COMPARISON OF SOME PHYSICAL PARAMETERS OF WHOLE AND SCORED LISINOPRIL AND LISINOPRIL / HYDROCHLORTHIAZIDE TABLETS Introduction Tablets

Tablets are one of the most popular and preferred solid dosage forms because they can be accurately dosed, easily manufactured and packaged on a large scale, have good physical and chemical stability, and can contribute to good patient compliance given their ease of administration. Th e ability to match doses to patients depends on the availability of multiple dose sizes and adequate dose-response information. Th ese are not always provided, so splitting of the tablets is sometimes necessary. Tablet splitting is an accepted practice in dispensing medication. It has been used when a dosage form of the required strength is not available commercially. Th e aim of our study was to compare some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets and to accept or exclude their infl uence on the obtaining of re-


Introduction
Tablets are one of the most popular and preferred solid dosage forms because they can be accurately dosed, easily manufactured and packaged on a large scale, have good physical and chemical stability, and can contribute to good patient compliance given their ease of administration ().Th e ability to match doses to patients depends on the availability of multiple dose sizes and adequate doseresponse information.Th ese are not always provided, so splitting of the tablets is sometimes necessary ().Tablet splitting is an accepted practice in dispensing medication.It has been used when a dosage form of the required strength is not available commercially ().
Scored tablets provide dose fl exibility, ease of swallowing and may reduce the costs of medication.However, many patients are confronted with scored tablets that are broken unequally and with diffi culty, reducing compliance and reliance on the drug.Possibilities to reduce breaking difficulties are breaking instructions, tabletsplitters and breaking in advance.Factors infl uencing the performance of score lines are shape, size, curvature and thickness of the tablet and the form and deepness of the score line.Performance of score lines can be defined by breaking ease, uniformity of mass of subdivided tablets and loss of mass by the subdivision ().
The process of splitting tablets cases a number of problems, some of which are patient related while others are related to the tablet or formulation.Uneven splitting of a tablet may result in signifi cant fl uctuations in the administered dose.This may be clinically significant for drugs with a narrow therapeutic range.For many drugs, especially those with long half-lives and/or a wide therapeutic range, dose fluctuations are unlikely to be clinically significant (, ).
Lisinopril tablets labelled strength ,  and  mg and lisinopril/hydrochlorothiazide tablets labelled to contain /, mg (in all cases samples were scored tablets) were used as a model for our study.
The aim of our study was to compare some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets and to accept or exclude their influence on the obtaining of required dosage.The following tests were provided: friability, tablet hardness and disintegration testing for whole and scored tablets and mass uniformity as well.

Materials
Th e tablets used for this study were commercially available, obtained from the same producer and purchased from the local pharmacy.Four different batches of scored tablets were used: Batch I-lisinopril tablets, labelled strength  mg; Batch II-lisinopril tablets, labelled strength  mg; Batch III-lisinopril tablets, labelled strength  mg; Batch IV-lisinopril/hydrochlorthiazide tablets, labelled strength /, mg

Crushing strength testing
The tablet is placed between the jaws, taking into account the shape, the break mark and the inscription.Th e tablet was oriented in the same way with respect to the direction of application of the force.The measurement was carried out on  tablets, taking care that all fragments have been removed before each determination.The results are expressed in the values of the forces measured, all expressed in newtons.Th e crushing strength was determined using hardness tester (type TBH , Erweka, Apparatebau, Germany).

Friability testing
Twenty tablets were placed on a sieve, and any loose dust was removed with the aid of the brush.Th e tablet sample was accurately weight and placed in the drum.It was rotated  times, and the tablets were taken out.Any loose dust from the tablets was removed as before.Th e friability is expressed as the loss of the mass and it is calculated as a percentage of the initial mass.Th e friability was determined using Roche friability tester (Erweka, Apparatebau, Germany).

Breakability test methods
Th e following manual breakability test was performed; the tablet was held between the thumb and the index finger of each hand on either side of the score line, with the score line facing upwards and without using the nail.Separation into two halves was done by breaking open the tablet at the score line side.

Mass uniformity testing
Th irty tablet units were taken at random and weight individually.Additional  tablets were taken at random EDINA VRANIĆ, ALIJA UZUNOVIĆ: COMPARISON OF SOME PHYSICAL PARAMETERS OF WHOLE AND SCORED LISINOPRIL AND LISINOPRIL/HYDROCHLORTHIAZIDE TABLETS and broken manually.All the parts obtained from one tablet were used for the test.Each of the thirty parts were weight individually and the average mass calculated.Th e same procedure was done with the remaining thirty parts.

Disintegration testing
Th e following disintegration test was performed; in each of six tubes, one tablet is placed.Th e assembly was suspended in the  litre beaker, containing water, and operated for  min.A suitable device maintained temperature of the liquid at -oC.Th e test was provided using ZT  disintegration tester (Erweka, Apparatebau, Germany).

Results and Discussion
The results of resistance to crushing of tablets, friability testing and disintegration time per batch are presented in Hardness values, indicating good mechanical properties for whole tablets that are able to withstand handling.It is obvious from the results for the hardness value of halved tablets, that resistance to crushing of tablets showed broad variation (comparing values for relative standard deviation for whole and halved tablets).
During the compaction or pressing of pharmaceutical powders into tablets, the quality of the resulting tablets depends on die aspect ratio and geometry, the forces of the upper and lower punch, the speed at which this force is applied, the length of time for which the force is applied, and the powder properties of compressibility, permeability, friction and cohesion within the powder, and friction and adhesion between the powder and the die walls and punches.In particular, excessive die wall friction may promote uneven disposition of the compressive force throughout the powder, resulting in heterogeneity of density within the tablet.Th e tensile strength of a tablet depends on the bonding strength between particles within the tablet.Particle size and shape can affect how particles pack together during compression, and how well the particle surfaces interact to create stronger or weaker bonds.Under compression, brittle particles may break or shatter, while softer particles may undergo deformation to fi ll gaps between the particles.Th e strength of the interparticulate bonds formed during compaction can be aff ected by the brittleness/elasticity of the material, and the rate of tablet compression.The act of compacting powders stores energy within the tablets, by shifting or compressing the intermolecular bonds within the particles.Th e tablets have a natural tendency to relax once pressure is removed, and this tendency works against the interparticle bonding formed during compression.Hardness testing procedure causes irreversible changes in this structure.
Up to now, no regulatory requirements for the maximum loss of mass upon breaking exist.In view of the results reported for loss of mass on breaking () and in line with Ph.Eur.requirements on friability, we consider a loss of  acceptable.All samples (whole and halved tablets) meet this requirement (Table ).

Table 
, ,  and .Mass uniformity analysis of whole and scored tablets (Batch I, Batch II, Batch III, Batch IV) is presented in Table.TABLE 1. Resistance to crushing of tablets, friability testing and disintegration time per Batch I (lisinopril tablets-labelled strength 5 mg)-whole and halved tablets TABLE 2. Resistance to crushing of tablets, friability testing and disintegration time per Batch II (lisinopril tablets-labelled strength 10 mg)-whole and halved tablets TABLE 3. Resistance to crushing of tablets, friability testing and disintegration time per Batch III (lisinopril tablets-labelled strength 20 mg)-whole and halved tablets

TABLE 4 .
Resistance to crushing of tablets, friability testing and disintegration time per Batch IV (lisinopril/ hydrochlothiazide tablets labelled strength 20/12,5 mg)-whole and halved tablets EDINA VRANIĆ, ALIJA UZUNOVIĆ: COMPARISON OF SOME PHYSICAL PARAMETERS OF WHOLE AND SCORED LISINOPRIL AND LISINOPRIL/HYDROCHLORTHIAZIDE TABLETS