Journal of Controlled Release, 1985, Vol.2, pp.27-38
The design and evaluation of delivery systems for the gastrointestinal tract requires knowledge about three inter-related topics, the drug, the delivery system and the destination intended. Preformulation data describing the physicochemical characteristics of a drug molecule need to be considered in relation to known physiological variables such as gastrointestinal pH gradients and transit times. The drug progabide, which is unstable under acid conditions, is used to illustrate the delicate balance between physical and physiological variables and the use of physical models describing the biopharmaceutics and pharmacokinetic events for the design of an appropriate delivery system. Similarly, the use of in vitro dissolution tests and diffusion experiments can provide essential information on the mechanisms of drug release but are not necessarily good predictors of the in vivo situation. The non-invasive technique of gamma scintigraphy has been used to follow in vivo release rates and to relate these to pharmacokinetic parameters. The same scintigraphic method has been used to follow the gastrointestinal transit of a variety of controlled release systems to include pellets, matrix systems and osmotic pumps. The effect of dosage characteristics and physiological variables, particularly diet, can be evaluated. Large (〉5 mm) units will be retained in a fed stomach while smaller units can empty in a similar way to liquids. Small intestine transit time is short (3 h ± 1 h ) for all systems studied. This result has implications for the design of controlled release delivery systems for drugs with poor absorption in the large intestine, as well as for the development of positioned release systems (colon targeting).
Pharmacy, Therapeutics, & Pharmacology
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