Drug substance tablets

M. J. Walters and W. E. Dunbar, High-performance liquid chromatographic analysis of hydrocortisone drug substance, tablets, and enema, J. Pharm. Sci., 77 446(1982). 

Rufloxacin hydrochloride Drug substance, tablets CZE Sodium borate, pH 8.8... 

Ximelagatran Drug substance, tablets Sodium phosphate, pH 1.9, 10% acetonitrile, llmmoll HP- -CD LOQ 0.05%... 

In-vitro bioavailahility tests usually form part of the criteria for evaluating the individual batches of a product. These are based on monitoring the rate of release of the drug substance from the pharmaceutical form, usually by observing the dissolution rates of tablets or capsules. 

Initial Situation An experimental granulation technique is to be evaluated a sample of tablets of the hrst trial run is sent to the analytical laboratory for the standard batch analysis prescribed for this kind of product, including content uniformity (homogeneity of the drug substance on a tablet-to-tablet basis, see USP Section (905)" ), tablet dissolution, friability (abrassion resistance), hardness, and weight. The last two tests require little time and were therefore done first. (Note Hardness data is either given in [kg-force] or [N], with 1 kg = 9.81 Newton). 

Often it is unnecessary to calculate an exact value for an absorption rate constant. For example, when several oral tablets containing the same drug substance are all found to be completely absorbed, it may be sufficient to merely determine if the absorption rates are similar to conclude that the products would be therapeutically equivalent. In another instance, it would be possible to choose between an elixir and a sustained-release tablet for a specific therapeutic need without assigning accurate numbers to the absorption rate constant for the two dosage forms. 

Incompatibilities have also been observed in solid dosage forms. A typical tablet contain binders, disin-tegrants, lubricants and fillers. Compatibility screening for a new drug should consider two or more excipients from each class. Serajuddin et al. have developed a drug-excipient compatibility screening model to predict interactions of drug substances with excipients [49],... 

Class I recalls are those that have been judged to present a serious threat to the health of the consumer. Examples of this type of recall include brewers yeast tablets (product contaminated with Salmonella), defective pacemakers (electronically unsafe), and numerous cases of mislabeling of drug substances, such as the belladonna alkaloids [20]. 

The moisture uptake models we have discussed have been concerned with pure components. The deliquescing material could be a drug substance or an excipient material. In pharmaceuticals, however, mixtures of materials are also important. One possible situation involves mixing nondeliquescing and deliquescing materials that are formed into a porous tablet or powder blend. The obvious question is, Do the models for pure components apply to porous heterogeneous materials For pure components we have assumed that the mass and heat limiting transport... 

Studies involving instrumented compaction equipment can be extremely useful in the development of dosage forms, especially when the amount of drug substance is limited in quantity. Marshall has described a program in which dynamic studies of powder compaction can be used at all stages of the development process to acquire formulation information [63]. The initial experiments include a determination of the intrinsic compactability of the compound. In subsequent work, simple tablets are prepared, and tested for dissolution, potency, and content uniformity. Through studies of the compaction mechanism, it becomes possible to deduce means to improve the formulation under study. 

Tablet excipient interactions are occasionally observed when evaluating a drug product for purity. Since there are many excipients in a typical pharmaceutical tablet, known bands need to be identified to make it easier to evaluate for degradation products. Unfortunately, occasionally an inert excipient may react with a derivatizing agent used in TLC making this entity appear as a band that now needs to be identified. In Fig. 13.33, a placebo tablet, an extracted tablet, a handmade tablet blend of all components, and the drug substance standard are all applied to the same HPTLC plate and developed. These results alert the analyst to any excipients that may interfere in the evaluation of the tablet for purity. In this case, the only bands observed in the tablet blend and extracted tablet are the same bands seen in the tablet blend.

If an excipient had been observed, it would need to be identified. In Fig. 13.34, the drug substance standard is applied on lane 1 next to the extracted tablet. The remaining lanes labeled 2-12 are individual excipients in this particular tablet. Only one excipient, number 6, appears and it does in fact have the same R value as the band observed in the tablet. This confirmatory test is commonly used to identify interfering excipients. Now this band can be labeled appropriately, rather than mistakenly labeled as a degradant or impurity. 

The final step in a tablet purity experiment is to determine if all of the drug substance was extracted from the tablet, and if some adhered to the filter used in the extraction process. A sample of drug substance is prepared at nominal concentration, typically 25 mg/ml and diluted to make a standard that is 0.5% of nominal concentration, or 0.125 mg/ml. 

Whether physical mixtures represent real drug-excipient(s) interactions in a capsule or tablet formulation has been debated.57 The use of prototype formulations instead of physical mixtures has been suggested. However, drug substance availability and practicality may limit... 

The protection of a drug substance from the destructive influences of atmospheric oxygen or humidity (such as coated tablets, sealed ampuls)... 

The concealment of the bitter, salty, or offensive taste or odor of a drug substance (such as capsules, coated tablets, flavored syrups)... 

---