The quantitative evaluation and assessment of tablets chemical, physical and bioavailability properties are important in the design of tablets and to monitor product quality. These properties are important since chemical breakdown or interactions between tablet components may alter the tablet's physical properties, and greatly affect the bioavailability of the tablet system.
There are various standards that have been given in the various pharmacopoeias regarding the quality of pharmaceutical tablets. These contain the diameter, size, shape, thickness, weight, hardness, disintegration and dissolution characters. The diameters and shape of the tablet depends on the die and punches selected for the compression of tablets. The quality control tests should be carried out on compressed tablets.
Tablet thickness is important for tablet packaging; thick tablets affect packaging either in blisters or plastic containers. The tablet thickness is determined by the diameter of the die, the amount of fill permitted to enter the die and the force or pressure applied during compression. Tablet thickness is reliable from batch to batch or within a batch only if the tablet granulation or powder blend is adequately consistent in particle size and particle size distribution, if the punch tooling is of consistent length, and if the tablet press is clean and in good working condition.
The thickness of individual tablets measured using micrometer, which permits accurate measurements and provides information of the variation between tablets. Tablet thickness should be controlled within a ±5% variation of a standard value. Any variation in thickness within a particular lot of tablets or between manufacturer's lots should not be obvious to the unaided eye for consumer acceptance of the product. In addition, thickness must be controlled to smooth the progress of packaging.
Micrometer (tablet thickness)
WEIGHT VARIATION TEST (USP, 2000)
The weight variation test is performed by taking 20 tablets from a batch. Then 20 tablets are weighed and the average weight was taken. Then each tablets were weighed individually. The percentage deviation can be determined by using the following formula:
Average weight - Individual weight
% Deviation = X 100
Average weight
Average Weight
Percent Difference
130 mg or less
10
More than 130 mg through 324 mg
7.5
More than 324 mg
5
HARDNESS TEST
The resistance of tablets to capping, abrasion or breakage under conditions of storage, transportation and handling before use depends on its hardness. Hardness, which is now more suitably called crushing strength determinations are made during tablet production and are used to determine the need for pressure adjustment on tablet machine. If the tablet is too hard, it may not disintegrate in the requisite period of time to meet the dissolution specifications; if it is too soft, it may not be able to withstand the handling during subsequent processing such as coating or packaging and shipping operations. The force required to break the tablet is measured in kilograms and a crushing strength of 4Kg is usually well thought-out to be the minimum for satisfactory tablets. Oral tablets normally have a hardness of 4 to 10kg ; but, hypodermic and chewable tablets are usually much softer ( 3 kg ) and some sustained release tablets are much harder (10 -20 kg ). Tablet hardness have been related with other tablet properties such as density and porosity. Hardness usually increases with normal storage of tablets and depends on the shape, chemical properties, binding agent and pressure applied during compression.
Pfzier hardness tester was used for measuring the hardness of the formulated Tamsulosin hydrochloride sublingual tablets. From each batch 3 tablets were taken at random and subjected to test. The mean of these 3 tablets were calculated.
FRIABILITY TEST (USP, 2000)
Friction and shock are the forces that most frequently cause tablets to chip, cap or break. The friability test is directly related to tablet hardness and is designed to assess the ability of the tablet to withstand abrasion in packaging, handling and shipping. It is frequently measured by the use of the Roche friabilator.
A number of tablets are weighed and placed in the apparatus where they are bare to rolling and repeated shocks as they fall 6 inches in each turn within the apparatus. After four minutes of this action or 100 revolutions, the tablets are weighed and the weight compared with the initial weight. The loss owing to abrasion is a measure of the tablet friability. The value is articulated as a percentage. A maximum weight loss of not more than 1% of the weight of the tablets being tested during the friability test is considered generally acceptable and any broken or smashed tablets are not picked up. Usually when capping occurs, friability values are not calculated. A thick tablet may have less affinity to cap whereas thin tablets of large diameter often show extensive capping, thus indicating that tablets with greater thickness have reduced internal stress.
TABLE 16:
Thickness, hardness and % friability of formulated tamsulosin hydrochloride sublingual tablets
Formulation code
Thickness
(mm)
Hardness
(kg/cm2)
Friability
(%)
F1 EC
2.328
1 kg/cm2
0.9472
F2 EC
2.4594
0.977
F3 EC
2.4144
1.188
F4 EC
2.1836
1.47
F5 EC
2.359
1.27
F1 P
2.398
0.678
F2 P
2.374
0.476
F3 P
2.3954
1.004
F4 P
2.4342
0.794
F5 P
2.4047
0.739
F1 CD
2.3421
0.7304
F2 CD
2.3647
0.808
F3 CD
2.3566
0.874
F4 CD
2.3826
0.808
F5 CD
2.3794
0.7702
F1 PVP
2.3605
1.10
F2 PVP
2.1605
0.8713
F3 PVP
2.385
0.884
F4 PVP
2.3475
0.74
F5 PVP
2.2982
0.873
F1 HPMC
2.356
0.899
F2 HPMC
2.3756
0.809
F3 HPMC
2.3942
0.997
F4 HPMC
2.4171
0.803
F5 HPMC
2.3941
0.469
B1
2.364
1.5kg/cm2
0.261
B2
2.4162
4kg/cm2
0.189
W1
2.367
0.468
W2
2.384
0.354
C1
2.365
0.784
C2
2.349
0.867
DRUG CONTENT ASSAY
The prepared sublingual tablets containing tamsulosin hydrochloride was tested for drug content assay. Five tablets has been weighed and crushed and weight equivalent to one tablet has been taken and dissolved in 3ml of methanol and total drug has been extracted in 7ml pH 6.8 phosphate buffer and the solution was filtered and filterate is used for estimating drug content assay by UV spectrophotometry at 280nm.
Table 17:
Drug content uniformity of tamsulosin hydrochloride sublingual tablets
Formulation code
Absorbance
(280 nm)
Amount of tamsulosin hydrochloride content per sublingual tablet
Amt(in mg)
Percentage purity(%)
F1 EC
0.26
0.4245
108
F2 EC
0.235
0.39
99.74
F3 EC
0.25
0.4093
104.3
F4 EC
0.242
0.3975
101.1
F5 EC
0.182
1.575
98.43
F1 P
0.246
0.3975
99.37
F2 P
0.25
0.4125
103.12
F3 P
0.226
0.372
93.0
F4 P
0.239
0.39
97.5
F5 P
0.205
1.725
107.81
F1 CD
0.23
0.375
93.75
F2 CD
0.242
0.405
101.25
F3 CD
0.218
0.3675
91.87
F4 CD
0.246
0.4125
103.12
F5 CD
0.190
1.6125
100.78
F1 PVP
0.232
0.3825
95.62
F2 PVP
0.25
0.4116
102.9
F3 PVP
0.241
0.405
101.25
F4 PVP
0.228
0.3825
95.62
F5 PVP
0.186
1.6125
100.78
F1 HPMC
0.239
0.39
97.5
F2 HPMC
0.226
0.375
93.75
F3 HPMC
0.248
0.3975
99.37
F4 HPMC
0.231
0.3825
95.62
F5 HPMC
0.198
1.635
102.18
B1
0.235
0.39
99.7
B2
0.242
0.405
101.25
C1
0.256
C2
0.2395
0.39
97.5
DRUG CONTENT UNIFORMITY OF VARIOUS TAMSULOSIN HYDROCHLORIDE SUBLINGUAL TABLETS
The prepared sublingual tablets containing tamsulosin hydrochloride was tested for drug content uniformity as per specifications of IP 1996. Five tablets were weighed individually , and the drug was extracted in phosphate buffer of pH 6.8. The drug content was determined as described. An accurately weighed amount of powdered tamsulosin hydrochloride tablet(100mg) was extracted with phosphate buffer pH 6.8 and the solution was filtered through 0.45-µ membrane. The absorbance was measured at 280nm after suitable dilution. The results were showed in table
Table 18:
Drug content assay of tamsulosin hydrochloride sublingual tablets:
Formulation code
Absorbance
(280 nm)
Amount of tamsulosin hydrochloride content per sublingual tablet
Amt(in mg)
Percentage purity
F1 EC
F2 EC
F3 EC
F4 EC
F5 EC
F1 P
F2 P
F3 P
F4 P
F5 P
F1 CD
F2 CD
F3 CD
F4 CD
F5 CD
F1 PVP
F2 PVP
F3 PVP
F4 PVP
F5 PVP
F1 HPMC
F2 HPMC
F3 HPMC
F4 HPMC
F5 HPMC
B1
B2
DISSOLUTION
In vitro release studies were performed using phosphate buffer solution (pH 6.8) and of 30ml volume at 37°C using a modified dissolution apparatus. The modified dissolution apparatus consisted of a 250-mL beaker as a receptor compartment and a glass rod attached with a grounded glass disk (2-cm diameter) as a donor tube. The back surface of the sublingual tablet was attached to the glass disk with instant adhesive (cynoacrylate adhesive). The donor tube was then dipped into the receptor compartment containing dissolution medium, which was maintained at 37°C ± 0. 2°C, and stirred at a constant speed using a magnetic bead. For each 5min interval 3ml of the sample was withdrawn from receptor compartment, filtered through a 0.2-μ filter, and then the amount of drug released was estimated by measuring the absorbance at 280 nm using a UV spectrophotometer. The dissolution medium of same volume (3 mL) prewarmed at 37°C ± 0.2°C was replaced to maintain its constant volume and sink condition. The cumulative amount of drug release was calculated and used while plotting the release and release kinetics curves.
DISSOLUTION KINETICS
Method used to compare dissolution data is:
Model Dependent Methods (zero order, first order, Higuchi and Korsmeyer's- Peppas).
Drug release kinetics
To study the release kinetics, data obtained from in-vitro drug release studies were plotted in various kinetics models: Zero order (equation 1) as Cumulative percentage of drug released Vs Time, First order (equation 2) as Log cumulative percentage of drug unreleased Vs Time, and Higuchi model (equation 3) as Cumulative percentage of drug unreleased Vs Square root of time.
C = K0 t (equation 1)
where K0 is the zero order rate constant expressed in units of concentration/ time and t is the time in hours.
A graph of concentration Vs time would yield a straight line with a slope equal to K0 and intercept the origin of the axis.
log C = log C0 - K t/2.303 (equation 2)
where C0 is the initial concentration of drug,
K is the first order constant, and t is the time.
Q = K t1/2 (equation 3)
where K is the constant reflecting the design variables of the system, t is the time in hours.
Hence, drug release rate is proportional to the reciprocal of the square root of time.
Drug release were plotted in Korsmeyer equation (equation 4) as Log cumulative percentage of drug released Vs Log time, and the exponent n was calculated through the slope of the straight line.
Mt / Mα = K tn (equation 4)
where Mt / Mα is the fractional solute release, t is the release time,
K is a kinetic constant
