To enhance patient compliance and treatment efficiency, several investigators have focused on developing novel routes of drug
delivery or reducing the multiple dosing regimens to once-daily products in the form of controlled-release formulations (1).
In vitro release studies using conventional and modified dissolution methods can provide insight into the performance of drug-delivery
systems, and radionuclides incorporated into the dosage form provide information on the in vivo behavior of dosage forms. Gamma scintigraphy is a well-established radionuclide imaging technique (2). This technique is
valuable for evaluating various dosage forms. It is noninvasive and provides reliable information on the transit time of dosage
forms in different regions of the gastrointestinal (GI) tract and various other body organs. Gamma scintigraphy can analyze
the time taken for disintegration of the drug product and the site where disintegration occurs. The effect of different conditions
such as the presence of food, diseased state, and dosage size also can be explored. In current experimental protocols, it
is common to evaluate the in vivo performance of drug-delivery systems in healthy volunteers or patients using this imaging technique (3). The process is significantly
different from traditional techniques such as diagnostic X-ray methods where external radiation is passed through the body
to form an image (4). Contrary to this approach, the gamma scintigraphic technique relies on the detection of radiation emitted
from radionuclides tagged with dosage forms that are administered intravenously or orally. Release of the tagged tracer is
monitored rigorously in vitro. Moreover, this technique should be performed in a protected environment (1).
Gamma scintigraphy
In gamma scintigraphy, nuclear imaging is generally carried out with planar or single photon emission computed tomography
(SPECT) cameras capable of detecting the incorporated radionuclides that emit gamma radiation with energies between 100 and
250 KeV (5). Emitted radiations are further captured by external detectors such as gamma cameras. The following are advantages
of gamma scintigraphy:
- Very little radiation exposure to the participating subjects compared with roentgenography (i.e., X-ray methods)
- Qualitative, as well as quantitative, observations that can be recorded that are not feasible with other techniques
- Totally noninvasive
-
In vivo evaluation of dosage forms is possible under normal physiological conditions.
Radiolabeling of dosage forms
Table I: Properties of commonly used radionuclides.
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Before imaging by this technique, the dosage form should be radiolabeled. Radiopharmaceuticals labeled with 99mTc are most commonly used; however, other sources of radionuclides that can be used in traditional gamma scintigraphy are
81mKr, 111In, 123I, and 131I (6, 7). Table I represents half-life and the types of emitted radiation of these radionuclides. A suitable radionuclide
for scintigraphic studies is selected by considering the following factors (8):
- Radiation energy of gamma rays should be within the detection range of the gamma camera
- Emitted radiation well-suited for in vivo applications
- The half-life of the radionuclide must be adapted to the period of testing
- The tracer should not alter the performance of dosage forms being investigated
- Cost and availability.
The radionuclide is incorporated into the formulation using an appropriate radiolabeling technique, so it can act as a marker
for a particular event. Usually, dosage forms are assessed to determine the release of a drug, but in some cases, the radionuclide
is required to be retained in the formulation to investigate the ultimate fate of the dosage form in terms of site, rate,
and extent of drug absorption. The observed transit of the dosage form also can be correlated with the rate and extent of
drug absorption (9).
