Strategic formulation development requires reliable early stage in vivo data. Traditional early phase trials on new formulations provide pharmacokinetic data on the drug – but how do we know what the formulation is doing once inside the body? When do oral formulations empty from the stomach? When and in which precise area of the GI tract do they start to break up and what effect does food have on their performance?
Scintigraphy is used to answer all these questions and many more. It is a nuclear imaging technique that allows non-invasive in vivo assessment of the behaviour of oral, nasal, pulmonary and ophthalmic dosage forms, as well as gastric emptying of food.
How does it work?
Formulations are radiolabelled with a low dose of a gamma emitter (commonly 99mTc or 111In) and sequential images of the volunteer or patient are acquired with a gamma camera, allowing visualisation of the dispersion of the radiolabelled formulation in vivo. Prior to the clinical phase, in vitro testing is carried out in order to determine the optimal radiolabelling method for the dosage form in question. This may involve USP dissolution testing, in the case of oral dosage forms, to confirm that the labelling procedure doesn’t alter the physical properties of the system.
What information does it provide?
The radioactive counts within a particular region of interest can be recorded over sequential images, allowing quantification of thedispersion of the radiolabel. The graph below shows quantification of gastric emptying of a radiolabelled meal.
What makes scintigraphy even more powerful is that it can be conducted in parallel with blood sampling to facilitate correlation of PK data with formulation behaviour. The PK data can be interpreted more fully when accompanied by evidence of where the dosage form was located at a given moment and whether it underwent any physical change.
Why is this useful?
The data produced from clinical scintigraphic studies allows informed decision making at the crucial early stages of the formulation development pipeline, as well as supporting claims on formulation performance for marketing or regulatory purposes. Scintigraphy can be used to test the performance of drug delivery systems without the need to incorporate an API. Being able to see how the formulation behaves in the body allows go-no go decisions to be made at an early stage, saving money and reducing the time to market for successful drug delivery systems.
For further information on scintigraphic imaging of drug delivery systems, visit www.bio-images.co.uk
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