ActiPix SDI300 Surface Dissolution Imaging System

Transcription

1 Product Note: PN002B Figure 1. SDI300 Surface Dissolution Imaging System 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), tablets, formulations, gels, liquids, suspensions, stents and patches. Used as a tool for accelerated pre-formulation 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 microns to millimetres from the surface, the key distance range for understanding dissolution. It 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. 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 Paraytec Ltd

2 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 of a chosen wavelength 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 and tablets. The small volume cell allows fast analysis for sparingly soluble compounds. Powerful software for detailed interrogation The SDI300 includes automated software for direct visualisation and analysis of the dissolution process. The software 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. Figure 3. SDI300 dissolution imaging cell Figure 2. ActiPix sensor head fitted with dissolution imaging cell Figure 4. ActiPix dissolution application As a pharmaceutical research lab engaged in formulation design and development, we are constantly looking at new ways to study and understand drug release and dissolution processes. The SDI300 allows detection of drug release/dissolution a few hundred microns from the surface of a wide variety of samples such as active pharmaceutical ingredients, suspensions, gels, and stents. We are impressed with the ability to monitor the formation of concentration gradients in real time along with the possibility of performing quantitative measurements as a function of both time and distance. The SDI300 is a flexible, easy to use, multipurpose UV imaging tool highly suited for investigating drug transport processes such as dissolution and release, at a level of detail that we could not previously achieve. Jesper Østergaard (Associate Professor) Faculty of Pharmaceutical Sciences University of Copenhagen, Denmark 2

3 Product Note: PN002B Intrinsic dissolution rate (IDR) Close to the surface, the velocity in the flow direction, v X, increases linearly with the distance perpendicular to the surface, z. The dependence of concentration on x and z has the form shown in Figure 5. Each line is a contour of constant concentration. API dissolution (z) is balanced with a horizontal flow stream (v x ). Thus for a given z distance from the surface, a rapidly dissolving API will require a higher volumetric flow to reach the same steady state concentration as a slowly dissolving API. Figure 5. Intrinsic dissolution rate (IDR) measurement 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 is cored out of the whole tablet and placed in the formulations holder. This enables 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. The blue bar represents the region across the centre of the sample. The green bar represents the downstream region after the edge of the sample. The orange bar represents the area used to calculate IDR. In this study, the IDR was calculated to be 4.1 µg/min/cm 2 at ~25 C. Note the literature value using the rotating disk method is 2.2 µg/min/cm 2 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 on the next page. Area used to calculate surface IDR Surface dissolution at centre of sample Post sample region Top surface of griseofulvin pellet Figure 6. Griseofulvin IDR study 3

4 Rapid packing of APIs N.B. Concentrations at maxima are > 10x higher than expected from solubility Figure 7. Absorbance profile Absorbance is converted to concentration knowing the molar absorption coefficient at the wavelength used (14 x 10 3 M -1 cm -1 at 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. Figure 8. Formulation packing tool An optional formulation packing tool (shown above), 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. 4

5 Product Note: PN002B Controller Light source Wavelengths Filter bandpass Caffeine limit of quantification Baseline noise Specification Pulsed xenon lamp, nominal rate 3 Hz nm, filter selectable 10 nm 1 ppm (5 µm) to 250 ppm (1.3 mm) at 254nm 3 mau RMS Imager properties Spatial resolution 14 µm x 14 µm 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 cm 3 Area of flow cell cm 2 Cell Path length 3 mm Temperature range (optional) ambient to 40 C Sample types compressed powders, liquids, gels, stents, solid suspensions 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 PC High specification desktop PC with 22" monitor (includes software) Power 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 ºC 5

6 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 nm filter 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. Manufactured by: Paraytec Ltd. 1a St George s Place, Tadcaster Road YORK, YO24 1GN, UK Tel: +44 (0) Fax: +44 (0) Enquiries: info@paraytec.com Sales: sales@paraytec.com For more information on the ActiPix SDI300, please go to