Impact of Formulation on Ciprofloxacin Oral Absorption
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research is to see if certain tablet formulation factors affect oral drug
      absorption. Medications taken by mouth, such as tablets, need to be absorbed into the body in
      order to do any good. Tablets contain a drug, but also contain non-drug ingredients that are
      called excipients or fillers. Excipients in the tablet, and the way in which the tablet is
      manufactured, both can impact how much drug is absorbed into the body. That is, tablet
      formulation factors can cause a tablet to be effective or not effective.

      Tablets in this research contain the drug ciprofloxacin hydrochloride. Ciprofloxacin is an
      antibiotic to treat infections, such as lung infections. This drug is being used since it has
      low water solubility and is probably sensitive to tablet formulation factors.
    

Detailed description: 
      Dogs and humans exhibit differences in gastrointestinal physiology. The development of
      pharmaceuticals for both humans and dogs typically depends upon pharmacokinetic studies in
      the other species. Product design and quality attributes for dogs (and for humans)generally
      conduct such extrapolations in a simplistic fashion, without a systematic account of the
      differential intestinal physiology between dog and human. This project aims to elucidate
      product quality differences between human and dog oral solid dosage forms as a result of the
      differential physiology between the two specifies. This insight will facilitate the
      regulation of canine medicines by highlighting how product standards for human medicines are
      either too liberal or too restrictive for canine medicines.

      Ciprofloxacin hydrochloride will be used as a model poorly soluble drug. A range of
      immediate-release (IR) tablets will be formulated to map the design space. Formulations will
      be fast, medium, and slow, with respect to dissolution rate of drug. Ciprofloxacin is
      expected to exhibit formulation-dependent pharmacokinetics, which is additionally impacted by
      the differential physiology between dog and humans. In particular, the investigators
      anticipate a greater sensitivity to formulation for dogs than for humans. Consequently, the
      investigators anticipate dogs to be more sensitive to formulations, where such critical
      formulation factors must be considered in canine product design and regulation.

      Objectives: 1) The primary objective of this human study is to assess whether specific
      formulation factors impact the rate and extent of ciprofloxacin oral absorption, as well as
      the absolute absorption profile of ciprofloxacin. 2) The secondary objective is to assess if
      dogs exhibit a greater sensitivity to formulation than do humans.

      Hypotheses: The investigators anticipate that humans exhibit a modest sensitivity to specific
      tablet formulation factors. 1) Hence, the hypothesis of this human study is that humans do
      not exhibit a sensitivity to specific formulation factors and show no in vitro - in vivo
      correlation to dissolution rate. 2) Alternative hypothesis is that humans do exhibit a
      sensitivity to specific formulation factors and show an in vitro - in vivo correlation to
      dissolution rate.
    

Intervention name(s): ciprofloxacin
Intervention type(s): Drug
Intervention description(s): ciprofloxacin 200mg tablet (single dose)
Intervention MeSH terms: Ciprofloxacin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: ciprofloxacin; pharmacokinetics; formulation