A

Report
On

Generation and Validation of Standard

Operating Procedure for Dissolution
Apparatus.

By

ABHISHEK JHA
(Roll No. 1509050001)

B. Pharm - 4th Year

2018-19

Submitted to

Department of Pharmacy, IEC Group of Institutions

Knowledge Park-1, Institutional Area, Surajpur Kasna Road,
Greater Noida, Gautam Budh Nagar, Uttar Pradesh-201310, (India)

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 CONTENTS

1. Acknowledgement

2. Certification

3. Introduction

4. Equipment

5. Validation

6. Qualification

7. Dissolution apparatus

8. Conclusion

9. Reference

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 ACKNOWLEDGEMENT

I would like to express my special thanks of gratitude to IEC College of Engineering

And Technology for their able guidance and support in completing my project work.

I respect and thank Ms. [Aparna Datta], for providing me an opportunity to do the
project work on “Generation and Validation of Standard Operating Procedure for
Dissolution Apparatus”. in IEC college of Engineering and Technology,
“Department of pharmacy” and giving us all support and guidance which made me
complete the project duly.

I am extremely thankful to Mr. Manoj Kumar Prabhakar ( HOD “Department of

pharmacy”) for providing such a nice support and guidance, although he had busy
schedule managing the College programs.

I am thankful to and fortunate enough to get constant encouragement, support and

guidance from all Teaching staffs of “Department of pharmacy” which helped us in
successfully completing our project work. Also, I would like to extend our sincere
esteems to all staff in laboratory for their timely support.

ABHISHEK JHA MS. Aparna Datta

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 CERTIFICATION

To whom it may concern certificate

This is to certify that Mr. Ahishek Jha bearing Roll no. “1509050001” is a bonafide
student of UG Bachelor of Pharmacy program the institute IEC College of Engineering
and Technology currently he is a student of 8th semester.

This certificate is issued for the purpose of project work on “Generation and
Validation of Standard Operating Procedure for Dissolution Apparatus”.

(HOD-Department of Pharmacy)

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INTRODUCTION
In the pharmaceutical industry, drug dissolution testing is routinely used to provide
critical in vitro drug release information for both quality control purposes, i.e., to
assess batch-to-batch consistency of solid oral dosage forms such as tablets, and drug
development, i.e., to predict in vivo drug release profiles.

The main objective of developing and evaluating an IVIVC is to establish the

dissolution test as a surrogate for human studies, as stated by the Food and Drug
Administration (FDA).

Analytical data from drug dissolution testing are sufficient in many cases to
establish safety and efficacy of a drug product without in vivo tests, following minor
formulation and manufacturing changes.

Thus, the dissolution testing which is conducted in dissolution apparatus must be able
to provide accurate and reproducible results.

DISSOLUTION AAPRATUS

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EQUIPMENTS

Several dissolution apparatuses exist. In United States Pharmacopeia (USP)

Dissolution, there are four dissolution apparatuses standardized and
specified. They are:

 USP Dissolution Apparatus 1 – Basket (37 °C)

 USP Dissolution Apparatus 2 – Paddle (37°C)
 USP Dissolution Apparatus 3 – Reciprocating Cylinder (37 °C)
 USP Dissolution Apparatus 4 – Flow-Through Cell (37 °C

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GENRAL METHOD
The vessels of the dissolution method are usually either partially immersed
in a water bath solution or heated by a jacket.

An apparatus is used on solution within the vessels for a predetermined

amount of time which depends on the method for the particular drug. The
dissolution medium within the vessels are heated to 37°C with an
acceptable difference of ± 0.5°C

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The performances of dissolution apparatuses are highly dependent on
hydrodynamics due to the nature of dissolution testing.

The designs of the dissolution apparatuses and the ways of operating

dissolution apparatuses have huge impacts on the hydrodynamics, thus the
performances.

Hydrodynamic studies in dissolution apparatuses were carried out by

researchers over the past few years with both experimental methods and
numerical modeling such as Computational Fluid Dynamics (CFD). The
main target was USP Dissolution Apparatus 2.

The reason is that many researchers suspect that USP Dissolution

Apparatus 2 provides inconsistent and sometimes faulty data.

The hydrodynamic studies of USP Dissolution Apparatus 2 mentioned

above clearly showed that it does have intrinsic hydrodynamic issues which
could result in problems.

VALIDATION
Validation is process of establishing documented evidence that provides
high degree of assurance that specific process will consistently produce a
product meeting its predetermined specifications and quality.

REASONS FOR VALIDATION

 To improve Quality of Pharmaceuticals.
 To design system properly to provide high degree of assurance.
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 Equipment validation

Facilities validation

HVAC Validation

VALIDATION
XXX Cleaning Validation

Process validation

Analytical method validation

Computer system validation

DISSOLUTION
Dissolution is defined as the process by which a known amount of drug
substance goes into solution per unit of time under standardized conditions.
The primary goal of dissolution testing is to be used as a qualitative tool to
provide measurements of the bioavailability of a drug as well as to
demonstrate bioequivalence from batch-to-batch.

The bioavailability and bioequivalence data obtained as a result of

dissolution testing can be used to guide the development of a new
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formulation and product development processes toward product
optimization, as well as to ensure continuing product quality and
performance of the manufacturing process.

In addition, dissolution is a requirement for regulatory approval for product

marketing and is a vital component of the overall quality control program.
Dissolution testing is conducted using a dissolution apparatus that conforms
to the specifications outlined in the United States Pharmacopeia.

There are seven types of dissolution apparatus the apparatus chosen to

perform dissolution testing depends primarily on the drug dosage form.
In order to have a high degree of assurance that the dissolution apparatus is
consistent and accurate in its performance, validation is required.

Validation is defined as documented evidence that provides a high degree

of assurance that a specific instrument performs according to
manufacturer’s specifications and user requirements. Validation is achieved
by performing a series of validation activities; for a dissolution apparatus,
validation is obtained through installation qualification and operational
qualification.

NEEDS OF DISSOLUTION TESTING

1. To ensure continuity of product quality & performance of manufacturing

process
2. Requirement for regulatory approval for product marketing

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QUALIFICATION

To ensure that equipment is fit for intended purpose, there are no. of qualifying steps
that vendor / analyst should apply to analytical instruments.
Equipment is evaluated through these tests & successful completion justifies
instrument operates and performs as expected.

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DESIGN QUALIFICATION

When developing dissolution method DQ is built into apparatus selection of process,

Dosage form & delivery system will determine choice of equipment.
Example-first choice for beaded product may be USP app 3…… as it is designed to
confine beads in a screened-in cylinder.

INSTALLATION QUALIFICATION
Installation qualification consists of documented verification that all key aspects of
the dissolution apparatus are in working condition and have been properly installed in
accordance with manufacturer’s specifications in the proper operating environment.
The installation qualification of a dissolution apparatus should include the following
verifications:
• Preventive maintenance
The installation qualification should document that the dissolution apparatus is
enrolled in a preventive maintenance program to assure that the system continues to
operate properly and no component part of the sys-tem becomes inoperable due to
wear and use.
• Calibration
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 The installation qualification should document that specific devices contained
within the dissolution apparatus (e.g., speed, time, and temperature displays) have
been calibrated to traceable standards. Documentation should include the date
calibration was performed and when calibration is due.
• SOPs
The installation qualification should document that all SOPs pertaining to the
dissolution apparatus are approved and in place. Applicable SOPs may
include preventive maintenance, calibration, operation, document archival,
and equipment logbook usage.
• Utilities
The installation qualification should document the manufacturer’s
specifications for required utilities and verify that the appropriate utilities are
available for the system. For example, utility verification may include
confirming that the appropriate electrical power requirements (voltage,
amperage, safety cut-offs) are documented and comply with manufacturer’s
specifications.
• Computerized System
If the dissolution apparatus is computerized, the installation qualification
should document the manufacturer’s specifications for the computer system
and verify that the computer system in place complies with manufacturer’s
specifications. Documentation should include model and serial number of
associated hard-ware, operating system name and version, software name and
version, location of master and back-up files, and CPU requirements such as
speed and hard drive capacity.

OPERATIONAL QUALIFICATION
Operational Qualification consists of documented evidence that the equipment
operates as intended and is capable of consistent operation within established
specifications. The operational qualification of a dissolution apparatus should include
the following verifications:
• System Suitability (Calibration)
A system suitability test using USP calibrators should be conducted during
operational qualification testing. The procedure for dissolution and sampling is
outlined in the Certificates supplied with each USP Calibrator tablet for each
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 apparatus. The calibrators used for the test are disintegrating tablets (Prednisone)
and non-disintegrating tablets (Salicylic Acid).
The test is considered successful if the percent of drug released at 30 minutes falls
within a pre-established range.
The ranges for each combination of apparatus and calibrators at 50 or 100 RPM are
established by the USP and are different for each lot of calibrators. This test must be
conducted for each of the vessels contained within a dissolution apparatus. For a
vessel to be acceptable, it must, individually, provide acceptable drug release from
the calibrator.
• Temperature Distribution Study
A temperature distribution study should be conducted during the
operational qualification. The study should include temperature
mapping of each vessel contained within the dissolution apparatus.
Temperature should be mapped using a data acquisition system for a
minimum time that is based on the monograph or 1 hour, whichever is
greater. The temperature of Apparatus 1, 2, 3, and 4 must remain at
37°C ± 0.5°C; the temperature of Apparatus 5 and 6 must remain at
32°C ± 0.5°C.
• Rotation Speed Study
A rotation speed study should be conducted during the operational
qualification. The study should include a measurement of the speed of the
shaft rotation for each vessel contained within the dissolution appara-tus.
Speed should be measured using a photo tachometer for 30 minutes or the time
specified in the individual monograph, whichever is greater. The speed of the
shaft rotation should be verified to be within 4% of the speed specified in the
monograph.

PERFORMANCE QUALIFICATION
This is conducted to ensure that system is in normal operating environment
& performing designed set of tasks within the specifications.
Example:-Centering, wobble, height of paddle or basket attached to shaft,
speed, temperature.

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DISSOLUTION TEST APPARATUS
1. NON COMPENDIAL
2. COMPENDIAL

 NON –COMPENDIALEQUIPME
Rotating bottle, mini paddle, mega paddle, beaker method, peak
vessel, diffusion cells, chewing gum apparatus etc.

 . COMPENDIAL EQUIPMENTS
USP APPRATUS

SOURCES OF ERRORS
1. Drug substance properties
2. Drug product properties
3. Equipment
4. Method consideration
5. Observation
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6. Automation
7. Cleaning
8. Method transfer

SOURCES OF ERRORS
A] Drug substance properties e.g. Solubility, pH
B] Drug product properties Mechanical, formulation
C] Equipment Mechanical & chemical aspects, Apparatus suitability test
D] Method consideration To avoid errors Film coated tablets-sticky-sinker
Suspension-syringe/pipette/beaker Medium-volume difference Presence of
surfactants.
E] Observation Sinkers-turns of wire helix-its effect Manual sampling
F] Automation Problems-disconnection, inadequate cleaning, mix-ups
G] Cleaning Many products, same equipment major source of error.
H] Method transfer Sinkers, dispensing apparatus, sampling methods,
precise medium, standard preparations, grade of reagents.

Conclusion

At the conclusion of acceptable installation and operational

qualifications, the dissolution apparatus is considered validated and
acceptable for use to perform dissolution testing.

The system suitability tests should be per-formed after any significant

equipment change (e.g., a change from a basket apparatus to a paddle
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apparatus, unless multiple apparatus are qualified at the time of
validation) or relocation of the dissolution apparatus (e.g., to another
laboratory).

Barring any significant change, the system suitability tests should be

conducted at least twice a year as part of a robust preventive
maintenance program.

References

1. Ansel, Howard C., Lloyd V. Allen, Jr., and Nicholas G.

Popovich. Pharmaceutical Dosage Forms and Drug Delivery
Systems. Baltimore, Maryland: Lippincott Williams & Wilkins,
7th edition, 1999.
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2. United States Pharmacopeial Convention, Inc. United States
Pharmacopeia 26. Rockville, Maryland: United States
Pharmacopeial Convention, Inc. 2003.
3. Qureshi, S.A. “The USP Dissolution Apparatus Suitability Test.”
Drug Information Journal. 1996; 30; 1055-1061.

4. GAMP Guide Forum. GAMP 4. GAMP Guide Forum and ISPE.

2003.

5. Food and Drug Administration. Guidance for Industry, Dissolution

Testing of Immediate Release Solid Oral Dosage Forms.
Rockville, Maryland: Food and Drug Administration, Center for
Drug Evaluation and Research. 1997.

6. https://en.wikipedia.org/wiki/Dissolution_testing

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