QC LABORATORY AT A GLANCE - Part 2

As a Quality Control "QC" professional responsible for important part of "conform-non conform" cycle for all production inputs and outputs you can predict a huge working stress!

Speaking about the QC role? Why QC is so important? How does QC laboratory perform and fit to the manufacturing facility system? Finally, how to manage the total view of QC and avoid mistakes in the laboratory affecting instruments, performance or accuracy? Those points and interesting details to be covered in this concise series of 3 articles entitled: "QC laboratory at a glance". We discussed in the last article (part 1) the role of QC, general categories of tests and the integrated roles of QA and QC. In part 2 we will focus on specific tests for a specific dosage form to feel involved in the day of a QC analyst!!

Tablets dosage form QC

Basic knowledge

As mentioned in part 1, UNIVERSAL TESTS are: IDENTIFICATION TESTING, ASSAY, UNIFORMITY OF DOSAGE UNIT, IMPURITIES, MICROBIOLOGICAL EXAMINATION and we can add ALCOHOL CONTENT in case of liquids containing alcohol.

Now, after we mentioned the universal tests required. What are the "dosage forms"-related tests? It is this article we should highlight examples of such tests for some of famous dosage forms mentioning the most important tests required for such dosage forms which when added to the universal tests give us a high certainty in the quality.

Tablets

Although we can find triturated tablet dosage form in old schools of pharmacy education and 3-D printed tablets in high technology advanced industry or research, COMPRESSED TABLETS still the major type of tablets produced in the industry. After passing the physical description criteria, most of compressed tablets need Friability test, conducted on uncoated tablets to ensure its ability to be either transported or coated without fraction or without missing parts affecting its weight. The limit of this test is recommended to be 1% as a maximum allowable weight loss from the tablets. Another important test for tablets (conducted normally on uncoated tablets, also) is the Breaking force test which is commonly known as Hardness test, this test ensures a balanced compression force enabling the tablet to endure the transportation or coating processes and to achieve acceptable disintegration and dissolution results when tested. Disintegration test means, in brief, that the tablet becomes small particles when immersed in the immersion fluid used in disintegration tester. This is important to facilitate the dissolving of the drug enabling it to be efficacious. It is accepted according to British Pharmacopoeia that uncoated tablets disintegrate within 15 minutes and the coated tablets disintegrate within 30 minutes. Here, we need an important question: is it enough to disintegrate without ensuring that active pharmaceutical ingredient "API" (the drug substance) is actually dissolved? The answer is: No!

Dissolving of the API from a solid dosage form (or even a liquid dosage forms containing solid suspended particles) is a critical process in its aimed efficacy, so a dissolution test is a cornerstone test for tablets. Dissolution test is the test by which the analyst ensures that the API is dissolved in a warm suitable medium under mild controlled conditions of agitation and this gives us some information about the predicted behavior of the tablet in the body of the patient. This relation between such important test and the biological performance of the dosage form gives the dissolution test a critical importance and gives it the special naming: PERFORMANCE TEST. Of course it is a very broad field in science to evaluate the association and the degree of correlation between the in vitro dissolution test (laboratory test) and the relevant in vivo performance (behavior inside the human body reaching the blood stream to give the effect), but dissolution is the very simple method which we can depend on for this purpose in routine QC work. Worthy to mention that: disintegration can be the performance test instead of the dissolution in special cases. Water content here is a an important test which is normally required to ensure limited water content in the tablets especially in case of hygroscopic drugs and/ or the tablets granulated using water during manufacturing.

Another important question, does dissolution test is only for tablets? Let we answer it in the next section of suspension dosage forms.

Suspension

Suspension is a liquid dosage form comprised of a suitable liquid containing the solid particles of the drug suspended not completely dissolved. Answering the last question, dissolution test is required for such dosage form to ensure the dissolving of such solid particles until reaching a true solution. Another important test for aqueous liquid dosage form including suspensions is pH test. The pH is an expression of the degree of acidity in a ruler of 14, where the mid- point 7 means neutral, lower than 7 means acidic and higher than 7 means alkaline. If the suspension is viscous it needs a viscosity testing. Predetermined specifications of pH and viscosity for the liquid aqueous product should be achieved. Also, a deliverable volume test is required to ensure that the bottles going the patients contain the right amount of liquid, moreover, the uniformity of the dose is checked, typically if the product has provided at manufacture with a measuring device a Uniformity of mass of delivered doses from multidose containers to be performed. Resuspendability testing for the product should be conducted to ensure that the formula enabled enough time for dosing while particles of the drug are suspended. Worthy to notice that special suspensions are for nasal, inhalational or parenteral administration and so need special required more tests. Finally, an acid Neutralizing capacity test should be passed to ensure the capacity of the product to neutralize the acidity.

Creams

Going from tablet (as an example of solid dosage forms) and suspensions (as an example of liquid dosage forms) we will discuss an attractive example from the semi-solid category: the cream. Medicated creams are products containing the drug substances in a semi-solid vehicle and it may me oil in water vehicle, i.e., the external phase is aqueous phase and the internal phase is oily to dissolve the lipophilic drug. Also, it may be water in oil type containing the drug solubilized in the aqueous phase. After passing the physical properties and achieving neither separation not grittiness in its texture, Apparent viscosity testing is need for creams and pH is required for oil in water creams (as mentioned in liquid dosage forms, the aqueous liquids is a subject for pH testing). Water content here is a test needed as per solid dosage forms and has its limit according to the manufacturer requirements. Finally, Minimum fill testing is required to ensure that each unit has the right amount and so, the patient receives the suitable amount covering the planned duration of treatment.

Generally, the tests required for each dosage form are written and revised in a structured manner to resemble the formal specifications of the product which should be achieved keeping the drug effective, safe and with accepted quality.

In the next article, we will summarize the QC issue and have a top view on management and avoiding mistakes of such important lab. Stay tuned!