Pharmaceutical formulation, in pharmaceutics, is a process in which various chemical substances, along with the active drug, are mixed to produce a final medicinal product. The word formulation is often used in a way that includes the dosage form used in the making.
What Are The Stages And Timeline?
Formulation studies include developing a preparation of the drug which is stable as well as acceptable to the patient. This usually involves adding the drug into a tablet or a capsule for orally administered drugs. It is important to differentiate that a tablet contains a variety of other potentially inert substances apart from the drug itself. Further, studies have to be done to ensure that the encapsulated drug is compatible with these other substances and will not cause harm, either direct or indirect.
Preformulation stage in pharma manufacturing involves the characterization of a drug’s physical, chemical, and mechanical properties to choose what other ingredients or excipients should be used in the preparation. In dealing with protein formulation, the important aspect is to understand the behavior of a given protein under different stress conditions such as freeze/thaw, shear stress, temperature among others to identify mechanisms of degradation and hence its mitigation.
Formulation studies then consider these factors as particle size, pH, polymorphism, and solubility, because all of these can influence bioavailability and in turn, the activity of a drug. The drug should be combined with inactive ingredients by a method to ensure that the quantity of drug added is consistent in each dosage unit, say, each tablet. The dosage must have a uniform appearance, with an acceptable tablet hardness, taste, and capsule disintegration.
Formulation studies will usually not be complete by the time clinical trials commence. This means that simple preparations are initially developed for use in phase I clinical trials.
They typically consist of hand-filled capsules having a small amount of the medicine and a diluent. No proof of the long-term stability of these formulations is necessary, as they will be tested in some days. Consideration has to be given to “drug loading” which is the ratio of the active drug to the total contents of the dose.
A low drug load might result in inhomogeneity problems. On the other hand, a high drug load may result in flow problems or require big capsules if the compound shows a low bulk density.
By the time clinical trials reach phase III, the formulation of the drug should have been developed to be close to the preparation and should be ready to be released for use in the market.
Knowledge of stability is fundamental by this stage, and conditions should have been developed to confirm that the drug is stable in the formulated preparation. If it proves to be unstable, it will invalidate the results from clinical trials since it would not be possible to know what the actual administered dose was. Stability studies are carried out to test if temperature, oxidation, humidity, or photolysis (ultraviolet light or visible light) have any effect, and the drug is examined to see if any degradation products have been formed.
Formulated drugs are typically stored in container closure systems for long periods. The containers include blisters, vials, bottles, syringes, ampules, and cartridges. These can be made from a variety of materials including plastic, glass, and metal. Further, the drug may be stored as a solid, liquid, or gas. Many organizations now provide formulation development services.
It is important to check if any undesired interactions taking place between the drug and the container. For example, if a plastic container is used, tests should be carried out to see whether any of its ingredients become adsorbed on to the plastic and whether any plasticizer, pigments, lubricants, or stabilizers come out of the plastic into the drug. Further, adhesives for the container label should also be tested, to make sure that they do not drain through the container into the preparation.