Excipient Quality &Trouble Shooting
By
Seema Trivedi
GM, TechnicalBack Ground• The Society for Pharmaceutical Dissolution Science (SPDS) had held its 6th
Annual International Convention Disso India - Hyderabad 2018 on June 28and 29, 2018 at Hotel Avasa, Hyderabad. The event promoted introductionof new technology, innovation and had deliberations on various issues
faced related to Dissolution.
• Disso India - Hyderabad 2018 had eminent professionals from thepharmaceutical industry. Few of them are• Dr. Anant Ketkar, Sun Pharma Advanced Research Company; Dr. Chuei
Wuei Leong, founder and principal consultant, CEXA Consultancy Sdn Bhd,Malaysia; Dr. Namita Tipnis, University of Connecticut, USA;
• Dr. Sandip Tiwari, fellow, manufacturing science and technology, Actavis
Laboratories FL, Inc., Florida, USA; Seema Trivedi, GM Technical, Anshul
Life Sciences, India; Prof. Umesh Banakar, professor and president,
BanakarConsulting
Services,USA;etc.

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2Content•••
••••
•••

Definition of Excipient
Excipient Needs
Understanding Excipient
Central Role of Dissolution
Factors affecting in-vitro dissolution
Role of Excipient in Dissolution
Critical Quality Attributes
Case Studies of Analysis
Conclusion
Anshul Portfolio
ANSHUL LIFE SCIENCES 20183Definition of Excipient
Any substance, other than the active drug that has been
appropriately evaluated for safety and is included in a drugdelivery system to either aid the processing of drug delivery
system during its manufacture, protect, support or enhancestability, bioavailability or patient acceptability, or assist inproduct identification or enhance any other attribute of theoverall safety and effectiveness of the drug delivery system
during storage or use.

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Excipient Needs
Exhibit no lotto-lot
variability inproperties &functionality
Cost Effective

Available
worldwide,
meeting
globalrequirements

Physiologically
Inactive

Easy to store
Wellcharacterized& madeunder GMPs –Compatible
with otherexcipients

Availablefrom multiple
vendors

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Understanding Excipients

Excipient
EnablesAPI

Major
source ofvariability

QbD

Impacts
CQA

Source ofImpurity

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Patient
SafetySpeed toMarket6

Central role of Dissolution

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Role of Excipients in Dissolution“Disintegrant”

dissolution

Schematic representation of tablet disintegration and subsequent drug dissolution
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Types of Disintegrants
Disintegrants

Mechanism

Effective
Concentration

Starch and Modified Starch

Swelling

5-10%

Microcrystalline cellulose

Swelling

10-20%

Croscarmellose Sodium

Wicking and swelling

1.0-4.0%

Sodium Starch Glycollate

Rapid and extensive swelling

4-6 %Crospovidone

Wicking, swelling anddeformation

2.0-4.0 %Sodium Bicarbonate incombination acid

Effervescent Disintegrant
Gas formation-Super disintegrants are effective in lower concentrations and offer
significant improvements over disintegrants like starch and MCC
eg: Sodium Starch Glycolate, Croscarmellose Sodium, Crospovidone

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Effect of Super-disintegrantTime in minutes

T80 of water-soluble cationic drugs

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Effect of Super-disintegrantTime in minutes

T80 of poorly soluble cationic drugs.

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Role of Excipient in Dissolution
Diluents
FORMULA FOR GRISEOFULVIN TABLETS

Release profiles of griseofulvin from the formulated andcommercial Samples
lactose (─♦─), sucrose (─■─), mannitol (─▲─) anddextrose (─×─) Fulcin® (─ж─), a commercially available
sample.
Effect of Hydrophilic Diluents on the Release Profile of Griseofulvin from Tablet Formulations
O. N. C. Umeh,* J. C. Azegba, and S. I. Ofoefule

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Fulcin: MCC, SLS,Povidone, starch (cornand Potato), Mag stearate

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Role of Excipient in Dissolution
Polymers in Modified Release

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Role of Excipient in Dissolution
Effect of Ethyl Cellulose Viscosity
Venlafexine HCl (VFH) dissolution
Medium : 900 ml of 0.1N HCl; Apparatus: Paddle, Speed 50 rpm(10% weight gain)

Note: Ethyl Cellulose from Asha Cellulose was used in this study

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Critical Quality Attributes
Functionality Tests are critical Quality attributes for Performance

Diluent

Disintegrants-PSD-Bulk Density-LOD

Binders-Viscosity-PSD-Swell volume-LOD-MolecularweightExcipients
LubricantCoating-PSD
ReleaseModifier-Substitution-Viscosity-Substitution-Viscosity
ANSHUL LIFE SCIENCES 201816Case Studies

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Case Study- I
Microcrystalline Cellulose- Diluent
Problem: Percentage particles passing through 200 mesh was out ofspecification (OOS) on the higher limit• Investigationo Samples were drawn from different boxes by using sampling thief fromvarious points (top, middle and bottom) and mixedo Sieve Analysis was carried out using calibrated sieveo Vibratory sieve shaker was used
• Probable causeo Batch representationo Sieves were not calibrated• Corrective actiono Calibrated Sieve to be usedo Batch representative Sampling

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Case Study II
Hydroxy Propyl Methyl Cellulose- Polymer
Problem : Out of specification results for Viscosity of Hypromellose 100,000 cps• Root Cause– Solution Preparation
Non-uniform solution preparation due to▪ Non uniform dispersion in hot water▪ Immediate cooling▪ Heat transfer in high viscosity solution is very slow and the lower,
Middle and upper part in solution can be different▪ The swelled part is not visible, which can contribute to higher viscosity• Corrective action:– Solution Preparation (on next slide)▪ The dispersed powder should be treated at 20~40 min in ice water▪ After the solution attains 20º C in ice water, transfer it to 20º C bath
▪ The viscosity is measured at different positions
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Solution Preparation Viscosity

1.Heat water
above 90 º C

2. Add HPMC
above 90 º C
under stirring

3. Agitate till
wetting anduniform
dispersion isobtained

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4. Cool to20ºC
transparentsolution

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Case Study III
Super-DisintegrantProblem: Moisture Content : Out of specification results were obtained forMoisture Content• Root cause:– Crospovidone is a highly hygroscopic material– Due to hygroscopicity, the sample had picked up moisture due to• Improper packing of sample• Time gap between sampling and analysis• Corrective Action:– Notification on precautions to be taken during handling ofCrospovidone for sampling, analysis and manufacturing accompanies
the material– The label states that the material is hygroscopic in nature

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Conclusion
Excipients are inert but play a vital role in formulating astable product with efficacy and safetyDifferent grades are available to cater to the specificneeds of API

Selection of excipient is critical to have a bioequivalent/bioavailable drug productCritical quality attributes are functional tests which
differentiate between excipient quality

Analytical Errors in CQA can lead to failure and rejectionof the material
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Anshul Life Sciences
An Introduction• Established in 1978.
• Over the years, Anshul from an indenting agency has now become apartner in innovation and value addition to many customers• Has a strong customer base of over 800• Has a good track record of being an ethical and reliable company in
the Specialty Chemicals, Excipients & Ingredients space.

• Has an application lab of Pharma, Personal care and Food to caterto the needs of customers

Anshul Product Portfolio❖ Microcrystalline Cellulose❖ Croscarmellose Sodium❖ Sodium CMC + MCC ❖ Hypromellose❖ Hypromellose Phthalates❖ Lactoses❖ Saccharins❖ Cyclamates❖ Povidones❖ Crospovidones❖ Copovidone❖ Polysorbate 80❖ PEG❖ Directly Compressible Gum Basesfor medicated Chewing Gums ❖ Poloxamer❖ Capsudx Cool 3❖ Cool Strips❖ Glowspheres❖ Xanthan Gum❖ Mannitol❖ Corn StarchTechno Food Ingredients❖ Sucralose❖ Ethyl Cellulose

Thank You

Pls contact Ms. Seema Trivedi/Mr. Pratit Agarwal for any queries
Website: www.anshulindia.com
email add; seema.trivedi@anshulindia.com/;pratit.agarwal@anshulindia.com
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