From bench to bedside : designing oral drug formulations

Wilson, Clive (2012) From bench to bedside : designing oral drug formulations. Eesti Arst, 91 (9). 470–477.

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Abstract

The development of drugs over the last twenty years has yielded candidates which are more potent, but are more difficult to formulate into oral medicines. In addition, there is enthusiasm for employing extended release or colon targeted dosage forms for which the utility of in vitro tests is extremely limited. Modern dose form design has turned to the adoption of clinical techniques, especially gamma scintigraphy, in which a non-absorbed additive such as a technetium-99m labelled radiopharmaceutical is added to the formulation. This allows the position of the formulation to be related to the plasma concentration-time profile so that each administration provides the maximum amount of information. Other techniques including magnetic resonance imaging and magnetic moment imaging are also useful. Variability in drug absorption in patients is a mix of physiological factors such as posture, the time of feeding relative to the dose and bowel habit together with factors imposed by formulation constraints: the need for water for disintegration and dissolution and the amount of agitation. Imaging techniques are extremely useful in disassembling these additive factors. Bench to bedside prediction is the ultimate goal but the inf luence of daily activity has to be borne in mind in formulation design.