Purpose of the present review is to provide an in depth knowledge on recent developments in excipients preparation, technology and approaches involved in their formation and development. Excipients play an important role in dosage form development. In conventional formulation of dosage forms, each excipient is used to provide its required function/performance. Presently, excipient manufacturers have focused their attention on producing a multifunctional excipients with improvement in their performance and quality of dosage form. Manipulation in the functionality of excipient is provided by the co-processing of two or more existing excipients.

1. PRESENTED BY :
MEET DETROJA
AELISH BHUVA
B. PHARM
GUIDED BY :
DR.YAMINI D. SHAH
HOD, DEPT. OF PHARMACEUTICS
CO–PROCESSED EXCIPIENTS FOR TABLETS

2. CONTENT
1. Introduction of excipient 9.Evalution parameters
2. Function classification of excipient 10.Regulatory perspective
3. Need for co-processing 11.Example of marketed co-processed excipient
4. Co-processed excipient 12. References
5. Principle of co-processing
6. Excipient selection criteria
7. Step involved in co-processing
8. Method of co-processing

3. AIM:
• To review on co-processed excipients and recent update in their commercial production and application in manufacture of
tablets.
RATIONALE
• Improve flowability
• Improve compressibility
• Used direct compression method for tableting
• Decrease disintegration time
• Single excipient provide multifunctionality

4. INTRODUCTION OF EXCIPIENT
Definition
The International Pharmaceutical Excipients council(IPEC) defines excipients as substances other than the API which
are present in the dosage forms or medicines .
Property of excipient
• Physiologically inert.
• Physico-chemically stable
• Free from microorganisms.
• Should not interfere with the bioavailability of the drug
• Low cost, inexpensive.
• Meet the standards of regulatory requirements

5. FUNCTIONAL CLASSIFICATION OF EXCIPIENT
1. Diluents
2. Binders or granulating agents
3. Disintigrating agents
4. Lubricating agents
5. Glidants
6. Antiadherants
7. Organolaptic additives
- Colouring agents
- Flavouring agents
- Sweetening agents
- Adsorbents
- Preservatives

6. NEED FOR CO-PROCESSED EXCIPIENT
• Step involved in different types of tablet manufacturing processes:
Step Direct compression Dry granulation Wet graduation
1 Blending /mixing of API and excipients Blending /mixing of API and excipients Blending /mixing of API and excipients
2 Compression Compression into slugs Preparation of binder solution
3 Size reduction of slugs and sieving Massing of binder solution of step 2 with
powder mixture of step 1
4 Mixing of granules with excipients Wet screening of damp mass
5 Compression Drying of wet granules
6 Resifting of dried granules and blending
with excipient
7 Compression

7. Conclusion: Direct compression requires fewer processing steps, simplified validation, elimination of heat and
moisture, economy, and improved drug stability compared with wet/ dry granulation technique.
Idel requirements for direct compression excipients :-
• Free flowability
• High compreseibility
• Better dilution potential
• Re-workability
LIMITATION- There are only few excipients which exhibits all the ideal characteristics required for direct
compression.
Excipients with improved functionality can be obtained by:
1.developing new chemical excipients:- costly, regulatory requirements
2.new combination of existing materials:- interesting option,done by co-processing process

8. CO-PROCESSED EXCIPIENTS
DEFINITION
Co-processed excipients are combination of two or more excipients designed to physically modify their
properties in a manner not achievable by simple physical mixing and without significant chemical change.
1980 -- MCC with calcium Carbonate.
Advantages
• Single excipient provide multiple function
• Improve flow properties
• Improve Compressibility
• Decrease disintegration time
• Decrease weight variations during tablet manufacturing
• Improve hardness of tablet
• Better mouth feel and improved palatability
Disadvantages
• Time consuming process
• Loss of material during various stages of processing
• Expensive due to factor such as labour, space, time, special equipment and energy requirement.

9. PRINCIPLE : PARTICLE ENGINEERING
BULK LEVEL
Flow property, Compreseibility,
Hygroscopicity, bulk density
MOLECULAR LEVEL
Crystalline ( Polymorphic,
Pseudopolymorphic)
PARTICLE LEVEL
Particle surface, Particle size and distribution
Surface area, Porosity, surface morphology

10. Particle property Function
Enlargement of particle size
Increase particle porosity Solubility, flowability,
compressibility
Particle size distribution Segregation potency
Surface roughness Flowability, segregation potency
Flowability, compressibility
Particle properties influencing Excipient functionality

11. Excipients Selection Criteria in Co-Processing
Selected excipients must be compatible and inert with each other. Co-processing is generally done
by one excipient which is plastic in nature and another one is brittle in nature. For optimum tableting
performance combination of both excipients are mandatory. It is reported by the researchers that the
co-processing done with a large amount of brittle excipient and a small amount of plastic
excipient. This particular combination of excipients prevent storage of large amount of elastic energy during
compression, which results in a limited amount of stress relaxation and reduced tendency of capping and
lamination.
Ex. Lactose(75%) –brittle excipient
Cellactose
Cellulose- 25% -plastic excipient

12. Step involved in co-processing
1.Preliminary study on excipients to be selected for co-processing in order to
study their characteristics and functionalities.
2.Determine their ratio to be used for co-processing.
3.Study particle size distribution of each excipient to be co-processed.
4.out of a available technique, select the most suitable one for co-processing.

13. METHODS FOR CO-PROCESSING
1.SPRAY DRYING
• Fluid state (Solution, suspension, Dispersion or emulsion)
• Factor to be considered:physical and chemical characteristics of individual excipient, design of the equipment used , spray
drying inlet air temperature, atomization air pressure, rate of initial inlet, viscosity of the fluid, percent of solid present in the
feed, rpm of disc.
• Ex. of spray-dried co-processed excipient: 30%MCC, 25% lactose, and 45% starcap - added to distiled water - mixing using
magnetic stirrer - homogenous suspension - drying by spray dryer
Set process parameters- Inlet air temperature- 190°C, Feed rate- 4ml/min
Atomization pressure- 2 bar
Result- obtain spherical shape particle improve flowability and compressibility of poor compreseible drug like Etodolac.
(SI C, SV N, MM S, JR C. Development and Characterization of Multifunctional Directly Compressible Co-processed Excipient by
Spray Drying Method. AAPS PharmSciTech [Internet]. 2017 May 1 [cited 2021 Oct 16];18(4):1293–301. )
Dried powder, agglomerate
or granular form

14. 2.ROLLER COMPACTION
In this system uniform powder of the excipients to be co-processed is compacted between counter rotating rollers to
form ribbon of compacted material that is then processed into granules. Roller compaction is suitable for co-processing of
moisture or high temperature sensitive excipients because there is no drying.
Ex:- Polyethylene oxide and Hydroxyl Propyl methyl cellulose polymers were accurately weighed as per specified Ratio (7:3)
and mixed for 10 min to form uniform blend. These blends were used for compaction using roller compactor (Clit roller
compactor, India). The obtained ribbons were screened through 40# and 60# sieve. The obtained fine powder was further
recycled to get granules of uniform Size. This granules used for tableting.
Result: co-proceseed excipient have better flowability and compressibility than their individual or physical mixture.
(Avinash Gangurde, Rahul kasinath patole. Ajay Kumar Sav. A novel directly Compressible Co-processed
excipient for sustained release formulation. Journal of Applied pharmaceutical Sciences vol 3 )

15. 3.CRYSTALLIZATION
In this method prepare the solution of excipients at the supersaturated conditions. This means that solution contain more
amount of solute than saturated solution. From the solution crystal are achieved by different method like (1) solution
cooling, (2) addition of a second solvent to reduce the solubility of the solute(3) Chemical reaction and (4) change in ph.
Then crystal are separated from the solvent by filtration and dry them.
Ex.:-Direct compacting and tableting sugar Di-Pac is manufacturing by crystallization method by Domino sugar industry, and
contain sucrose (97%) and maltodextrin (3%).
Result: co-processed material Di-Pac has a direct compacting property, better flow property, low hygroscopicity and low
moisture content (LOD <1%) , it prevent degradation of API. Di-Pac is a readily soluble, it effect on the solubility of the
active ingredients and reduces the need for disintegrants.
(Jivraj, M., Martini, L. G., and Thomson, C. M., An Overview of the Different Excipients Useful for the Direct Compression of
Tablets, PSTT, 3: 58-63, 2000)

16. 4.MILLING
Milling or dry grinding for the production of co-processed excipients may be carried out in a roller mill, a ball mill, a bead mill, a
millstone mill, a jet mill, and a hammer mill.
Ex. :-Ball milling has been adopted by Rao For co-processing of cross-linked polyvinylpyrrolidone and calcium silicate. In this
particular case, ball mill was operated for hours at a speed of 200 rpm using 25 stainless steel balls.
Result:co- processed Excipient of cross-linked polyvinylpyrrolidone and calcium silicate enhances the rate and extent of dissolution of
poorly soluble drug.
(Rao VU , Balasubramaniam J, Haldar RK. Coprocessed excipient compositions. US20120178822, 2012)

17. EVALUATION PARAMETERS
precompression parameters.
• Bulk density
• Tapped density Table- flow characteristics as per evaluation parameters
• Hausner's ratio
• Compressibility index
• Angle of repose
• No chemical changes
Flow characteristics Angle of repose Carr's index Hausner’s ratio
Excellent 25-30 ≤10 1-1.11
Good 31-35 11-15 1.12-1.18
Fair 36-40 16-20 1.19-1.25
Passable 41-45 21-25 1.26-1.34
Poor 46-55 26-31 1.35-1.45
Very poor 56-65 32-37 1.46-1.59
Very very poor >66 >38 >1.60

18. Post compression parameters
• Weight variation test:Uniformity in the weight of tablet can be checked by weight variation test.
• Hardness test: ( ‘ crushing strength test ‘). Tablets require a certain amount of strength or hardness to withstand mechanical shocks of
handling in manufacture, packaging and shipping. Tablet hardness id defined as the ‘force required for breaking a tablet'. It is expressed in the
kg/cm².
Factor affecting to hardness: Force provide for the compression, Moisture content , Binder concentration
Equipment : Monsanto hardness tester, Pfizer hardness tester , Strong cobb hardness tester
Official standard for hardness: 4-8 kg/cm²
Sr
no.
Average weight of tablet % weight variation
acceptance (+or-)
1 84 or less mg 10%
2 84-250 mg 7.5%
3 >250 mg 5%

19. • Friability test:Physical strength of uncoated tablet upon exposure to mechanical shock and attrition can be determine by the
friability test. It is usually measure by Roche friabilator.
Standard for friability:- % friability should be up to 0.5 to 1 % for compressed tablets
%friability=Wi-Wf/Wi x 100
• Disintegration test:Disintegration is a process in which tablets are break up into granules or smaller particles once the tablet is
exposed to the gastric fluid.
Official standard for disintegration time as per I. P.: Uncoated compressed tablets-15 min, Sugar coated tablet-60 min
Film coated tables -30min Enteric coated tablet-60 min

20. • Dissolution test:When a dosage form is swallowed in the gastric fluid, the rate at which it releases the active ingredient is
critical to ensure that the drug is delivered properly. The rate at which the drug is released is called the dissolution rate.
• List of dissolution apparatus as per U. S. P. Type of dissolution apparatus as per I. P.
Type 1-Basket type apparatus Type 1-Paddle apparatus
Type 2-Paddle apparatus Type 2-Basket type apparatus
Type 3-Reciprocating cylinder
Type 4-Flow through cell Standard as per U. S. P. :75% of drug should be dissolved within 45 min
Type 5-Paddle over disk
Type 6- Rotating cylinder
Type 7- Reciprocating holder

21. Explaination of co-processing based on the results of evaluation parameters
Simple Lactose excipient
-precompression parameters -post compression parameters
Carr’s index-31.03 -Very poor compressibility because of less compression of
Hausner’s ratio- 1.45-poor flowability Lactose tablets are not formed
Co-procrssing of lactose: PVP:Crospovidone (87:10:3) by solvent evaporation method.
-precompression parameters -post compression parameters
Carr’s index-18.23 – fair Compreseibility Hardness-3. 7kg
Hausner’s rational-1. 203- fair flow property friability- 0.51%
• (Mahesh gattani, Vinay singh, Manish shukla . Development of directly compressible co-processed excipients for orally
disintegrating tablets using rotary evaporation method. International journal of pharmacy and pharmaceutical science
0975-1491.)

22. What are the regulatory perspective required for
the co-processed excipient?

23. EXAMPLE OF MARKETED CO-PROCESSED EXCIPIENT
Co-process excipient Trade name Advantages Company name Method name
Lactose,25% cellulose Cellactose High compressibility, good
mouthfeel
Meggle pharma Spray drying
Sucrose,3 % Dextrin Dipac Use for direct compressible
tablet, improve flowability.
Seppic pharma Crystallization
Lactose,3.2%Kollidon 30 Ludipress Good flowability, tablet
hardness
Basf pharma Spray drying
95% β lactose, 5% lactitol Pharmatose
dcl 40
High compresiibility Dfe pharma Spray drying
Starch 15 %, lactose 85% Starlac Good flow property, high
Compressibility
Meggle pharma Spray drying
Microcrytalline cellulose,
lactose
Microcelac Capable of formulating high
dose, good flowability
Meggle pharma Wet granulation method

24. REFERENCES:
1. Gangurde A, Kashinath Patole R, Kumar Sav A, Amin D. A Novel Directly Compressible Co-Processed Excipient for
Sustained Release Formulation. J Appl Pharm Sci [Internet]. 2013 [cited 2021 Oct 16];3(09):89–097. Available
from: http://www.japsonline.com
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EXCIPIENTS. Pharm Reson. 2019;2:1.
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4. Gohel MC, Jogani PD, Bariya SH. Development of agglomerated Directly compressible diluent consisting of brittle and
ductile Materials. Pharm Dev Technol 2003;8:143–51.
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Entities. International Journal of Pharmaceutical and chemical sciences, 1(4), pp.1480-1498
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in Pharmaceutical Research LJCTPR, 2013: Vol. 1(3): 205-214

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