Table 1 Imaging modalities available to visualise oral dosage forms in the body

Gamma scintigraphy

• It is possible to determine both disintegration of the formulation and drug release using this method [27].

• Useful to identify the location of the dosage form within a body mass [27].

• Limited topographic information obtained and the use of radioactive materials [28, 29].

• Radiation involved reduces the number of scans a subject can safely undergo, and restricts its use in women and children [25].

• Wilding et al. [27] reviewed the role of gamma-scintigraphy in the visualisation of oral drug delivery.

• Teran and colleagues [30] described the dissolution and disintegration profiles of different drug models depending on the radiotracer chosen.

Magnetic Resonance Imaging

• This type of imaging allows high resolution structural images of the desired area to be obtained [19, 31] with high scan volumes [32].

• No radiation exposure [31]. The avoidance of ionising radiation is an important advantage allowing for the possibility of rapid repeated measurements to observe changes following in-vivo administration of dosage forms [33]

• Contrast agents can be incorporated in to the oral dosage form to improve the quality of images. Contrast agents can be either positive or negative in their enhancement and allow for oral dosage forms to be distinguished from food or gas bubbles [32].

• The gastrointestinal tract is highly mobile, and tidal breathing results in movement of the abdominal contents, which can lead to the generation of artefacts on MRI images. Although there are simple solutions to get around this issue [34, 20].

• It can be difficult in a fed state to differentiate the formulation from food and gas bubbles [20]. In addition, participants in the fasted state will have very little water in the stomach and small intestine which may lead to poor imaging of the dosage form possibly altering the dissolution rate [20].

• Reviewed by Richardson [24] for the potential for its use to visualise dosage behaviour in-vivo .

• MRI used to visualise the formation of the carbonated alginate raft that is formed with the anti-reflux product Gaviscon® [17].

• Liquid emulsions have also been investigated in the stomach using MRI [16].

• Feasibility study that has investigated, with success, the ability to use MRI to compare different dosage formulations of a drug [23].

Computed Tomography and X-rays

• Imaging using radio-opaque substances is able to identify the position of formulations following oral administration.

• Radio-opaque substances are typically needed for imaging with barium sulphate often used once incorporated into the dosage form [35,36,37], however limited detail of the surrounding soft tissue anatomy is provided.

• High contrast resolution images come with a drawback of requiring greater doses of radiation [38]. This reduces the number of scans that can be performed on a single subject.

• Dissolution of tablets was described by Vemula et al. [36] however the detail was limited, and the time course of data acquisition was over several hours at set time intervals, until the tablet was no longer seen.

• Lai and colleagues [28] performed a study where they used a combination of single-photon emission computed tomography/computed tomography (SPECT/CT) to visualise the movement of a colon targeting dosage forms from administration to site of release [28]. SPECT/CT was able to show disintegration of the tablet and the position in the GIT at which this was occurring [28].

Ultrasound

• US uses relatively affordable and portable US machines, increasing accessibility, whilst providing real time acquisition [39].

• Limited applicability in pharmaceutical dosage form evaluation, as detection of dosage forms following oral administration can be difficult due to the presence of food or lack of water [40] which can make identification of the dosage form difficult.

• The presence of gas in the GIT acts as an effective reflector of US waves, making quality images difficult to obtain and the visualisation of behaviour of the dosage form difficult [32].

• US has been explored as an avenue for in-vivo imaging of oral dosage forms to visualise ingested medications in acute poisoning cases [40]. However, the results from this study highlight the unreliable images generated through US imaging of oral dosage forms in-vivo [40]

• US does have utility in some areas of pharmaceutical imaging due to its ability to distinguish between the small intestine and the colon. Kobayashi [41] presented a case study where US was successfully used to detect the location of the patency capsule in a patient who was evaluated to be at risk of capsule retention in capsule endoscopy

Magnetic Moment Imaging

• MMI provides high resolution images both in temporal and spatial dimensions [26], allowing for tracking of dosage forms through the GIT.

• This method also has the advantage of its ability to image real time movements of the dosage forms [25].

• Large costs associated with running and maintaining the equipment, and the special requirement that they be housed in a magnetically shielded environment [19, 25].

• Goodman and colleagues showed how the fed state significantly effecting onset and time course of disintegration and the ability to show real time movement of the dosage form [25]