This document discusses Biopharmaceutics & Drug Disposition, a journal that publishes articles relating to drug discovery, development, and therapeutic use. It focuses on pre-clinical and clinical studies of drug absorption, distribution, metabolism, and excretion. The journal excludes simple bioavailability studies without mechanistic interpretation or analytical methods. It also investigates drugs for manufacturers, developing testing methods and examining drugs according to good manufacturing practice standards. An example is provided of a study on the variable bioavailability of the tuberculosis drug rifampicin from different dosage forms.

1. BY ALBUISSA MUHAMMED HAMED
4th course
2016-2017

2. Description
Biopharmaceutics & Drug Disposition publishes original
review articles, short communications, and reports in
biopharmaceutics, drug disposition, pharmacokinetics
and pharmacodynamics, especially those that have a direct
relation to the drug discovery/development and the
therapeutic use of drugs.
These includes:
· animal and human pharmacological studies that focus on
therapeutic response. pharmacodynamics, and toxicity
related to plasma and tissue concentrations of drugs and
their metabolites

3. · in vitro and in vivo drug absorption, distribution, metabolism,
transport, and excretion studies that facilitate investigations related
to the use of drugs in man
· studies on membrane transport and enzymes, including their
regulation and the impact of pharmacogenomics on drug absorption
and disposition,
· simulation and modeling in drug discovery and development
· theoretical treatises
· includes themed issues and reviews
The journal excludes manuscripts on
· bioavailability studies reporting only on simple PK parameters such
as Cmax, tmax and t1/2 without mechanistic interpretation
· analytical methods
Reports must contain current citation of the literature and convey
new information.
Biopharmaceutics & Drug Disposition is one of the top accessed and
cited journals in the field, as a result of the high quality papers
published in the journal, and is marketed by Wiley across the world.

4. INVESTIGATION OF DRUGS FOR MANUFACTURERS
MICROMUN can be commissioned by pharmaceutical
manufacturers to develop test methods and to investigate drugs
according to GMP. MICROMUN applies cell biological-, molecular
biological-, immuno chemical- and biochemical methods for this
purpose. MICROMUN provides methods to determine the infective
virus burden in drugs which are derived from biological sources. A
broad spectrum of animal- and human pathogenic viruses can be
screened.
MICROMUN has developed assays for the determination of the
identity of drugs and vaccines by molecular biological- as well as by
immunological methods.
MICROMUN carries out quantitative and qualitative determinations
of nucleic acid- and protein content of drugs and biological samples.
Drug preparations are quantitatively inspected for the presence of
bacterial endotoxins with the aid of the LAL assay according to the

5. Implication of biopharmaceutics and
pharmacokinetics of rifampicin in variable
bioavailability from solid oral dosage forms.
Rifampicin is one of the oldest and most effective chemotherapeutic
agents available for the treatment of tuberculosis but exhibits
variable bioavailability from separate and fixed dose combination
formulations, which has been identified as a major bottleneck in the
effective treatment of tuberculosis. In this investigation, physico-
chemical characterization, single dose pharmacokinetic studies and
the permeability of rifampicin under physiological conditions in the
rat were studied to trace the possible reasons for its variable
absorption. Rifampicin exhibits very high solubility in acidic and
basic pH, corresponding to the pH of the stomach and distal
intestine, respectively, whereas it is moderately soluble at the jejunal
pH. From single-dose pharmacokinetic studies and permeability
characterization, rifampicin is a highly permeable molecule and
thus according to BCS, it

6. is a borderline class II drug. This investigation has ruled out the
possibility of intrinsic solubility, effective permeability, drug
decomposition, presystemic metabolism and interaction with other
antituberculosis drugs as direct factors responsible for the variable
bioavailability of rifampicin. However, it was found that the rate of
dissolution in association with pH and the concentration-
dependent absorption of rifampicin affects the in vivo performance
of the dosage forms. In addition, this is the first report of
methodology for correcting inlet concentration for permeability
calculations of a chemically unstable molecule.
The United States Food and Drug
Administration's Investigational New Drug (IND) program is the
means by which a pharmaceutical company obtains permission to
ship an experimental drug across state lines (usually to clinical
investigators) before a marketing application for the drug has been
approved. The FDA reviews the IND application for safety to assure
that research subjects will not be subjected to unreasonable risk. If
the application is cleared, the candidate drug usually enters a Phase

7. Application contents
The IND application must contain information in three broad
areas:[1]
Animal Pharmacology and Toxicology Studies – Preclinical data to
permit an assessment as to whether the product is reasonably safe
for initial testing in humans. Also included are any previous
experience with the drug in humans (often foreign use).
Chemistry and Manufacturing Information – Information pertaining
to the chemical composition, manufacturing methods, stability, and
controls used for manufacturing the drug substance and the drug
product. The chemical stability and activity of the product must also
have been tested. This information is assessed to ensure that the
company can adequately produce and supply consistent and active
batches of the drug.
Clinical Protocols and Investigator Information – Detailed protocols
for proposed clinical studies to assess whether the initial-phase trials
will expose the subjects to unnecessary risks. enrolled.

8. Information on the qualifications of clinical investigators—
professionals (generally physicians) who oversee the administration
of the experimental compound—to assess whether they are
qualified to fulfill their clinical trial duties. Finally, commitments to
obtain informed consent from the research subjects, to obtain
review of the study by an institutional review board (IRB), and to
adhere to the investigational new drug regulations.
An IND must also include an Investigator's Brochure which is a
document intended to educate the trial investigators of the
significant facts about the trial drug they need to know to conduct
their clinical trial with the least hazard to the subjects or patients
who will be

9. IND types
There are three IND types:[1]
An Investigator IND is submitted by a physician who both initiates
and conducts an investigation, and under whose immediate
direction the investigational drug is administered or dispensed. A
physician might submit a research IND to propose studying an
unapproved drug, or an approved product for a new indication or in
a new patient population.
Emergency Use IND allows the FDA to authorize use of an
experimental drug in an emergency situation that does not allow
time for submission of an IND.
Treatment IND is submitted for experimental drugs showing
promise in clinical testing for serious or immediately life-
threatening conditions while the final clinical work is conducted
and the FDA review takes place.

10. Additional regulations
Experimental drugs under an IND must be labeled, "Caution: New
Drug – Limited by Federal (or United States) law to investigational
use.
Noteworthy examples
The FDA runs a medical marijuana IND program
(the Compassionate Investigational New Drug program). It stopped
accepting new patients in 1992 after public health authorities
concluded there was no scientific value to it, and due to
President George H.W. Bush administration's desire to "get tough on
crime and drugs." As of 2011, four patients continue to
receive cannabis from the government under the program.[2]

14. ALBUISSA MUHAMMED HAMED
887B
4th course