Biopharmaceutical aspects of anti-infective therapy at the extremes of age.

Abstract

Optimal anti-infective therapy at the extremes of age can be supported by the development of appropriate dosage forms. With regard to neonates, infants and children an oral liquid formulation appears to be superior compared with standard formulations such as tablets and capsules, since individualized dosing by body weight or body surface area is more easily achieved. Reformulation of marketed dosage forms, such as crunched tablets or opened capsules, by the hospital pharmacist may result in stability and bioavailability problems and therapeutic failures may be the consequence. With regard to the elderly a reduction in dosing frequency and individualized dosing are important in order to increase compliance. A reduction of dosing frequency can be achieved by oral controlled-release dosage forms, which are designed to release the drug in small amounts at predefined rates. However, to permit ease of swallowing they require a relative small daily dose together with excipients. In addition absorption must occur throughout the entire gastrointestinal tract; this is not the case for several antibiotics. Various advantages and disadvantages of oral liquid and oral controlled-release dosage forms are discussed. In the development of an oral formulation, in addition to a standard tablet a variety of information, such as physico-chemical characteristics, pharmacokinetics and pharmacodynamics must be available. Physico-chemical disadvantages can largely be solved by advanced pharmaceutical concepts, such as the pro-drug approach, complex formation or coprecipitation, which are discussed. Using ciprofloxacin with its long lasting and extremely bitter taste as an example, the pharmaceutical development of an oral liquid formulation and the pharmacokinetic investigations in healthy volunteers are described.