Vet360 Vol 4 Issue 3 June 2017 Vet360 - Page 18

PHARMACOLOGY Excipient (Components of a finished drug oth- er than the active pharmaceutical ingredient) Reasons for inclusion Sweetners and flavourings Improve the palatability of oral medocation, to improve compliance in treatment Bulking agents Provides bulk t the formulation to allow for easier handling during dosing or packaging Diluent Brings the formulation to the correct volume of drug per ml of solution/suspension Solubilizers Allows the active ingredient to dissolve in the dilluent Stabilizer Stabilizes the active ingredient and prevents it from chemically degrading Preservative Increase the shelf life of the formulation Wetting agets Allows water to penetrate into a table, so that it can break up and dissolve faster in physiological fluid Lubricants Allows powders to flow through the machines that produce the tablets, without the formulation getting stuck or separation of the active ingredient from the rest of the formulation Chelators Binds certain ions and prevents bacterial growth Antimicrobals Prevent the growth of bacteria Table 1: Some value potential of various excipients in the formulation General types of medicines The principle of generic registration is considered to 1.20 2500 1.00 2000 0.80 In the regulatory system, medicines general fall into three categories: Innovator products, Generic prod- ucts and Compounded products. These three cate- gories are controlled by the Medicines and Related Substance Control Act (Act 101 of 1965): • Innovator Products: Are the first products that are brought onto the market. They are tested as the fi- nal formulation to prove that the active ingredient is properly released and that the formulation is effec- tive. When registered, each indication is looked at individually and requires testing usually with actual clinical cases. The innovator company is general- ly allowed a period of 20 years from patenting, to sell their product with no competition. It is during this period that they recoup their investment. At all times, the manufacturer has to meet strict GMP re- quirements. • A Generic formulation: Is a formulation that con- tains the same active ingredient as the innovator, and is registered through an abbreviated process known as bioequivalence or occasionally thera- peutic equivalence. For the former process, the pharmacokinetics of the generic and the innovator formulation is compared. If the two formulations can be statistically proven to be bioequivalent, it can be registered as a generic to the innovator product. The underlying principle comes from the pharma- cokinetic-pharmacodynamic interactions of the ac- tive mentioned above. If the two drugs allow for the same plasma concentration to be consistently achieved, there’s no reason that they won't have the same effect. Since we do know that the man- ufacture of the formulation can influence the plas- ma pharmacokinetics, the formulation has to meet strict GMP conditions, to ensure batch to batch uni- formity. Generics are thus cheaper than the innova- tor because they don’t have to redo the efficacy and toxicity tests, as these have already been undertaken by the innovator company i.e. why retest for aspects that are already known. Since the pharmacokinetics of the generic formulation is unknown, this is what needs to be tested (Figure 3). With this said, the re- quirements for comparing the pharmacokinetic profiles of the generic to the innovator formulation is still very strict and has to comply with numerous requirements from the study design to the analytical chemistry part of the study. 0.60 0.40 0.20 0.00 -20 0 -0.20 20 40 60 80 1500 1000 500 100 0 Time (h) 0 10 20 30 40 50 Time (h) Figure 3: Illustration of how pharmacokinetics are applied in the process of proving bioequivalence of generic formulations (The graphs in question would be supported by a full statistical evaluation for registration purposes). In this case, two different generic formulations (T) (Each one has its own graph) are compared to the same reference product (R). In each of the