Copley Scientific, sejak 1946, jadi rujukan dunia untuk alat uji farmasi—dari inhalasi hingga sediaan topikal. Independen, inovatif, dan konsisten dalam kualitas global.
Driving Results in Pharmaceutical Testing
TABLETS & CAPSULES • SUPPOSITORIES • TRANSDERMALS POWDERS & GRANULES • SEMISOLIDS
2020 EDITION
About Us
Copley: Driving Results for Over 70 Years Founded in 1946 in Nottingham, UK, Copley remains family owned and managed. We are recognised as the world’s leading manufacturer of inhaler test equipment, in addition to being a trusted provider of test instrumentation for other pharmaceutical dosage forms.
We continue to work closely with industry groups and leading experts to bring relevant new products to market, with all equipment backed by expert training and lifetime support. Committed to excellence, we aim to deliver exemplary service for an outstanding customer experience. We deliver pharmaceutical testing equipment with the necessary accuracy and reproducibility hard-wired into its design by adopting the same Quality by Design (QbD) principles that our customers rely on to control product performance. Continuous improvement is a core element of this approach and we strive to exceed the expectations of the industry, not only by enhancing equipment performance but also through unrivalled service.
These commitments are exemplified by our investment in the ISO 9001:2015 Quality Management System for which we have certification to the latest standard for all aspects of our business, including equipment design. Copley customers benefit from: • High quality pharmaceutical testing equipment, designed, manufactured and tested in the UK • Product lifetime support from our friendly and
experienced technical support team • First-class training and education
Copyright
This edition of the Copley Scientific Limited brochure is copyright 2020. All rights reserved. No portion of this brochure may be reproduced without the permission of Copley Scientific Limited. Copley Scientific Limited reserves the right to make changes without notice to any products herein to improve reliability or design.
Copley Scientific Limited does not assume any liability arising out of the application or use of any product described herein. Neither does it convey any licence under its patent rights nor the rights of others. Any third party documentation or organisation mentioned herein is referential only and implies no company or product endorsement from, or affiliation with, Copley Scientific Limited.
2
About us
The Copley Promise
Compliant Products are certified to quality standards defined by global pharmacopoeias and regulators, ensuring data integrity. Innovative product design features ensure ease-of-use and maximum productivity by streamlining work flows. Innovative
Trusted
Robust design and manufacture from a company with over 70 years’ experience guarantees product reliability and longevity.
3
Pharmaceutical Testing
Contents
Hardness
50
Choose your DISi System Accessories 32 Baskets, Paddles and Rotating Cylinders 32 Vessels 33
About Us
2
Background: Hardness Testing
50
ISO 9001: 2015 Quality Management System The Copley Promise
51
Test Apparatus & Method
2 3
Hardness Testers
52 52 53 54 54 55 55 56 57 58 58 59 59 59
EMC Ultra-Precision Dissolution Vessels
TBF 100i
Table of Contents
4
33 33 34 34 35
TBF 100i: Key Features
Vessel Covers
TBF 100i: Touchscreen User Interface
Classification of Medicines
6
Automatic Tablet Drop
Key Features
Sampling Probes
Reporting
Equipment Selection Guide
7
Performance Verification Testing
Compliance & Maintenance
DISi Series: Qualification & Maintenance
Choose your Tablet Hardness Tester TBF 100i Technical Specifications Choose your TBF 100i Accessories
Organisations and their Roles
8
36 36
DISi Series: Qualification Tools
Disintegration
12
Hygiene: Anti-Bacterial/ Algae Treatment
Tablet Weight & Thickness
36
Background: Disintegration Testing
12 13
Tablet Hardness Tester: TH3
Test Apparatus & Method
Special Applications
37 37 37 37 37 38 38 39 39
TH3: Key Highlights
Transdermal Patch Testing
Disintegration Testers: DTGi Series
14
Reporting
Paddle Over Disk Watch Glass/Patch Rotating Cylinder Intrinsic Dissolution
DTGi Series: Key Features 15 DTGi Series: Touchscreen User Interface 16 Key Features 16 Reporting 17 Compliance & Maintenance 17 Choose your DTGi Disintegration System 18 DTG 100i 18 DTG 200i 18 DTG 300i 18 DTG 400i 19 DTG 200i-IS 19 DTGi Series: Technical Specifications 20 Temperature Calibration 20 Choose your DTGi System Accessories 21 Standard Accessories 21 Accessories for Specialist Dosage Forms 21 Dissolution 22 Background: Dissolution Testing 22 Test Apparatus & Method 24 Pharmacopoeial Requirements 24 United States Pharmacopeia (USP) 24 European Pharmacopoeia (Ph.Eur.) 24 Dissolution Testers DISi Series 26 DISi Series: Key Features 27 DISi Series: Touchscreen User Interface 28 Key Features 28 Reporting 29 Compliance & Maintenance 29 Choose your DISi Dissolution System 30 DIS 600i 30 DIS 800i 30 DISi Series: Technical Specifications 31 Temperature Calibration 31
Powders
60
Background: Powders Powders: Flowability Flow Through an Orifice
60 61 61 62 62
Small Volumes Special Baskets
Basket for Suppository Dissolution
Angle of Repose
Shear Cell Attachment
Friability
40
Powders: Bulk and Tapped Density
63
Compressibility Index and Hausner Ratio
Background: Friability Testing Test Apparatus & Method
40
63
41
Powders: Flowability Testers BEP2 with Cylinder Attachment BEP2 with Funnel Attachment BEP2 with Funnel and Shear Cell Attachment BEP2 with Funnel and Angle of Repose Attachments
64 64 64
Friability Testers
42 42 43 44 44 45 45 46
FRVi Series
FRVi Series: Key Features FRVi Series: Touchscreen User Interface
65
Key Features
65
Reporting
Compliance & Maintenance Choose your Friability System
Powders: Bulk Density Tester
67
Powders: Tapped Density Testers
68
FRVi Series: Friability Calculator 46 FRVi Series: Friability & Abrasion Drums 47 FRVi Series: Technical Specifications 47 Friabimat SA-400 48 Friabimat SA-400: Key Highlights 48 Friabimat SA-400: Technical Specifications 49
JVi Series: Key Features 69 JVi Series: Touchscreen User Interface 70 Reporting 71 Compliance & Maintenance 71 Choose your JVi Tapped Density System 72 JVi Series: Technical Specifications 73
4
Contents
Semisolids
74
Background: Semisolids Testing
74 75
Test Apparatus & Method
Vertical Diffusion Cell System: HDT 1000
76 77 78 78
HDT 1000: Key Features
Choose your HDT Series System
HDT 1000
HDT 1 78 Choose your HDT System Accessories 79 Cells 80 Cell Specification 80 Type B 80 Type C 80 Skin Cell 80 Membranes 81 PVDF 81 Supor Polyethersulfone 81 Strat-M Membranes 81 Degassing (Vacuum Deaeration Apparatus Model - VDA) 82 Immersion Cell 83
DTG 400i
Suppositories
84
Background: Suppository Testing
84 85 86 87 88
Test Method & Apparatus
Suppository Tester: SDT 1000 SDT 1000: Key Features Softening Time Attachment
Vaginal Tablet Tester (VTT)
89
Friabimat SA-400
Thickness
90
Background: Thickness Testing
90
91
Test Method & Apparatus
Calipers & Thickness Testers Digital Caliper Model 500 Tablet Thickness Tester 700 Tablet Thickness Tester 547
92 92 92 92 92
Digimatic Mini Processor Model 264
Choose your Thickness Tester
93
Services
94
95 96 96 97 97
Design
Servicing IQ/OQ/PQ
HDT 1000
Training Support
Index
98
5
Pharmaceutical Testing
Classification of Medicines Introduction
One of the clearest taxonomic guides for the classification of pharmaceutical dosage forms is to be found in Chapter <1151> of the US Pharmacopeia (USP) entitled “Pharmaceutical Dosage Forms”. The guide is depicted in “Figure 1. Compendial taxonomy for pharmaceutical dosage forms”, a modified version of which appears below.
This proposes a three tier system with the first tier being based on the region of the body to which the drug is to be administered, i.e. gastrointestinal (oral), mucosal membrane (rectal, vaginal, oropharyngeal, ophthalmic, otic and urethal), skin surface (topical, transdermal), injection including implants (parenteral) or nasal/lungs (pulmonary). The second tier describes the dosage form concerned, e.g. tablet, capsule, suppository, cream, ointment, transdermal patch, injection, inhaler, etc., whilst the third tier describes whether the dosage form concerned is designed for immediate, extended or delayed release. It is the first tier classification which has been used as the basis for the Equipment Selection Guide to be found on page 7. This lists the route of administration, the dosage form and test parameter concerned, the chapter relating to that test parameter in both European and US Pharmacopoeia (where applicable) and, in the final column, the page number in this catalogue where a description of the relevant test instrumentation can be found.
TIER 1
Route of Administration
GASTROINTESTINAL / MUCOSAL / INHALATION / INJECTION / TOPICAL (DERMAL)
TIER 2
Dosage Form
AEROSOLS / CAPSULES / CREAMS / EMULSIONS / FILMS / FOAMS / GASES GELS / GRANULES / GUMS / IMPLANTS / INJECTIONS / INSERTS / IRRIGATIONS LIQUIDS / LOZENGES / OINTMENTS / PASTES / PELLETS / PILLS / PLASTERS POWDERS / SOAPS / SHAMPOOS / SOLUTIONS / SPRAYS / STRIPS SUPPOSITORIES / SUSPENSIONS / SYSTEMS / TABLETS / TAPES
TIER 3
Release Pattern
IMMEDIATE / EXTENDED / DELAYED
6
Classification of Medicines
Equipment Selection Guide
European Pharmacopoeia
United States Pharmacopeia
Page No. (in this brochure)
Route of Administration - Dosage Form
GASTROINTESTINAL Tablets & Capsules - Disintegration
Chapter 2.9.1
Chapter 701
Pages 14-21
GASTROINTESTINAL Tablets & Capsules - Dissolution
Chapter 2.9.3
Chapter 711
Pages 26-39
GASTROINTESTINAL Tablets & Capsules - Friability
Chapter 2.9.7
Chapter 1216
Pages 42-47
GASTROINTESTINAL Tablets & Capsules - Breaking Force
Chapter 2.9.8
Chapter 1217
Pages 52-59
GASTROINTESTINAL Tablets & Capsules - Weight & Thickness
Chapter 2.9.5
Chapter 905
Pages 58
GASTROINTESTINAL Powders - Bulk & Tapped Density
Chapter 2.9.34
Chapter 616
Pages 67-73
GASTROINTESTINAL Powders - Flowability
Chapter 2.9.16 & 2.9.36
Chapter 1174
Pages 64-65
GASTROINTESTINAL Granules & Pellets - Friability
Chapter 2.9.41
---
Pages 48-49
MUCOSAL MEMBRANE Rectal - Drug Release
Chapter 2.9.2
Chapter 1004
Pages 86-89
MUCOSAL MEMBRANE Oropharyngeal, Opthalmic, Otic & Urethal
Outside the scope of this brochure
MUCOSAL MEMBRANE Vaginal - Drug Release
Chapter 2.9.22
---
Pages 89
SKIN SURFACE - Semisolids Drug Release - Permeation
---
Chapter 1724
Pages 76-83
SKIN SURFACE Transdermal Patches - Drug Release
Chapter 2.9.4
Chapter 724
Pages 37
INJECTION Injections & Implants
Outside the scope of this brochure
LUNGS Inhalers
See: Inhaler Testing Brochure
Chapter 2.9.18 & 0671
Chapter 601
LUNGS Nebulisers
See: Inhaler Testing Brochure
Chapter 2.9.44
Chapter 1601
NASAL Inhalers & Sprays
See: Inhaler Testing Brochure
Chapter 2.9.18 & 0676
Chapter 601
7
Pharmaceutical Testing
Organisations and their Roles
Introduction The ultimate responsibility for the safety, quality and efficacy of medicines and medical devices lies with the various national regulatory bodies designated to
safeguard public health. In Europe, Japan and in the USA this function is performed by the European Medicines Agency (EMA) , the Ministry of Health , Welfare and Labor (MHWL) and the Food and Drug Administration (FDA) respectively. The regulatory authorities are supported in this role by the Pharmacopoeias whose job is to define the standards with which the drug formulation shall comply and the methods by which compliance will be adjudged. In October 1999, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)* published a single set of global specifications covering the Test Procedures and Acceptance Criteria for new drug substances and products . The guidance takes the form of a number of universal tests/criteria considered generally applicable to: a) new drug substances and b) new drug products together with a number of additional tests and acceptance criteria for specific substances and dosage forms, including solid oral drug products, liquid oral drug products and parenterals.
approach to pharmaceutical manufacturing. This initiative gave birth to Process Analytical Technology (PAT) , a framework for understanding and improving the processes involved in pharmaceutical development, manufacturing and quality control, described in FDA’s Guidance of September 2004. PAT operates on the premise that quality cannot be tested into products; rather, it should be built-in or by design. The goal is to ensure final product quality by understanding and controlling the processes involved in the manufacturing operation.
The additional tests for tablets (coated and uncoated) and hard capsules, for example, include: a) Dissolution b) Disintegration c) Hardness/Friability d) Uniformity of dosage units e) Water content and f) Microbial limits The guideline on quality concerned (Q6A) was subsequently agreed and adopted by all of the parties involved, including the EMA, FDA and MHWL. In 2002 the FDA launched a new initiative “Pharmaceutical cGMPs for the 21st Century” in which it proposed a new risk-based
* See Page 9 for further details
ICH Quality Guidelines Q1A - Q1F Stability
Q8 - Pharmaceutical Development
Q2 - Analytical Validation
Q9 - Quality Risk Management
Q3A - Q3D Impurities
Q10 - Pharmaceutical Quality System
Q4 - Q4B Pharmacopoeias
Q11 - Development and Manufacture of Drug Substances
Q5A - Q5E Quality of Biotechnological Products
Q12 - Lifecycle Management
Q6A - Q6B Specifications
Q13 - Continuous Manufacturing
Q7 - Good Manufacturing Practice
Q14 - Analytical Procedure Development
8
Organisations and their Roles
The Quality by Design (QbD) approach agreed and now adopted by the EMA, FDA and the Japanese MWHL in the form of the five quality related guidelines, ICH Q8 to Q12, extends this philosophy to all parts of the product life cycle from product development, transfer through to manufacturing, manufacturing and finally product end. ICH Q8 Pharmaceutical Development describes the suggested contents of a regulatory submission based on the QbD format. ICH Q9 details a systematic approach to quality risk management, whilst ICH Q10 describes a new quality management system based on the complete product life cycle and referred to as the Pharmaceutical Quality System. ICH Q11 provides a Guideline to the “Development and Manufacture of Drug Substances”, including the type and extent of information to be submitted in regulatory dossiers, whilst Q12 provides a framework to facilitate the management of the entire “Pharmaceutical Product Lifecycle.
1. REGULATORY BODIES IN THE EUROPEAN UNION, JAPAN AND THE USA In the USA, the regulatory function is performed by the Food and Drug Administration (FDA) with technical and scientific support being provided through two centers - the Center for Drug Evaluation and Research (CDER) in respect of medicines and the Center for Devices and Radiologic Health (CDRH) in respect of medical devices e.g. inhalers. A similar function to the FDA is provided by the Ministry of Health, Welfare and Labor (MHWL) in Japan and the European Medicines Agency (EMA) , with support in the form of the Committee for Medicinal Products for Human Use (CHMP) , representing the various states making up the European Union (EU). Other prominent bodies include the Central Drugs Standard Control Organisation (CDSCO) of India, the China Food and Drug Administration (CFDA) , Health Canada and Swissmedic .
2. INTERNATIONAL REGULATION AND HARMONISATION The International Centre for Harmonisation (ICH) mentioned on Page 8 is a unique organisation consisting of representatives from the regulatory authorities in the European Union (EMA), Japan (MHLW) and the USA (FDA), and experts from the pharmaceutical industry in the three regions, in a single forum. The purpose of the ICH is to promote greater harmonisation in the ways in which the individual regulatory bodies regulate new drugs such that the medicine reaches the patient economically and with the minimum delay whilst maintaining the standards of safety, quality and efficacy necessary to safeguard public health. Current goals include finalisation of ICH Q13 (Continuous Manufacturing of Drugs) and ICH Q14 (Analytical Procedure Development.
Note : A similar organisation, the Global Harmonisation Task Force (GHTF) , exists for medical devices.
9
Pharmaceutical Testing
Organisations and their Roles
3. DRUG SAFETY, QUALITY AND EFFICACY – THE PHARMACOPOEIAS The main role of the Pharmacopoeias is to define the standards with which medicines must comply and the methods by which compliance will be adjudged. As with the regulatory groups, the leading Pharmacopoeias tend to be those of the European Union, Japan and the USA. a) European Pharmacopoeia This is published by the Directorate for the Quality of Medicines and Healthcare of the Council of Europe (EDQM). In the European Pharmacopoeia (Ph.Eur. ), the main information relating to a drug product is contained in the general monograph relating to the dosage form concerned (see “Monographs on Dosage Forms”). This normally gives a definition of the dosage form e.g. tablets,
together with notes as to its production and, where
A separate chapter, Pharmaceutical Dosage Forms <1151>, gives a general description and definition of the more common dosage forms together with the general principles
applicable, the test procedures, storage conditions and labelling requirements relevant to that type of product, with cross references to appropriate methods of testing e.g. Uniformity of Dosage Units (2.9.40). The EDQM is also responsible for“ Pharmeuropa ”, a quarterly publication which contains “Draft Monographs and General Texts for Comment” together with the latest news on “International Harmonisation”. b) United States Pharmacopeia Hitherto, the United States Pharmacopeia (USP) has adopted a similar approach to Ph.Eur. with details of the test procedures to be employed together with all of the other relevant information in product specific monographs with cross references to the appropriate methods of testing e.g. Uniformity of Dosage Units <905>.
in their compounding and manufacturing. However, in USP 38 the
Pharmacopeia has introduced a series of new chapters, <1> through to <5>, entitled General Requirements for Tests and Assays , which provide general information and the critical quality attributes applicable to the various dosage forms based on their route of administration (see Table on Page 11). The five chapters concerned detail the test procedures relevant to each dosage form, divided between those relating to product quality and those to product performance , with cross references to the methods of testing as appropriate.
10
Organisations and their Roles
Product quality tests assess physical, chemical and microbial attributes. Product performance tests assess drug release from the dosage form concerned or, in the case of aerosols, particle size distribution.
Like Ph.Eur., USP also produces a bi-monthly publication entitled “Pharmacopeial Forum”, which contains discussion documents relating to new and/or amended chapters and monographs.
NEW USP 38 CHAPTERS <1> to <5>
Product Tests for Quality
Product Tests for Performance
Route of Administration
Site of Release
Typical Dose Forms
Injections, particles, liposomes, implants, stents
<1001> Under development
Injections & Implanted Drug Products (Parentals) Chapter <1>
Body tissues and fluids
<1>
<701> <711>
Tablets and Capsules, Liquids
Oral Drug Products Chapter <2>
<2>
Oral
Semisolids, Transdermal Patches
<724> <1724>
Topical and Transdermal Drug Products Chapter <3>
Skin
<3>
Ear, eye, nose, throat, urether, vagina, rectum
Mucosal Drug Products Chapter <4>
Various see <4>
<4>
<1004>
<601>, <602> <603>, <604>, <1601>, <1602>
Aerosols, sprays, powders
Inhalation and Nasal Drug Products Chapter <5>
<5>
Lung, nasal cavity
11
Pharmaceutical Testing
Disintegration
Background: Disintegration Testing Before the active ingredient(s) of an oral solid dose drug product can be absorbed into the body, the tablet or capsule in which they are contained must first disintegrate into smaller particles. Chapters Ph. Eur. 2.9.1 and USP <701> and <2040> describe reproducible and standardised methods for quantifying the disintegration behaviour of solid dosage forms.
12
Disintegration
Disintegration
Test Apparatus & Method
Typically, the tablets and capsules to be tested are each placed in one of six vertical tubes each measuring approx. 77.5 mm long x 21 mm inside diameter, positioned in a circular basket arrangement.
The lower end of each tube is covered by a 2 mm sieve mesh. Large tablets, capsules and boluses may require a larger basket. The basket assembly is raised and lowered in simulated gastric fluid at body temperature (37 °C) through a distance of 55 mm, at a constant stroke frequency of 30 cycles per minute. A plastic disc of
precise geometry “hammers” the tablet during the operation, thus assisting in the disintegration process. The tablet is said to pass the test providing that no tablet residue remains on the sieve mesh after the designated time, typically 30 minutes for ordinary tablets and 60 minutes for enteric- coated tablets.
A
1.9 ± 0.9
± 1.15 21.85
B
90 ± 2
C
2.6 ± 0.1
A
Basket rack assembly
Basket rack assembly (top view)
B
C
Disc (top view)
9.4 ± 0.2
13
Pharmaceutical Testing
Disintegration: DTGi Series
Reproducible, standardised and affordable disintegration testing
Controlled via our intuitive touchscreen interface, the Copley DTGi Series features 1, 2, 3 and 4 station units as well as a 2-station independent control unit, ideal for testing tablets and capsules under varying conditions. The user-friendly design makes assessing disintegration characteristics a simple touch-of-a-button task. The result of decades of innovation and experience in the field of pharmaceutical testing, the Copley DTGi series of disintegration testers simplifies testing within R&D and QC environments. Suitable for a wide range of tablet and capsule types (e.g. plain-coated tablets, delayed-release, gelatine etc.), the DTGi tester series is an affordable range of disintegration testers, that complies fully with specifications defined in Ph. Eur., USP and associated Pharmacopoeias.
Ph. Eur. and USP compliant
Integrated, precision temperature control and measurement
Intuitive touchscreen control to simplify operation
Single-point electronic temperature calibration
One to four test station unit configurations, plus independent station control unit option
Extensive data reporting output options
Option to automate and remotely control DTGi systems
Adjustable stroke frequency control for accelerated or high sensitivity testing
14
Disintegration
DTGi Series: Key Features
Quick-release baskets for rapid sample loading, unloading and cleaning
Intuitive touchscreen control with icon-based menu structure simplifies operation and clearly displays test parameters throughout run
Robust metal case with advanced corrosion protective coating
Basket rack assemblies are automatically lowered and raised to/from test media at start and end of test
Independent digital heater/ circulator maintains a constant temperature and minimises vibration
Easily removable leak-proof water bath with convenient drain tap eases bath water emptying
PT100 temperature probe monitors bath and media temperature
Maximum fill line indicator
Note: A low-working noise level is generated by the equipment ensuring a comfortable working environment
15
Pharmaceutical Testing
DTGi Series: Touchscreen User Interface
A
B
C
D
E
F
G
Key Features:
• Intuitive menu structure enables users to locate features quickly and easily • Easy-set user-configurable test parameters : Speed (cycles per minute) Temperature (°C) Report output settings menu • Status of ‘Actual’ v ‘Set’ test parameters clearly displayed throughout testing • Test progress bar provides clear and constant indication on run status
• Resistive touchscreen interface can be operated with gloves on • Hygienic wipe-clean screen • Passcode-protected temperature calibration • High productivity - easy system set-up and operation minimises training burden.
16
Disintegration
Reporting
Extensive data output options are available as standard, including direct reporting to a printer or PC.
Reported parameters
• Speed (cycles per minute) Set Average
Setting a test parameter
A
RS 232
Maximum Minimum
Set v Actual test parameters (before test run)
B
• Temperature (°C) Set Average
USB A
Set v Actual test parameters (during test run, with test progress bar)
C
Maximum Minimum
USB B
• Test Duration (HH:MM:SS) Set Actual • Calibration Data Calibration date Temperature calibrated at (°C)
Settings menu
D
Passcode-protected temperature calibration process
E
F
Temperature calibration
Compliance & Maintenance
G
Report output settings menu
Certificate of compliance to Ph. Eur./USP provided as standard Comprehensive IQ/OQ/PQ documentation packages and toolkits available Passcode-protected single-point electronic temperature calibration Latest temperature calibration information stored and available to export/print
✓
✓
✓
✓
17
Pharmaceutical Testing
Choose your DTGi Disintegration System
DTG 100i
DTG 200i
DTG 300i
Cat. Number
Cat. Number
Cat. Number
1231
1232
1233
No. Test Stations
No. Test Stations
No. Test Stations
1
2
3
Tablet Capacity
Tablet Capacity
Tablet Capacity
6
12
18
Independent Station Control
Independent Station Control
Independent Station Control
No
No
No
Unit Dimensions (w x d x h)
Unit Dimensions (w x d x h)
Unit Dimensions (w x d x h)
450 x 473 x 657 mm
450 x 473 x 657 mm
700 x 473 x 657 mm
18
Disintegration
Independent Station Control: DTG 200i-IS
With the same standard features as the other DTGi systems, the DTG 200i-IS offers independent control over each test station, making it ideal for the following types of applications: • Comparing one formulation directly against another • Comparing the performance of a single formulation under different conditions • Assessing delayed release or enteric coated tablets where samples must be immersed for specified periods of time in different media • Allowing two users to run tests simultaneously
DTG 400i
DTG 200i-IS
Cat. Number
Cat. Number
1234
1238
No. Test Stations
No. Test Stations
4
2
Tablet Capacity
Tablet Capacity
24
12
Independent Station Control
Independent Station Control
No
Yes
Unit Dimensions (w x d x h)
Unit Dimensions (w x d x h)
700 x 473 x 657 mm
515 x 473 x 657 mm
19
Pharmaceutical Testing
DTGi Series: Technical Specifications Pharmacopoeial Compliance
Ph. Eur. Chapter: 2.9.1 USP Chapter: <701> and <2040>
User Interface
Resistive touchscreen
Basket Rack Assembly
Automatically lowered and raised at beginning and end of test run
Stroke Frequency Range
10 - 50 strokes/min
Stroke Height
55 ± 1 mm
Heater Type
Independent digital heater/circulator
Heater Temperature Range
Ambient - 50 °C
Test Run Time
Up to 99 hours , 59 minutes, 59 seconds
Alarm(s)
1. End of testing (audible)
2. Low bath water level warning on-screen indicator
Data Output
RS 232 USB A (for connection with a USB printer) USB B (for connection with a PC)
Temperature Calibration
Single-point electronic temperature calibration . Calibration of the DTGi Series temperature probe is simple, through the use of an electronic calibration key and passcode-protected calibration menu
designed to guide users through the process without fuss. The latest temperature probe calibration information is stored and available to print/export when convenient to the user.
Electronic Temperature Calibration Key
DTGi Series
Cat. No. Description
1231 1232 1233 1234 1238 1205 1206 1209 1228 1229 1307
Disintegration Tester Model DTG 100i Disintegration Tester Model DTG 200i Disintegration Tester Model DTG 300i Disintegration Tester Model DTG 400i Disintegration Tester Model DTG 200i-IS
Extra for Numbering and Certification (per basket)
IQ/OQ/PQ Documentation Pack
Electronic Temperature Calibration Key
Qualification Tools
Re-Calibration of Qualification Tools
Printer (including USB cable)
20
Disintegration
Choose your DTGi System Accessories Copley offers a complete range of accessories for use with the DTGi Series, from complete basket-rack assemblies to individual tubes, discs and sieve meshes. All parts are manufactured to tolerances that are equal to or better than those quoted in the respective Pharmacopoeias. Certificates of Compliance can be supplied upon request.
DTGi Series Accessories
Cat. No. Description
1210 1205 1211 1212 1213 1214
Standard Basket Rack Assembly
Extra for Numbering and Certification (per basket)
Set of 6 Glass Tubes for Standard Basket
Set of 6 Polycarbonate Discs for Standard Basket Set of 6 Sieve Meshes for Standard Basket
1000 mL Beaker
Accessories for Specialist Dosage Forms
Cat. No. Description
1215 1216 1217 1218 1219 1220 1221
Basket Rack Cover for Hard & Soft Gelatine Capsules Extra for Numbering and Certification (per cover) Special Basket Rack Assembly for Large Tablets & Capsules Extra for Numbering and Certification (per basket)
Set of 3 Tubes for Special Basket
Set of 3 Cylindrical Discs for Special Basket
Sieve Mesh for Special Basket
Hygiene: Anti-Bacterial/Algae Treatment
The addition of 1 mL of Aqua Stabil per month will prevent the build-up of bacteria and algae in the water bath, keeping the water clear, safe and odour-free.
Cat. No. Description
1372
100 mL Bottle of Aqua Stabil
21
Pharmaceutical Testing
Dissolution
Background: Dissolution Testing Optimising the amount of a drug available to the body following administration, i.e. its bioavailability, remains one of the greatest challenges the pharmaceutical industry faces. Inadequacies in bioavailability can mean a treatment is ineffective or even potentially dangerous (e.g. overdose).
22
Dissolution
The effectiveness of tablets or capsules administered orally relies on the drug dissolving in the fluids of the gastrointestinal tract prior to absorption into the systemic circulation. It is widely acknowledged that the rate at which the drug dissolves is critical to its therapeutic efficacy and as such, is considered a Critical Quality Attribute (CQA) in both the formulation process and final quality control. Determining bioavailability via in vivo drug release analysis studies (e.g. urine or plasma analysis) can be impractical, particularly when such techniques are required on a routine basis. To overcome such issues, official in vitro dissolution tests have been rigorously and comprehensively defined in the respective Pharmacopoeias and are essential for: • Predicting in vivo drug bioavailability • Assessing bioequivalence and its application in scale-up and post-approval changes • Optimising therapeutic effectiveness during development and stability assessment • Ensuring uniformity between production lots
A
B
Dissolution Vessel
9.4 to 10.1
Stiring Element
B
A
42.11
Stiring Element
Vessel with stiring element designed to simulate conditions within the gastrointestinal tract
A
B
Dissolution methods aim to provide important in vitro drug release information for both drug development and quality control purposes.
Initially developed for oral dosage forms, the role of the ‘dissolution test’ has now been expanded to the ‘drug release’ of various other forms such as semisolids topical and transdermal systems (see page 74).
23
Pharmaceutical Testing
Dissolution
Test Apparatus & Method
The progressive optimisation of dissolution testing for different pharmaceutical forms has led to the introduction of a range of different apparatuses and techniques as detailed in Ph. Eur Chapters 2.9.3, 2.9.4 and USP Chapters <711> and <724>.
With the paddle method, the basket is replaced by a paddle and the sample to be tested is allowed to sink to the bottom of the vessel. During a test run, a motor is used to rotate the shaft at a speed specified by the appropriate Pharmacopoeias. The paddle over disk technique is used for the determination of the drug release rate from transdermal patches. It is described in the Ph. Eur. under Chapter 2.9.4 and under Chapter <724> as Method 5 in the USP. Using a suitable adhesive, the transdermal patch is simply mounted on a disk designed to hold it at the bottom of the vessel. The rotating cylinder (Ph. Eur. Chapter 2.9.4, USP Method 6) is an alternative to the paddle over disk method.
The most commonly used apparatus defined by the Pharmacopoeias to measure the dissolution rate of solid dose forms are the basket and paddle . The basic dissolution apparatus consists of a covered cylindrical vessel with a hemispherical bottom, typically holding 1000 mL of simulated gastric juice. The vessel is immersed in a water bath capable of maintaining the temperature of the vessel contents at 37°C. For the basket method, the tablet or capsule is constrained in a cylindrical basket, constructed of sieve mesh, of defined proportions. The basket is attached to a metal drive shaft, positioned so that the bottom of the basket is 25 mm from the bottom of the vessel.
Basket Paddle Ph. Eur. 2.9.3
Flow-Through Cell Ph. Eur. 2.9.3
Paddle Over Disk Ph. Eur. 2.9.4
Basket Ph. Eur. 2.9.3
Reciprocating Cylinder Ph. Eur. 2.9.3
USP App 3 <711>
USP App 1 <711>
USP App 2 <711>
USP App 4 <711>
USP App 5 <724>
24
Dissolution
Samples of the dissolution medium are taken at predefined time intervals to determine the percentage of dissolved drug present – typically using a UV/Vis Spectrophotometer or high-pressure liquid chromatography (HPLC). Dissolution of all but the most specialised oral pharmaceutical dosage forms can be tested with either the basket or paddle methods. Other techniques specified in the USP for dissolution testing include: Reciprocating Cylinder (Apparatus 3), Flow-Through Cell (Apparatus 4) and Reciprocating Holder (Apparatus 7). These are not routinely required except for highly specialised dosage forms.
Cylinder Ph. Eur. 2.9.4
Reciprocating Holder -
Vertical Diffusion Cell -
Special Immersion Cell -
- Special Suppository Basket -
USP App 6 <724>
USP App 7 <724>
USP <1724>
USP <1724>
25
Pharmaceutical Testing
Dissolution: DISi Series
Expertly engineered systems for everyday dissolution testing
Ideal for use in both R&D and QC environments, the DISi Series is equipped with precision ground shafts that will accept any of the baskets, paddles or rotating cylinders described in the Ph. Eur., USP and associated Pharmacopoeias. Designed to minimise user training and reduce the burden of routine equipment maintenance, the DISi Series simplifies the dissolution testing process, without compromising on data quality. Meeting the latest specifications as laid down in the European, United States and associated Pharmacopoeias, the DISi Series from Copley is a range of reliable and cost-efficient dissolution tester systems designed with the highest standards of solid dosage testing performance in mind.
Integrated, precision temperature control and measurement
Ph. Eur. and USP compliant
Intuitive touchscreen control to simplify operation
Single-point electronic temperature calibration
Extensive data output options
Six and eight test station unit configurations available
Wide speed range to accommodate broad scope of methods
Option to automate and remotely control DISi Systems
26
Dissolution
DISi Series: Key Features
Easy-clean Viton® membrane-sealed zero-evaporation lids included as standard
Intuitive touchscreen control with icon-based menu structure simplifies operation
Robust metal case with advanced corrosion protective coating
PT100 temperature probe monitors bath and vessel temperature with electronic calibration feature
Independent digital heater/circulator maintains a constant temperature and minimises vibration
Note: Full automation-compatible to support high-throughput workflows
Easily removable leak-proof water bath with convenient drain tap eases bath water emptying
All vessels are serial-numbered as standard
Maximum fill line indicator
Convenient screw-in basket/paddles enable easy method change in seconds
‘Easy-Centre’ centring system for precise vessel positioning
27
Pharmaceutical Testing
DISi Series: Touchscreen User Interface
A
C
B
D
E
F
G
H
Key Features:
• Intuitive menu structure enables users to locate features quickly and easily • Easy-set user-configurable test parameters : Speed (revolutions per minute) Temperature (°C) Test duration (HH:MM:SS) • Status of ‘Actual’ v ‘Set’ test parameters clearly displayed throughout testing • Test progress bar provides clear and constant indication of run status
• Resistive touchscreen interface can be operated with gloves on • Hygienic wipe-clean screen • Passcode-protected temperature calibration • High productivity - easy system set-up and operation minimises training burden
28
Dissolution
Reporting
Extensive data output options are available as standard, including direct reporting to a printer or PC.
Reported parameters
• Speed (revolutions per minute) Set Average
A
Setting a test parameter
RS 232
Maximum Minimum
Set v Actual test parameters (before test run)
B
• Temperature (°C) Set Average
USB A
Set v Actual test parameters (during test run, with test progress bar)
C
Maximum Minimum
USB B
D
Settings menu
• Test Duration (HH:MM:SS) Set Actual • Calibration Data Calibration date Temperature calibrated at (°C)
Passcode-protected temperature calibration process
E
Temperature calibration
F
Compliance & Maintenance
Report output settings menu
G
H
Motor speed (RPM) verification
Certificate of compliance to Ph. Eur./USP provided as standard Comprehensive IQ/OQ/PQ documentation packages and toolkits available Passcode-protected single-point electronic temperature calibration Latest temperature calibration information stored and available to export/print
✓
✓
✓
✓
29
Pharmaceutical Testing
Choose your DISi Dissolution System
DIS 600i
DIS 800i
Maximising visibility and access to the critical sampling area above the bath, the DIS 800i represents the very latest in tablet dissolution testing technology.
With bench space a premium in many laboratories, the DIS 600i is one of the most compact dissolution testers available on the market today.
Cat. Number
Cat. Number
1336
1338
No. Stirred Vessels
No. Stirred Vessels
6
8
Ph. Eur. and USP Test Methods Supported
Ph. Eur. and USP Test Methods Supported
1, 2, 5, 6
1, 2, 5, 6
Heater
Heater
Low vibration integrated digital heater/circulator
Low vibration independent external digital heater/circulator
Unit Dimensions (w x d x h)
Unit Dimensions (w x d x h) 728 x 495 x 689 mm (unit) 260 x 330 x 150 mm (heater)
728 x 495 x 689 mm
30
Dissolution
DISi Series: Technical Specifications Pharmacopoeial Compliance
Ph. Eur. Chapters: 2.9.3, 2.9.4 USP Chapters: <711> <724>
User Interface
Resistive touchscreen
Speed Range
20 - 220 rpm +/- 2%
Heater Accuracy
± 0.1°C
Heater Temperature Range
Ambient - 50°C
Vibration Elimination
Low vibration heaters
Test Run Time
Up to 99 hours, 59 minutes, 59 seconds
Alarm(s)
1 . End of testing (audible)
2 . Low bath water level warning on-screen indicator
Data Output
RS 232 USB A (for connection with a USB printer) USB B (for connection with a PC)
Temperature Calibration
Single-point electronic temperature calibration . Calibration of the DISi Series temperature probe is simple, through the use of an electronic calibration key and passcode-protected calibration menu
designed to guide users through the process without fuss. The latest temperature probe calibration information is stored and available to print/export when convenient to the user.
Electronic Temperature Calibration Key
DISi Series
Cat. No.
Description
1336 1338 1209 1309 1307
Dissolution Tester DIS 600i (incl. 6 Drive Shafts) Dissolution Tester DIS 800i (incl. 8 Drive Shafts)
Electronic Temperature Calibration Key
IQ/OQ/PQ Documentation Pack Printer (including USB cable)
31
Pharmaceutical Testing
Choose your DISi System Accessories All DISi Series are equipped with precision-ground shafts that will accept any of the baskets, paddles or rotating cylinders described in the Pharmacopoeias. Each clutch can be raised, lowered or engaged independently of the drive head, ensuring users have maximum accessibility to the vessels, whilst also making the systems suitable for staggered starts. Each element can be supplied with a Teflon coating for additional protection against aggressive media, if required and can be laser numbered and certified upon request.
Baskets, Paddles & Rotating Cylinders
Basket Stirring Elements (Ph. Eur. /USP Method 1)
Cat. No.
Description
1302B 1302A
Set of 6 Baskets (Ph.Eur./USP Method 1) Set of 8 Baskets (Ph.Eur./USP Method 1) Basket only in 316 Stainless Steel (40 mesh)
1302 1317 1331 1333
Basket Holder in 316 Stainless Steel
3-Prong Retention Spring in Hardened 17-7 Steel Basket Stirring Element complete with Drive Shaft
Paddle Stirring Elements (Ph. Eur. /USP Method 2)
Cat. No.
Description
1304B 1304A
Set of 6 Paddles (Ph.Eur./USP Method 2) Set of 8 Paddles (Ph.Eur./USP Method 2)
1304 1341 1343
Paddle only in 316 Stainless Steel
Paddle Stirring Element complete with Drive Shaft Paddle Stirring Element complete – Teflon Coated
Dissolution Drive Shaft
Cat. No.
Description
1329
316 Stainless Steel Drive Shaft only
Capsule Sinkers & Weights
Cat. No.
Description
1356
Set of 6 316 Stainless Steel Sinkers Set of 8 316 Stainless Steel Sinkers Set of 6 USP/Ph.Eur. Alternative Sinkers Set of 8 USP/Ph.Eur. Alternative Sinkers Wire, 316 Stainless Steel (50 ft length)
1356A
1345
1345A
1348 1357
Set of 6 3-Prong Plastic Sinkers
Disintegration 02 32
Dissolution
Vessels Compliant with Ph. Eur. and USP specifications, all DISi Series vessels feature unique Easy-Centre systems ensuring perfect positioning every time. Locking the vessel into the correct position relative to the drive shaft, the fixture ensures that the vessels will not become loose or float, even when empty. UV-resistant vessels are also available for products sensitive to UV. Easy-clean Viton® membrane-sealed low evaporation lids are included as standard with each vessel.
Vessels
Cat. No.
Description
1344 1346 1352 1349 1366
Vessel, 1000 mL
Vessel, 1000 mL, with “Easy-Centre”
Amber Vessel, 1000 mL
Amber Vessel, 1000 mL, with “Easy-Centre”
“Easy-Centre” Vessel Ring
EMC Ultra-Precision Dissolution Vessels
With dimensional tolerances a factor of 2 higher than those specified in the FDA Enhanced Mechanical Calibration, the EMC Ultra-Precision Dissolution Vessel brings even higher levels of accuracy to dissolution testing. All relevant parts are individually serialised as standard.
4
1. Inside Diameter
101.19 +/- 0.13 mm
5
1
2. Inside Spherical Radius
50.59 +/- 0.13 mm Radius
3. Height
154.75 +/- 0.50 mm
6
(Inside Spherical Radius to top)
4. Flange OD
120.00 +/- 0.50 mm
3
5. Flange Thickness
3.50 +/- 0.50 mm
2
6. Perpendicularity
0.50° Max
(Inside Vessel Dia. to Flange Underside)
Cat. No.
Description
1398
EMC Dissolution Vessel, 1000 mL, with “Easy-Centre”
Vessel Covers
Cat. No. Description
1354 1393 1394 1355
Vessel Cover for DIS 600i/800i
Automatic Tablet Drop Vessel Cover (Set of 6 for DIS 600i) Automatic Tablet Drop Vessel Cover (Set of 8 for DIS 800i)
Plug for Vessel Cover
Vessel Cover for DIS 600i/800i
Automatic Tablet Drop Vessel Cover for DIS 600i/800i
Dissolution 03 33
Pharmaceutical Testing
Eliminate the need for time-lag correction factor calculations with the Automatic Tablet Drop system. Guaranteeing simultaneous tablet ejection at the start of the test run, synchronised sampling is simplified. Automatic Tablet Drop
Cat. No. Description Automatic Tablet Drop 1393
Automatic Tablet Drop Vessel Cover (set of 6 for DIS 600i) Automatic Tablet Drop Vessel Cover (Set of 8 for DIS 800i)
1394
Sampling Probes Choose from a range of dissolution sampling probe systems, optimised for different user requirements: 1. Manual sampling cannula : with a Luer fitting to accept a 20 mL syringe, bent at the top to enable easy positioning within the dissolution vessel. 2. Resident probe : designed to be left in-situ in the dissolution vessel for the duration of the test and is height adjustable, in accordance with differing methods described in the pharmacopoeias. 3 different types are available: a . For automated systems: fitted with Omnifit fittings used in conjunction with the return line inserts b . For automated systems: fitted with Omnifit fittings c . For manual sampling (with Luer fittings)
a.
b.
c.
34
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