Quality control of suspensions

A number of procedures have been suggested in the past for evaluating the physical stability of suspensions. Some of these are empirical in the sense that they have no mathematical base. Some methods currently being used are so drastic that they destroy the structure of the suspension. The methods used may be categorized as:

(a) Sedimentation methods:

 Since formation of the sediment and its redispersibility are two features related to the overall acceptability of suspensions, many evaluation procedures centre around sedimentation properties.

The simplest procedure for evaluation is to keep a measured volume of the suspension in a graduated cylinder in an undisturbed state for a certain period of time and note the volume of the sediment, which is expressed as ultimate height (hu). This, in relation to the initial volume of the suspension, (Ho) is expressed as sedimentation ratio. It should, however, be noted that sedimentation ratio (hu/Ho) is dependent on time and it is likely to vary at different periods of time. The sedimentation ratios at different periods of time can be plotted against time abscissa to give a curve that indicates the sedimentation pattern on storage. If the curve is horizontal to time axis it indicates a better suspension. However, if it steeps down it indicates a poor formulation. Sometimes it may be useful to dilute original suspension to known extents before determination of sedimentation ratios.

(b) Rheological methods:

 Evaluation of rheological behaviour of the suspension can help in predicting the settling pattern and can also provide clues to vehicle particle structure. In carrying out rheological study of a suspension generally low shear rates are employed and samples are evaluated undisturbed. By use of a Brookfield viscometer with T-spindle the rheological reatures at different depths in a sample can be studies. Data collected on samples stored for various periods of time can give useful information about the stability of the suspension.

(c) Electrokinetic methods:

 As has been discussed in the chapter on emulsions, the surface electric charge or zeta potential is instrumental in deciding the stability of disperse phase systems. Certain zeta potentials produce more stable suspension because of controlled flocculation. Hence, determination of zeta potential of a suspension can give valuable clues to its stability. The migration velocities of particles can be measured by electrophoretic methods and zeta potential calculated from it.

(d) Micromeritic methods: 

In the ultimate, the stability of a suspension is inter-related to the size of particles constituting its disperse phase. A growth in the particle size is a pointer towards its instability since such an occurrence can ultimately result in the formation of lumps or cake destroying the physical structure of a suspension and rendering it useless. Hence, an appreciation of change in particle size with passage of time can provide an insight into the stability aspect of a suspension. Changes in absolute particle size, particle size distribution, crystal habit etc. can be worked out by microscopy, coulter counter etc.

Quality control of capsules

The evaluation of capsules, in general, follows the line for compressed tablets and tests like the weight variations test, content uniformity test, disintegration and dissolution time.

Weight variation : 

This test is done by taking 20 capsules individually, determining average weight per capsule and finding out weight variation of each capsule against the average value(± 10% variations are permitted). However, if the variations are beyond this limit net weight of contents of each capsule should be determined, and compared with average net weight. This will remove any doubt about the possible variation in the weights of individual shells. As per standards specified in some Pharmacopoeias net weight of not more than two capsules should differ by more than ± 10% from the average net weight and no capsule should differ by more than ± 25%. If the average net weights of 2 to 6 capsules deviate by ± 10 to 25%, net weights of 40 more capsules should be determined. In a total of 60 capsules not more than six should deviate from average by more than ± 10% and none by more than ±25%.

Disintegration and dissolution time :

 Capsules are not normally tested for disintegration as their shells are known to dissolve rapidly in the gastric fluids. However, capsules which are designed to be enteric, by treatment of their shells with formaldehyde, should be tested thus to ensure than they do not disintegrate in simulated gastric juice under simulated conditions. Dissolution time tests are run on the lines of compressed tablets. Any of the standard apparatus available for dissolution tests can be employed. The determination of dissolution time is important since absorption of drugs depends upon their dissolution times.

Drug content uniformity :

 In solid dosage forms uniform distribution of medicaments remains a problem. The problem becomes more acute with potent medicaments administered in low doses. Hence, a number of capsules should be selected and assayed for drug content individually. Pharmacopoeias specify 30 capsules out of which 10 should be assayed individually in the first instance. Out of these at least 9 should be within ±15% of average and none should be beyond ±25. If 1 to 3 capsules out of the 10 assayed originally fall outside ±15% the remaining 20 should be assayed. Out of the total 30 capsules at least 27 should be within ±15% and no capsule should be beyond ±25%.

Quality control of tablets

Tablets may be evaluated for their physical characteristics, drug contents, dissolution sites, rate of release of drug etc. Certain physical properties of drugs like uniformity of weight, hardness, friability, thickness, disintegration and dissolution times are important characteristics having a bearing on their handling and use.

(1) Weight Uniformity:

It is desirable that every individual tablet in a batch is uniform in weight, and the weight variation, if any, is within the permissible limits (generally ± 5% for tablets weighing more than 325 mg). Non-uniformity in weights can lead to variation in dosaging. Hence, all finished bathes of tablets should be sampled and tested for weight uniformity. Generally 20 tablets are weighed collectively and individually. From the collective weight average weight per tablet is calculated. The weights of individual tablets are then compared with the average weight to ascertain whether the variations in weights are within permissible limits or not. Some of the basic causes of weight variation of tablets are faulty incorporation of glidants and resultant poor flow of granules, wide variations in granule sizes, differences in lower punch length, improper lubricants etc.

(2) Hardness :

hardness of a tablet is indicative of its tensile strength and is measured in terms of load/pressure required to crush it when placed on its edge. A number of handy hardness testers such as, Mosanto type or Pfizer type are currently in use. A tablet hardness of about 5 kg is considered to be minimum for uncoated tablets for mechanical stability. The hardness is a function of physical properties of granules like their hardness and deformation under load, binders and above all the compressional force. The hardness has influence on disintegration and dissolution times and is as such a factor that may affect bioavailabilities.

(3) Thickness :

The thickness of a tablet depends mainly upon die filling, physical properties of materials to be compressed and compressional forces. There is bound to be a small variation in the thicknesses of individual tablets in a batch but it should be of such an order that it does not immediately become apparent to unaided eye. The thickness can be easily measured by micrometers or in holding trays with sliding caliper scale. Thickness should not vary beyond ± 5% of the standard value.

(4) Friability :

Friability generally refers to loss in weight of tablets in the containers due to removal of fine particles from their surfaces. However, in wider sense chipping and fragmentations can also be included in friability. Friability generally reflects poor cohesion o tablet ingredients. Standard devices have been fabricated to measure friabilities. Generally such instruments, marketed as `Friability Test Apparatus’ or `Friabilators’, consist of a circular plastic chamber, divided into 2-3 compartments. The chamber rotates at a speed of 25 r.p.m. and drops the tablets by a distance of 15 cms. Preweighed tablets are placed in the apparatus which is given 100 revolutions after which the tablets are weighed once again. The difference in the two weights represents friability. The weight loss should not be more than one percent.