Formulation and Evaluation of Aspirin Tablets by Using Different Lubricants in Combination for better Kinetic Drug Release Study by PCP

 

Pawan Singh*, Prevesh Kumar, Dr. Neelkant Prasad

Asst. Professor, IFTM University Moradabad-244001

 

ABSTRACT:

Aspirin tablet is prepared by wet granulation method. Aspirin belonging to the class of NSAID having analgesic, antipyretic, anti-inflammatory and antiplatelet activity at systematic standard doses. In this Lubricants in combination leads to better drug release kinetic. The Prepared Tablet is Evaluated In terms of bulk density, tapped density, the angle of repose, Carr’s Index and, hardness test, weight variation test, friability test and in vitro study. The result associated with optimized batch is good satisfactory and having better drug release kinetic. The in-vitro dissolution studies we got result our formulation follow Zero Order Kinetics with the effect of lubricants using in combination for better kinetic drug release.

 

 

 

INTRODUCTION:

Aspirin also has an antiplatelet effect by inhibiting the creation of thromboxane, which binds platelet molecules together to generate a patch over damaged walls of blood vessels. Aspirin is used for long-term, at low doses, to prevent heart attacks. Aspirin tablets are obtained by wet Compression Method. The particles to be compressed consist of one or more medicaments, with or without excipients substance such as diluents, binders, and disintegration agents, lubricant, glidants and substances capable of modifying the behavior of the medicaments in the digestive tracts. Such substances must be innocuous and therapeutically inert in the quantities present.

 

Many strategies are available for the design and development of modified-release drug delivery formulations. ^[1]

 

Conventional oral dosage forms often produce fluctuations of drug plasma level that either exceeds safe therapeutic level or quickly fall below the minimum effective level; this effect is usually totally dependent on the agent’s biologic half-life, the frequency of administration, and especially the releaserate^[2]. For this purpose, aspirin which is analgesic and antipyretic was selected as a model drug. They are intended for oral administration. Some tablets are swallowed whole or after being chewed, some are dissolved or dispersion in water before administration and some are retained in the mouth where the active ingredient is liberated. Preparation intended for administration by other routes, for example, in the form of implants and passerines may also be presented in the form of tablets but because they may require special formulations, methods of manufacture or from of presentation appropriate to the use they may not comply with all the requirement of this monograph. Because of their composition, a method of manufacture or intended use, tablets present variety of characteristics and consequently there are several categories of tablets. Useless otherwise stated in the individual monograph, tablets are uncoated. Where the coating is permitted the monograph directs coating the statement reads “The tablets are coated “Unless otherwise directed, tablets may be coated in one of the different ways. Tablets are the most widely used unit solid dosage form of the drug (s) administered by oral route. These are administered into the body to produce systemic effects of the drug to cure, prevent or suppress the disease condition. More than 90% of the marketed drugs are formulated in the form of tablet dosage form as they produce several advantages in comparison to other dosage forms such as lack of physical and chemical stability of the drug in the form of liquids, easy to handle, self-medication can be possible etc. There are different classes of tablets available in the market, in that uncoated and coated tablets are one class. Some of the drugs may be damaged in gastric environment and some may irritate the gastric mucosa. Drugs that produce this effect are NSAIDS, potent antibiotics like erythromycin, azithromycin etc. For these type of drugs, layers of coating solution are applied to form a thick coat around the tablet which may prevent the drug exposure to the acidic environment and moreover prevents gastric irritation.

 

Binder:

Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dose tablets. Binders are usually:

 

Observation Table: List of Binder used in the Tablet Formulation

S.NO.	BINDER	EXAMPLE
1	Saccharides	Sucrose, lactose
2	Polysaccharides	Starches, cellulose as microcrystalline cellulosehydroxypropyl cellulose
3	Sugar alcohols	Xylitol, sorbitol or maltitol
3	Protein:	gelatin
5	Synthetic polymers:	Polyvinylpyrrolidone (PVP), polyethylene glycol (PEG).
6	Solution binders	Polyvinylpyrrolidone, starch, sucrose and polyethylene glycol, water or alcohol
7	Dry binders	Methylcellulose, Polyvinylpyrrolidone, and Polyethylene glycol.

 

LUBRICANTS:

These are preventing ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low resistance between the solid and die wall. lubricants in tablets or hard gelatin capsules. Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics.

 

Table 2: Lubricants Used in the Tablet Formulation

S.NO.	LUBRICANTS	EXAMPLE
1	Minerals	talc or silica,
2	fats	stearin, magnesium tearate or stearic acid

 

MATERIALS AND METHODS:

Materials:

Aspirin, HPMC, PVP, Sodium Stearate, Talc were procured from Research Lab, IFTM University, Moradabad. All the chemicals and reagents were of analytical grade.

 

CALIBRATION CURVE:

A standard calibration curve of aspirin was constructed in phosphate buffer (pH 7.2) and assayed spectrophoto metrically at 265 nm. the data obtained are given below:

 

Concentration X (µg/ml)	Absorbance Y (nm)
0	0
0.5	0.122
1	0.241
1.5	0.331
2	0.432
2.5	0.542

 

Equation for the standard curve: Conc. = 4.68

Abs. + -0.051                     R = 0.9989

 

Method of Preparationof Aspirin tablet:

Four different batches of the tablet were prepared using wet granulation technique. The composition of a tablet per batch is given in Table 1.

 

The calculated amount which was required to prepare 400 mg aspirin tablets, containing 250 mg drug, HPMC polymer, and PVP as abinderwere mixed uniformly^[3].

 

An enough granulating agent (water) was added slowly to prepare wet mass. Granules were prepared by sieving method using a20# sieve. ^[4]

 

Further, granules were dried at 35-45ºC for six hours. The dried granules were stored in desiccators until compression of tablets. Prior to compression, the dried granules were subjected to study and evaluated for their flow characteristics. ^[5]

 

The required amounts of granules were weighed and compressed using automaticallyoperated tablet punching machine having 12mm flat faced punch diameter. and during the tablet preparation to maintain the low resistance between the solid and die wall, lubricants added  in granules. Lubricant combinations are agents added in small quantities to the tablet during the tablet preparation.

 

The compressed tablets of each batch were stored in airtight container at room temperature for further study. ^[6]

 

Table 1: Formula Used to Prepare Tablet.

S. No	Ingredients (mg)	F1	F2
1	Aspirin	250	250
2	HPMC	50	50
3	Microcrystalline cellulose	70	70
4	Polyvinyl Pyrrolidone	Q. S.	Q.S.
5	Sodium Stearate+ Talc	1+5	0.5+10

 

Evaluation of granules:

Granules were evaluated for all pre-compression parameters like angle of repose, bulk density, tapped density, bulkiness, Hauser's ratio and compressibility index. The evaluation was done using all the methods as per specified in pharmacopeias^[7].

 

Table 2: Pre-Compression Properties of Granules.

 

Evaluation of Tablets:

Weight variation:  

Tablets were evaluated for weight variation as per USP XXIV monograph using digital electronic balance. Twenty tablets of each batch were used to evaluate weight variation among tablets and mean and the standard deviation was calculated^[8].

 

Friability:

Friability of a tablet can determine in the laboratory by Roche Friabilator. This consists of a plastic chamber that revolves at 25 rpm. Tablets were used to evaluate friability as per USP XXIV monograph. Friability testing was done by Roche Friabilator with readings in triplicate^[9].

 

Hardness:

Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shakes during handling in the manufacture, packaging, and shipping. Hardness generally measures the tablet crushing strength. The hardness of tablets was determined using Pfizer hardness tester. ^[10].

 

Thickness:

The thickness of the sustained release tablets was determined using Vernier caliper. and the results were expressed as mean values of 10 determinations, with standard deviations^[11].

 

Disintegration Test (U.S.P.):

The U.S.P. device to test disintegration consists of 6 glass tubes that are 3inch long; open at the top and 10 mesh screens at the bottom end. During the disintegration test, one tablet is placed in each tube and the basket rack is positioned in a 1-L beaker of either water, simulated gastric fluid or simulated intestinal fluid at 37 ± 2 °C such that the tablet remains 2.5 cm below the surface of liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in their downward movement. Move the basket containing the tablets up and down through 5-6 cm at a frequency of 28 to 32 cycles per minute.

 

Drug content:

The tablets were powdered, and 250 mg equivalent weight of aspirin in tablet powder was accurately weighed and transferred to a 100-ml volumetric flask. Initially, 10 ml of phosphate buffer (pH 7.2) was added and shaken for 10 min. ^[12]Thereafter, the volume was made up to 100 ml with buffer. Subsequently, the solution in the volumetric flask was filtered, and 1 ml of the filtrate was diluted and analyzed at 265 nm using UV-visible spectrophotometer (Shimadzu UV-1800, Japan). The drug content of each sample was estimated from their previously prepared standard curve^[13].

 

Table 3: Result-Evaluation parameters of tablets.

 

Kinetics of Drug Release:

Kinetics drug release was studied, in 900 ml phosphate buffer pH 7.2, maintained at 37±2°C for 6 h, at 100 rpm. 5ml of the sample was withdrawn after a specified time interval and was replaced by an equal volume of fresh dissolution medium.20 Collected samples were analyzed spectrophotometrically at a measured wavelength of 265 nm, and cumulative percent drug release was calculated^[10-11]. The test was performed in triplicate to assure significance of results. Drug release profile was studied using percentage drug release Vs time (h) plot.^[14]the kinetic study was done F2batch,Various models such as Zero order kinetics (cumulative percentage amount of drug release versus time), First order kinetics (log cumulative percentage of drug remaining to release versus time), Higuchi (fraction of drug release, Mt/Mi, versus square root of time) and Korsermeyer-Peppas (log fraction of drug released, were applied to assess the kinetics of drug release from prepared tablets. Most suited model for drug release was predicted based on regression coefficient i.e. nearer the value of regression coefficient towards 1, greater the suitability of best-fitted release mechanism.^[15]

 

 

CONCLUSION:

The Tablet of the Aspirin is Prepared by the Direct Compression Process. the maximum drug release in four hours was found to be in batch F1, which is far less than the release of drug in reference tablet All these values have been tabulated below in Table 3. The in-vitrorelease profile of the drug from the tablets was major governing criteria to decide the commercially used binder (starch as in reference batch) is a good binding agent. The release profile for the drug was taken for a period of four hours which can best be depicted by graph between percentage drug release and time Batch F2contain.

 

DISCUSSION:

Physical properties of granules: Parameters studied were the angle of repose, carr’s index, Hauser's ratio, bulk density, tapped density, and bulkiness. Lesser bulkiness showed the ease of compaction into tablet dosage form over conventional dosage forms containing binders such as starch. As per the results of physical characterization batch from F1 and F2. especially the

 

reference batch, do not show much difference in micromeritics studies and granule flow property. By adding the lubricant in the combination.

 

Kinetic profile of drug release:

By the using the lubricant in the combination in this formulation. F2 Formulation was found to be best under the all pharmaceutical parameters and our F2 formulation follows Zero Order Kinetics Mechanism.

 

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10.   Taday PF. Applications of terahertz spectroscopy to pharmaceutical sciences. Philosophical transactions Series A, Mathematical, physical, and engineering sciences. 2004;362(1815):351-63; Discussion 63-4.

11.   Taylor M, Elhissi AM. Predicting the physical properties of tablets from ATR-FTIR spectra using partial least squares regression. Pharmaceutical Development and Technology. 2011;16(2):110-7.

12.   Gamal W, Fahmy RH, Mohamed MI. Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits. Drug Development and Industrial Pharmacy. 2017:1-29.

13.   Tawfeek HM, Faisal W, Soliman GM. Enalapril maleate orally disintegrating tablets: Tableting and in vivo evaluation in hypertensive rats. Pharmaceutical Development and Technology. 2017:1-25.

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Accepted on 20.07.2017        © RJPT All right reserved