Paraytec Ltd

Introduction

The ActiPix™ SDI300 is a powerful UV area imaging system which enables quantitative imaging of surface phenomena for a diverse range of substances including active pharmaceutical ingredients (APIs), formulations, gels, liquids, suspensions, stents and patches.

Used as a tool for accelerated pre-formulations development, the SDI300 is proven to enable intrinsic dissolution rates to be obtained in less than 20 minutes, a fraction of the time compared to conventional dissolution systems. The dissolution medium can easily be exchanged, e.g. from 0.1 M HCl to a neutral buffer or to an aqueous alcoholic solution.

Compact in design, the SDI300 system includes award-winning ActiPix™ UV area imaging technology, a surface dissolution imaging sample holder, an integrated syringe pump, and software which enables real time quantitative recording and review of data. The SDI300 uses a highly sensitive UV area imaging sensor to record, interrogate and analyse a variety of complex processes. 

The ActiPix™ SDI300 also provides unique insights into processes taking place from microns to millimetres from the surface, the key distance range for understanding dissolution, and enables both erosion and dissolution to be visualized simultaneously.

The optimum wavelength can be selected to allow sensitive and selective monitoring of the substance of interest.

The ActiPix™ SDI300 is the first tool of its kind to offer quantitative and mechanistic information for a variety of applications.

Powerful software for detailed interrogation

The SDI300 includes automated software for direct visualisation and analysis of the dissolution process. It has been designed for ease of use, with integrated detector and pump control, automated calibration and advanced image processing algorithms. Dissolution rates can be determined in around 20 minutes, significantly faster than other techniques. The data files are recorded, enabling visualisation and recording of the total surface dissolution processes. This aids the user to gain a better understanding of the mechanistic processes involved in dissolution.

Ideal compounds for use with the SDI300

The SDI300 is ideal for use with sparingly soluble APIs. The IDR of the API can be measured in around 20 minutes. The API can be analysed as a pure powder or formulated with excipients in solids, suspensions, gels or liquids. When present in solid dosage forms, a small sample can be cored out of the whole tablet and placed in the formulations holder. This will enable rapid interrogation of the effectiveness of the formulated mix.

Example data: griseofulvin IDR study

Figure 6 below shows typical data obtained by the SDI300. Three separate regions are used for measurement.

· Blue line represents the region across the centre of the sample.

· Green line represents the downstream region after the edge of the sample.

· Orange bar represents the area used to calculate IDR.

In this study, the IDR was calculated to be 4.1 µg/min/cm2 at ~25°C. Note the literature value using the rotating disk method is 2.2 µg/min/cm2 at 37°C.

Since the SDI300 probes dissolution directly into the small volume by the surface, rather than into large volumes typical of standard dissolution equipment, results for sparingly soluble APIs can be obtained much faster than with conventional systems. Additionally, detailed information on the dissolution process not available by other techniques (surface concentration, thickness of the diffusion layer) is obtained by the SDI300 as shown in Figure 7.

Operation

An integrated high precision pump drives a 20 mL syringe filled with the appropriate dissolution medium. This syringe connects to the SDI300 imaging cartridge located inside the remote sensor head. The dissolution medium is pushed to fill the flow chamber within this cartridge and background readings are taken. The cartridge is then packed with the sample of interest and secured into the remote sensor head. The dissolution medium is then re-introduced into the flow chamber. The SDI300 software records the surface dissolution process.

The data can then be processed for measurement of the intrinsic dissolution rate (IDR) of the  API  - the whole process typically takes around 20 minutes.  Additional mechanistic information such as expansion of the formulation, particle release and downstream dissolution may be obtained by directly viewing the volumes immediately above the surface as well as downstream.

Patented UV imager

Paraytec’s patented self-referencing ActiPix™ technology is used to capture, record and quantify the surface dissolution process. The sample is held in place using a custom cell holder. Filtered light is shone from above the sample holder. A 9 mm x 7 mm UV chip, with 7 x 7 µm pixel resolution, captures the images and  the processed data is transformed into absorbance movies which are stored on a PC.

Flexible imaging cell

At the heart of the SDI300 is Paraytec’s surface dissolution imaging cell (patent pending). The cell has been designed to handle a variety of materials, e.g. powders, stents, gels and liquids, suspensions. The small volume cell allows fast analysis for poorly soluble compounds.

Absorbance is converted to concentration knowing the molar absorption coefficient at the wavelength used (14 x 10 3 M-1 cm-1at 280 nm) and the sample width at the centre (0.2 cm). The calculated concentration, 0.3 mM, is of an order of magnitude greater than the literature value for solubility (0.03 mM at 37 °C, 0.01 M at 25 °C).

The distance for the concentration to decrease to half its value at the surface is 0.1 mm.  This is far lower than that expected based on the diffusion coefficient of the monomer. All data suggests griseofulvin dissolves from the surface as aggregates, initially forming a supersaturated solution.

Rapid packing of APIs

An optional 3-piece formulation packing tool (shown below), complete with packing tubes, is available to ensure batch to batch reproducibility.

Temperature control

An optional temperature control module may be connected to enable measurement at physiological temperatures.

Other application opportunities

The SDI300 may also be applied to other areas where surface measurement of UV active species is important, such as monitoring protein adsorption on contact lenses and monitoring the effectiveness of materials to reduce dental erosion.

Specification

Controller

Light source                                                       Pulsed xenon lamp, nominal rate 3 Hz

Wavelengths                                                      200-600 nm, filter selectable

Filter bandpass                                                  10 nm

Caffeine limit of quantification                            1 ppm (5 µM) to 250 ppm (1.3 mM) at 254nm

Baseline noise                                                   3 mAU RMS

Imager properties

Pixel size 7 x 7 µm

Imager area 9 x 7 mm (W x H)

Remote sensor head size 6 x 6.5 x 11 cm (H x W x L)

Flow cell holder

Round sample holder 2 mm ID

Rectangular sample holder 5 x 1.8 mm

Volume of flow cell 0.063 cm3

Area of flow cell 0.031 cm2

Cell Path length 3 mm

Temperature range (optional) ambient to 40 °C

Sample types compressed powders, liquids, gels, stents, solid sus- pensions

Pump

Flow rate of integrated pump 0.01 µL/hr (10 µL syringe) to 45 mL/min (60ml syringe)

Dissolution media options aqueous (e.g. 0.1 N HCl) to non-aqueous (e.g. ethanol)

pH range pH 1.2 – 10.0

PC

High specification desktop PC with 22 " monitor

(includes software)

Power

110 – 240 V AC 50/60 Hz

(4) receptacles required as below:

(1) controller, (1) pump, (1) monitor, (1) PC

Bench space required

1 m x 1 m

Environment

15 – 30 ºC

Ordering information

Part number:

SDI300

Description:

Surface Dissolution Imaging System

ActiPix™ D100

Remote sensor head

Low volume syringe pump

High performance desktop PC with 22" monitor

Dissolution imaging cartridge

Upright dissolution sensor stand

254, 280 and 214 nm filters

Tool kit

ActiPix™ SDI300 application  software (MS Windows XP/Vista 32-bit compatible):

• Visualisation and dissolution analysis
• Real time data capture and imaging
• Integrated detector control via USB
• RS232 pump control
• Post processing image analysis tools
• Data exporting

Price on application.

Please order separately:

• Formulation press (p.n. SDIPRESS) with packing tubes (p.n. SDITUBES)
• Temperature control module (p.n. SDITCONT)

Contact your local distributor and request further details.