Quality control (QC) is a part of quality management focused on fulfilling quality requirements. It refers to the set of checks or tests carried out during the manufacturing process and before the final products are released to the market to ensure compliance with specifications. QC measures are undertaken to ensure that the finished chewable tablet fulfils the specifications of quality.
Basically, for a finished pharmaceutical product, it should not only be possible to identify and assay the active substance(s), the content of Active Pharmaceutical Ingredient (API) and weight/mass of unit dose should be uniform. The finished products should also be stable under the normal storage condition. Therefore, solid chewable tablets should:
The following important quality control tests are carried out on chewable tablets
Contents
In order to ensure that the preparation actually contains the active ingredient claimed, an identification test, such as infrared (IR) spectrum, ultraviolet (UV) absorption maxima, chromatogram or assay by titration, as specified in the monograph of the drug, should be carried out. For instance, the IR spectrum of a dispersion of the tablet in potassium bromide discs should be concordant with that of the reference standard.
Samples of the product selected at random should be uniform in content of active ingredient to ensure uniformity of dosage. 20 tablets, such other number (not less than 5) as may be indicated in the monograph, are used in the assay but to allow for sampling errors allowances as in the table below are made. The requirements shown in the table apply when the stated limits are 90 to 110%. For limits other than 90 to 110%, proportionately smaller or larger allowances should be made.
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Requirements for adjustments of content of active ingredient of tablets for limits of 90 to 110% [BP, 2009]
Unless otherwise prescribed or justified and authorized, content of active substance less than 2 mg or less than 2 % of the total mass comply with test A for uniformity of content of single-dose preparations. The test A condition is that the tablet preparation complies if each individual content is between the limits of 85.0 % and 115.0 % of the average content. The preparation has failed if more than one is outside of the limits or if one is outside of the limits of 75.0 % to 125.0 % of the average content. If the preparation contains more than one active substance, the requirement applies only to those active substances which correspond to the above conditions.
This test is performed by weighing individually 20 tablets randomly selected from each batch. Not more than 2 deviate from the average weight and non-twice the limit (10% for tablets weighing 80 mg or less; 7.5% for more than 80 mg and less than 250 mg, and 5% for 250 mg or more).
This test is usually not required for chewable tablets.
Although required, there are presently no specific official (BP, USP) conditions for dissolution testing of chewable tablets. The current absence of clear guidance on dissolution rate requirements has led to a situation in which there are no consistent and suitable quality requirements with which the manufacturers of chewable tablets must conform. Regulatory authorities in many countries may be unable to insist on requiring conformity to dissolution rate testing for chewable tablets if international references such as The International Pharmacopoeia do not require it.
The world health organization (WHO), (2011) had aligned with the position of the USP that: “… no product, including suspensions and chewable tablets, should be developed without dissolution or drug release characterization where a solid phase exists”. It goes on to outline the development of in vitro test methods and design of in vivo study protocols. Consistent with the USP, the Food and Drug Administration (FDA) Bioavailability and Bioequivalence Studies for Orally Administered Drug Products – General Considerations (2003), page I7(8), states: “We recommend that rapidly dissolving drug products, such as buccal and sublingual dosage forms (and chewable tablets), be tested for in vitro dissolution and in vivo BA and/or BE. We recommend that chewable tablets (as a whole) be subject to in vitro dissolution testing because they might be swallowed by a patient without proper chewing. In general, we recommend that in vitro dissolution test conditions for chewable tablets be the same as for non-chewable tablets of the same active ingredient or moiety”
A joint position paper (9) by the International Pharmaceutical Federation (FIP) and American Association of Pharmaceutical Scientists (AAPS) reviewed some of the issues concerning dissolution testing of chewable tablets and came up with the statement “…In principle, the test procedure employed for chewable tablets should be the same as that used for regular tablets. This concept is based on the possibility that a patient might swallow the dosage form without proper chewing, in which case the drug would still need to be released to ensure the desired pharmacological action. Where applicable, test conditions would preferably be the same as used for conventional tablets of the same active pharmaceutical ingredient, but because of the non-disintegrating nature of the dosage form, it may be necessary to alter test conditions (e.g., increase the agitation rate) and specifications (e.g., increase the test duration). The reciprocating cylinder (USP apparatus 3) with the addition of glass beads may also provide more “intensive” agitation for in vitro dissolution testing of chewable tablets. As another option, mechanical breaking of chewable tablets prior to exposing the specimen to dissolution testing could be considered. While this option would more closely reflect the administration of the product and the corresponding formulation and manufacturing features, no approach for validating such a method has been reported in the literature…”.
On the basis of this inconclusive situation, WHO made the following propositions:
This test necessary to ensure that they possess suitable mechanical strength to avoid crumbling or breaking on handling or subsequent processing. 20 tablets are used at 25 rpm for 4 min or 100 revolutions in 4 min. Usually, for conventional tablets, a friability value of 1% or less is desirable, while for chewable tablets (due to the lower hardness of the tablets) friability values of up to 4% are acceptable. The test is rejected if any of the tablet caps, laminate or breaks up in the course of the test.
This is measured in terms of load/ pressure required to crush a tablet when placed on its edge. The hardness of chewable tablets should be such that they withstand the rigour of manufacturing, packaging, shipping and distribution, as well as be easily chewed by the intended patient population. Based on the review of applications and literature sources, FDA recommends that hardness for chewable tablets be kept low (e.g., <12 kp). Higher hardness values may be considered if justified.
These involve assessment of properties such as taste, mouth-feel, colour and odour. The results provide information about appearance of the product and possibly its palatability and acceptability, or otherwise.
This test involves the use of individual sensory (taste) organs to assess the intrinsic taste property of the chewable tablet formulation. The taste may be attributed to the API and/or additives, especially the flavouring and sweetening agents. Therefore, this property helps to identify and characterize the taste of the product. Normally, a product may be described as sweet, bitter, sour, astringent or salty. But usually, the bitter taste of the formulation is rated using the Hedonic scale.
The following procedure may be adopted/followed using a single-blind study design to test for the taste of a chewable tablet formulation in the buccal cavity.
The taste would be considered acceptable when the score is l or less. The bitterness of the formulation is not acceptable if the score is higher than 1.
The term mouth-feel is related to the type of sensation or touch that a tablet produces in the mouth upon chewing. As such, it has nothing to do with chemical stimulation of olfactory nerves or taste buds. Mouth-feel test could be conducted immediately after the taste test. The same human volunteers who participated in the taste evaluation test may be asked to give their opinion about the feeling of smoothness or grittiness (i.e., texture) of the dispersion soon after chewing the tablet. The tablet is held and rubbed between the first and forefingers to determine the feel. It may be gently broken down into granules with mortar and pestle before testing the texture. In general, gritty or gummy textures are undesirable, whereas a soothing and cooling sensation with smooth texture is preferred.
Colour has also been used as a means of identifying certain pharmaceutical products. The test could be done using six human volunteers. Place a unit dose (tablet) on a clean white background (paper) and ask them to assess the colour.
Odour is also characteristic of certain APIs and excipients, so may be used as a means of identification. Six human volunteers that have no pathological condition of the nose could be selected for the test. A unit dose (tablet) is held close to the nose by each participant using a clean Spatula, forceps or fingers and the odour perceived. A product may be described as sweet smelling, foul-smelling or aromatic.
This test is performed to assess the ease of chewing the tablet. In a simple procedure involving a panel of six human volunteers, the product may be described as easy, a little hard or very hard to chew on a scale of 5, 3 and 1, respectively.
The stability of a chewable tablet formulation is important mainly for safety of the consumer and maintenance of quality over its shelf-life. It is also important so as to avoid economic losses to the manufacturer and for compliance with regulatory requirements. Result of stability testing guides the establishment of storage conditions and shelf-life of the product.
Change in organoleptic properties including physical appearance (e.g., mottling) may indicate physical and/or chemical instability due to certain factors such as hydrolysis, oxidation, decarboxylation, absorption of carbon dioxide, isomerization, and polymerization. Many of these causative factors are encouraged by environmental conditions; this underscores the import of compliance with appropriate packaging and storage requirements for adequate protection of the product.
Stability testing is categorized into: stress, accelerated and real time studies, all involving exposure to varying climatic conditions especially temperature (heat), humidity (moisture), light, pH, and checking the concentration of active ingredient as well as other parameters. Briefly, stress test involves exposure to high temp and humidity, e.g., 40-45°C at 75% relative humidity (RH) for a few hours. Accelerated stability test involves exposure to high temp and humidity, 40-45 °C at 75% RH, for some hours to 1-6 months while for real time test the product is exposed to actual (real) storage conditions for a period of l to a minimum of 3 yrs.
Other tests carried out to ensure quality of the chewable tablets include uniformity of thickness, uniformity of diameter and measurement of tablet density.
Read More: Quality control of Pharmaceutical Tablets
Chewable tablets represent an example of a specialized tablet type specifically designed to be chewed in the mouth before swallowing. They must be subjected to a number of tests before they are approved for consumption and marketing.
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