: Preparation of Stock Solution:

A standard curve was prepared by dissolving 100mg of Acacia Catechin in phosphate buffer(pH 6.8 )an make up to a volume of 100 mL. It was further diluted to get the solution in concentration range of 0.25 µg/mL. The absorbance value were recorded at 274 nm.

Preparation of Working Standard Solution:

Further from second stock(SS-II), aliquots of 0.5, 1, 1.5, 2, 2.5mL were pipette 10 ml volumetric flask. The volume was made up with phosphate buffer(pH6.8) to get the final concentration of  2,  4, 6, 8, 10µg/mL respectively. The absorbance of each concentration was measured at 274nm.

Preparation of Acacia Catechin Tablets:[7]

Accurately weigh specified quantity of Acacia Catechin (heart wood) and mix properly Add required quantity of diluents and super disintegrating agent and then glidant mix the mixture well for 10 min Lubricants are added and mixed for 10 mins. The powder is compressed into tablet in 10 mm by using tablet 10 stationary Rotary punching machine.

Table 1:Master formula for the preparation of Acacia Catechin tablets by Direct Compression Method

Table 2:Batch formula for the preparation of Acacia Catechin tablets by Direct Compression Method

Evaluation  test:

Organoleptic Properties: Preliminary examination of the organoleptic properties are evaluated for all the tablets: Color, surface.[8]

Tablet thickness: Tablet thickness is important for tablet packaging; very thick tablet affects packaging either in blisters or in plastic containers. Tablet thickness is determined by the diameter of die, the amount of fill permitted to enter die and force, or pressure applied during compression. The thickness should be controlled with in ±5% variation of standard value.[9] The diameter and thickness of the 10 tablets from each batch was measured using the Vernier caliper.[10]

Hardness test: The tablet should show sufficient mechanical strength withstand fracture and erosion during manufacturing and handling. Hardness test and friability test are used to check mechanical strength.[11]The crushing strength of the tablets was determined using the Monsanto hardness tester. Five tablets from each batch were randomly selected and tested and the average calculated. It is expressed in kg/cm2.[12]

Friability: 10 tablets were taken randomly and placed on a sieve. Loose dust was removed with the aid of air pressure or a soft brush. Tablet samples were weighed accurately and placed in Fibrillatory. After the given number of rotations (100 rotations/4 min) loose dust was removed from the tablets as before. Finally, tablets were weighed. The loss in weight indicates the ability of the tablets to withstand this type of wear. The percent friability was determined by using following formula.[13]

% Friability = (Initial weight- Final weight) X 100

Initial weight

Weight Variation: Twenty tablets were randomly selected from each batch and individually weighed. The average weight and standard deviation of 20 tablets was calculated. The batch passes the test for weight variation test if not more than two of the individual tablet weights deviate from the average weight by more than the percentage shown in table and none deviate by more than twice the percentage shown in table.[14]

Table 3: Weight variation as per IP

Disintegration test: The disintegration time test was carried out according to USP standards using six tablets from each formula were added into the basket of disintegration apparatus and temperature was set at 37 ± 2°C and time required for complete disintegration of the six tablets was recorded.[15]

In-vitro Dissolution studies: The dissolution study of all tablets conducted using dissolution testing USP apparatus II (paddle method) using 900 ml Acid solution (pH 1.2) at 37 ± 0.5ºC and at 50 rpm, aliquots of dissolution medium was withdrawn at an interval of 10 minutes and filtered through 0.45 µm filter. The equal volume withdrawn from the dissolution medium was replaced. The collected sample is suitably diluted and assayed against suitable blank using UV-visible spectrophotometer at 27 nm and the drug release was compared with the pure drug.[16]

Details of Dissolution test:

• Dissolution test apparatus : USP Type II Apparatus
• Speed  :  50rpm
• Stirrer  :   Paddle type
• Volume of medium  :  900 ml
• Volume withdrawal  :  10ml
• Medium used  : Acidic solution(pH 1.2) & buffer solution(6.8)     
• Temperature  :  37 ± 0.59 C

Stability studies of the optimized formulation:

Stability of a pharmaceutical preparation can be defined as “the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic and toxicological specification throughout its shelf life”

ICH specification for stability

• Accelerated testing 400C ± 20C / 75% RH ± 5% RH for 6 months.
• Intermediate testing 300C ± 20C / 65% ± 5% RH for 12 months.
• Long term testing 250C ± 20C / 60% RH ± 5% RH for 12 months.

Procedure: Stability studies for the present work were carried out at 25? C ± 2? C / 60% RH and 40? C ± 2? C / 75 % RH for the optimized formulation (F2) for one month. For stability study, the tablets were sealed in aluminum packaging coated inside with polyethylene and evaluated for their physical appearance and drug content at specified intervals of time. These sample containers were placed in a stability chamber.

Evaluation of samples: The samples were analyzed for the following parameters:

Physical evaluation:

• Appearance: The samples were checked for any change in color every week.
• Hardness: The samples were tested for hardness every week.

Chemical evaluation:

• Drug content: The samples were checked for drug content.
• Disintegration test: The sample was evaluated for disintegration study every week.
• Drug release: The samples were subjected to drug release studies.[17]

RESULT AND DISCUSSION

Table 4: Pre-Compression studies of formulated powder

Bulk density of F1 and F2 ranged between 0.4 to 0.5 g/cm3 and tapped density was in the range of 0.5 to 0.6 g/cm3 for F1 and F2 formulation. Good flow of property is indicated by the closeness of its Bulk density with Tapped density F1 and F2 having good flow property. Both two formulations show the value of angle of repose ranging from 30 to 35 Which is indicating good flow properties. Carr’s index of the F1 formulation was found to be 21% indicate passable flowability and compressibility properties, Carr’s index of the F2 formulation was found to be 13% indicate good flowability and compressibility properties. The Hausner’s ratio of F1 formulation was found to be 1.26 indicates passable flow property and moderate degree of powder flowability. The Hausner’s ratio of F2 formulation was found to be 1.15 indicates good flow property and high degree of powder flowability.

Graph 1: Bulk density & Tapped Density

Graph 2: Carr’s  index

Graph 3: Hauser’s ratio

Graph 4 :Friability test

POST COMPRESSION STUDY

Table 5: Post Compression Parameters of Acacia Catechin tablets

Figure 1: F1 Tablets                                                                    Figure 2: F2 Tablets

All the tablets were prepared by direct compression method and were found to be brown round, smooth textured/shiny surface. The thickness of F1 and F2 formulation was in the range. F1 and F2 formulation showed average hardness in the range of 4 - 4.2 kg/cm The average weight of the tablets of F1 and F2 formulation was 250 – 253 mg. The friability test results of F1 and F2 were within the limit less than 1%

Figure 3:Tablet punching machine

Figure 4: Friability test

Figure 5: Diameter of tablet

Figure 6: Thickness of tablet

 Disintegration test:

Table 6: Disintegration time test

Graph 5: Disintegration time test

Figure 7: Disintegration apparatus

The disintegration of F1 and F2 was found to be 33 second and 16 second respectively. It was observed that addition of sodium starch glycolate as super disintegration time was reduced second to 16 second.

Standard calibration curve of Acacia Catechin:

Table no. 06: Standard calibration curve of Acacia Catechin

Graph 5 :Standard calibration curve of Acacia Catechin

In vitro dissolution studies:

Table 7: In vitro dissolution study of F1 formulation (1.2pH)

Table 8: In vitro dissolution study of F2

Graph 6: In-vitro drug release profile (% CDR v/s Time) in 1.2 pH

Table no: 09 In vitro dissolution study of F1 formulation (6.8pH)

Table no: 10 In vitro dissolution study of F2 formulation (6.8Ph)

Graph 7: In -vitro drug release profile (% CDR v/s Time) in 6.8 pH

The rate of dissolution affects how quickly and how much a drug is absorbed, as well as how well it works therapeutically. The type and concentration of the binder, hardness, surface area, diffusion distance, solubility of the medication, manufacturing technique (wet granulation, dry granulation, or direct compression), and diluents can all have an impact on the dissolution test.

Graph 8: % CDR in 60min (6.8 pH)

Graph 9: % CDR in 60min (1.2 pH)

Stability Studies:

Table 11 :Short -term stability studies