Improved and Novel Excipients – Need, sources of new excipients-co-processing and particle engineering, benefits of co-processed excipients, characterization, examples, regulatory aspects

1. Improved and
Novel (new)
Excipients

2. Source of new excipients development
There are three ways by which new excipients could be developed
• Using new chemical entities as excipients
• Develop new grades of existing excipients
• Develop new combinations of existing excipients

3. New and novel excipients
Excipients are used in almost all approved drug products and are
essential to the performance of the formulation. New and novel
excipients include some of the following examples:-
• Natural polymers
• Natural polymers modified with synthetic polymers
• Synthetic polymers
• Synthetic polymers modified with small molecules or other
combinations
• Co-processed excipients

4. Co-processed excipients
• Coprocessing is a novel concept of processing two or more
established excipients (parent excipients) by some appropriate means
to retain and improve the favorable attributes of functionality and
mask the undesirable properties of parent excipients
• The functionality can be in terms of improved process ability such as
flow properties, compressibility, content uniformity, dilution
potential, and lubricant sensitivity, or improved performance such as
disintegration and dissolution profile.

5. Need for novel excipients
Challenges in formulation development represent a need for new
excipients. Some of these challenges include the following:
• Demand for ideal filler-binder for direct compression manufacturing
process for tablets
• Increased speed of tablet machines and manufacturing efficiency
drives demand for excipients with good compressibility and low
weight variation at shorter dwell times
• Overcome loss of compaction with wet granulation and high moisture
sensitivity
• Need to modulate solubility, permeability, and stability of drug
substances.

6. Particle engineering for developing new
excipients
• The fundamental particle properties (such as shape, size, size
distribution, surface morphology, surface area, and porosity) have a
direct impact on excipient functionalities such as rate of dilution,
disintegration, and lubrication.
• Hence, the creation of a new excipient must begin with the particle
design which can give desired functionalities
• Particles with unique characteristics can be created by controlling the
conditions of crystallization and drying processes
• E.g. there are two grades of Micro crystalline cellulose (MCC)—Avicel®
PH-101 and -102

7. Coprocessing method
Identification of
parent excipients
(on basis of material
characteristics and required
functionality)
Selection of
proportion of
excipients
Assessment of
functionality (e.g.
flow property)
Selection of drying
processes (e.g.
spray drying)
Optimization of
variables to achieve
desired
functionality

8. Particle property and functionality

9. Levels of solid
state

10. Material characteristics in coprocessing
• Material science plays a significant role in altering the
physicomechanical characteristics of excipients, especially with regard
to their compression and flow behavior
• Solid materials, by virtue of their response to applied mechanical
force, can be classified under the following three heads
• Elastic: Any change in shape is completely reversible, and the material returns
to its original shape upon release of applied stress.
• Plastic: Permanent change in the shape of a material due to applied stress,
e.g., MCC, corn starch, and sodium chloride.
• Brittle: Rapid propagation of a crack throughout the material on application
of stress, e.g., sucrose, mannitol, sodium citrate, lactose, and dicalcium
phosphate

11. Material
classification on
the basis of their
deformation
behavior in the
presence of
applied force

12. Benefits of co-processed excipients
1. Improved Flow Properties
2. Improved Compressibility
3. Better Dilution Potential
4. Reduced Lubricant Sensitivity
5. Multiple Advantages

13. 1. Improved Flow Properties
• Controlled optimal particle size and size distribution ensures superior
flow properties of co-processed excipients and reduced reliance on
addition of glidants.
• The spray-dried coprocessed product had a spherical shape and even
surfaces, which resulted in improved flow properties
• E.g. Tablets prepared with M80K, a co-processed cellulose powder
with crystalline solid dispersion CSD, showed lesser weight variation
than those prepared with Avicel

14. 2. Improved Compressibility
• Coprocessed excipients have been mainly used in direct compression
(DC) tableting because of their better flow ability and compressibility,
and the excipient formed is a filler-binder.
• The compressibility of several coprocessed excipients such as
Cellactose® have been reported to be superior to the physical
mixtures of their constituent excipients (alpha-Lactose-monohydrate
and powdered cellulose).

15. 3. Better Dilution Potential
• Dilution potential is the ability of the excipient to retain its
functionality even after dilution with another material in a finite
proportion.
• Most drug substances are poorly compressible, and require excipients
to achieve better compressibility to retain good compaction even on
dilution with them.
• Cellactose® has been shown to possess a higher dilution potential
than a physical mixture of its constituent excipients

16. 4. Reduced Lubricant Sensitivity
• Coprocessing impart lesser sensitivity of the product toward loss of their
functionality in the presence of lubricants.
• Most coprocessed products consist of a relatively large amount of brittle
material such as a-lactose monohydrate and a smaller amount of plastic
material such as cellulose.
• The plastic material provides good bonding properties by creating a
continuous matrix with a large surface for bonding.
• The large amount of brittle material provides low lubricant sensitivity by
preventing the formation of a coherent lubricant network by forming newly
exposed surfaces upon compression, thus breaking up the lubricant
network.

17. 5. Multiple Advantages and other benifits
• Provide a single excipient with multiple functionalities, thereby
reducing the inventory burden
• Reduce product cost due to improved functionality and fewer test
requirements compared with individual excipients
• Coprocessing of mannitol with sorbitol resulted in interlocked crystals
with stronger binding capacity. Provide more robust tablets at low
compression force
• Compressible powder was obtained by spraying a 4.5% aqueous
solution of poly(vinyl pyrrolidone) (PVP) onto a fluid bed of starch and
PVP admixture (48:1)

18. Regulatory aspects in development of novel excipients
• It is important to recognize potential use of new excipient in various
drug delivery systems.
• The major obstacle to the success of coprocessed excipients in the
marketplace is their non-inclusion in official monographs
• The International Pharmaceutical Excipients Council of the Americas
(IPEC-Americas) provide guidelines for evaluations of new
pharmaceutical excipients.
• The IPEC’s New Excipient Safety Evaluation procedure provides method
for evaluating the safety of new excipients including co-processed
excipients.
• The excipient sponsor can use the NEEC’s report to support the use of a
new excipient in a drug development approval process

19. Supporting data needed for novel excipient

20. Three main areas to
be controlled for
total excipient
control (TEC)
system

21. References
• Saha, S., & Shahiwala, A. F.,Multifunctional coprocessed excipients for
improved tabletting performance . Expert Opinion on Drug Delivery ,
6 (2), 2009.
• Kadtare A. and Mahesh Chaube, Excipient Development for
Pharmaceutical, Biotechnology and Drug Delivery Systems, Informa
Healthcare USA, Inc. 270 Madison Avenue, New York 10016, 2006
• Otilia m. Y. Koo, Pharmaceutical excipients : properties, functionality,
and applications in research and industry

22. Thank You