Vet360 Vol 4 Issue 3 June 2017 Vet360 - Page 17

PHARMACOLOGY only the ability to reach said concentration that is impor- tant, but the duration of time that the concentration can be achieved). mulations. The same can be said if a different form of the active (e.g. different salt, different size of molec- ular, different polymorph, different isomer) is in use. As one can see, since the drug concentration at the recep- tor site is important, and that the drug pharmacokinetics determines the drug concentration in the body, these the two process must interact to produce a drug effect. More importantly this principle states that if two drugs achieve the same concentration in the plasma, they should be equally as effective. As a given rule, no two formulations are identical un- til proven i.e. simply being told that formulation has the same active as another product is not sufficient to assume efficacy. This would need to be proven with validate methodology such as bioequivalence testing. Another important factor to be consider is the po- tential for the inactive and active to interact with one another with resultant inactivation, or change in tab- letting pressure that precludes the release of the ac- tive ingredient in the same period of time, or even the incorrect pH which can cause pain and tissue damage on administration. The formulation Medication that are sold commercially, are sold as a mixture of ingredients that all interact to allow the said drug to have its effect. The formulation is there to ensure that the drug is adequately absorbed into the circulation and it can also control the rate of absorption. To place this into perspec- tive, the formulation controls the time to a drug’s first effect, the degree of effect and thus the degree of side effects. The formulation has a number of potential components, which all fulfil different roles in allowing the active ingredient to be absorbed, as well as the shelf-life of the drug (Table 1). Another important feature of the formulation is the actual chemical properties of the active ingredient, which also has an impact on drug absorption, chemical stability, interaction with excipients and at times even activity. For the latter it's’ important to note that the active ingredient can also occur in different forms (e.g. amorphous versus crystalline) with some chemical forms being ineffective. The same can apply for chirals (L and D Isomers) with some isomers being inac- tive, more act ive or even toxic (e.g. dexmedetomidine is the active chiral of medetomidine). Since we know that the formulation effect is extreme- ly important, drug manufacturers have to ensure that their formulations are as uniform as possible. Most try and keep their drugs within a 5% variation of the ex- pected from batch to batch (e.g a 5mg tablet may have 4.75 to 5.25 mg therein), which is lower than natural variation which can be as high as 10%. This process of control is known as Good Manufacturing Practice (GMP), and involves standardising as many factors as possible, from how the chemicals are sourced to how the equipment is handled, serviced and calibrated. It expects the manufacturer to undertake routine assays of their formulation at various steps in manufacture as well to ensure that staff are adequately trained. From numerous pharmaceutical studies, we know that a change in the excipients or a change in the ratio of ingredi- ents can result in different absorption profiles between for- Other important aspects include the source and pu- rity of the chemicals in use e.g. what's the purity, is it free of endotoxins, it is free of contaminants, it is free of bacteria, etc. While this process does add to the costs of production, it is well known that without these control measures the variation in the formula- tion can result in unpredictable variations in plasma concentrations, which could translate to ineffective treatment, treatment being toxic or even inconsistent treatment where one dose works and another fails. Figure 1 Figure 2: Interaction of the formulation effect, pharmacokinet- ics and pharmacodynamics of the drug. The figure shows the importance of the formulation in controlling the subsequent pharmacokinetic profile of the drug and its effect concentration achieved at the biophase. PK=Pharmacokinetics. PD= Pharma- codynamics. In the formulation, the actives and inactives will interact with one another to control absorption (Figure 2). Issue 03 | JUNE 2017 | 17