Vztah mezi povrchovou energií vzorku a

mechanickými vlastnostmi tablet

How surface energy of powders affects tablet

properties

JAN PATERA

DEPARTMENT OF ORGANIC TECHNOLOGY, UCT PRAGUE

TABLET COMPRESSION WORKSHOP

25 -26 JANUARY 2017

What is Surface Energy

Why it is important to measure and how it can be measured

Examples of use of knowledge of Surface Energy

Introduction of surface energy

To quantify the ability of surface to react or interact

All systems try to reach their lowest energy levels

Introduction of surface energy

The surface energy is a very informative and important parameter of solids.

Knowledge of surface energetics is important in the formulation design of

multi-component systems and the prediction of processing performance.

Pharmaceuticals, Food products and ingredients, Coatings and thin films, Cosmetics

and personal care products, Flavourings and perfumers, Natural and artificial fibers,

Biopolymers etc.

Ability to measure the surface energy of various materials is essential for

ensuring compatibility between the given base material and the top coating

one wishes to apply onto it or other materials one wishes to attach to it.

Pharmaceutical powders

Pharmaceutical powders

Tablet strength is controlled by formation of intermolecular forces over the areas of contact between the particles. The strength of these bonding forces is controlled by surface energy.

Knowledge of the wettability and surface energy of pharmaceutical solids is important in the design of pharmaceutical formulations.

Materials with high surface energy are easier to wet and adhere to than those with low surface energy.

If the surface energies of the individual compounds are known, the work of adhesion or cohesion can be obtained.

D.M. Parikh: An overview of the properties of pharmaceutical powders and their effects on

processibility. Am. Pharm. Soc. (2006)

Relationship with other properties

A.Kondor: Understanding surface energy. SMS seminar, Prague, 2015

Relationship with other properties

A.Kondor: Understanding surface energy. SMS seminar, Prague, 2015

How to measure Surface energy

Inverse Gas

Chromatography

(IGC)

IGC is the most commonly successfully used technique

for surface energy analysis of powders and fibers

Inverse gas chromatography

Gas phase sorption technique

Inverse gas chromatography (IGC) principles developed in 1950s. 1

Focus of physicochemical studies on the kinetic information and thermodynamic quantities from sorption equilibria.

Earlier work for catalytic materials, e.g. Activated carbon, alumina, silica etc.

Powerful physicochemical characterization tool for powders, fibers, films, particulates, semi-solids.

1st development of IGC for surface energy and acid/base interactions was for polymers and composite materials.2

1) R.J.Laub and R.L. Pecsok: Physicochemical Applications of gas chromatography. New York, John Wiley and sons. 1978

2) J. Schultz, L. Lavielle and C. Martin: The role of the interface in carbon fiber epoxy composites. J. Adhesion, 1987

Principles of iGC

Slope

Injection Column Response

Sample GC column Peaks

GC

IGC

Probe Sample Peak of the probe

Dvstechnique:

https://commons.wikimedia.org/wiki/File%3AAnalytical_Gas_Chromatography_A.gif

Surface energy components according to Fowkes:

Dispersive component – physical long range interactions (London) measure by serie of unpolar

solvents

Lewis acid-base component – chemical short range interactions measured by at least two mono-

functional polar solvents

Modification of surface energy

milling,

A.Kondor: Understanding surface energy. SMS seminar, Prague, 2015

Formulation design of multicomponent systems

Systems consists of two or more individual components

Pharmaceuticals (Drugs + Excipients), Foods etc.

The performance of a dosage form is linked to the physical and chemical properties of all ingredients within the formulation.

Thermodynamic parameters can be used to understand how solid surfaces interact:

With each other cohesion

With vapors (e.g. Moisture)

With liquids (e.g. Solvents) adhesion

With other solid surfaces

Importance of Adhesion/Cohesion for powders,

fibers etc.

Typical examples:

Surface modification, e.g.

Coatings

Processing, e.g. Milling,

granulation

Dry powder inhalation

Changes in surface energetics

with milling

0

50

100

150

200

250

300

350

0 5 10 15 20 25 30

c [m

g.l-1

]

t [min]

API A

0

30

60

90

120

150

180

0 5 10 15 20 25 30

c [m

g.l-1

]

t [min]

API B

API A 33,87

API B 37,96

API B (milled) 44,39

Influence of the surface energy on the dissolution of multicomponent tablets

Cohesion of the more energetic particles influences

dissolution of API from mixtures

Particles with lower surface energy dissolve faster

due to the weaker interactions

API A + API B (milled) API A + API B

Influence of the SE and size of the components on its dissolution from tablets

0

50

100

150

200

250

300

350

0 5 10 15 20 25 30

c [m

g.l-1

]

t [min]

API A

0

30

60

90

120

150

0 5 10 15 20 25 30

c [m

g.l-1

]

t [min]

API B

Cohesion of the more energetic particles influences

dissolution of API from mixtures

Larger particles with smaller surface area dissolve

faster due to the weaker interactions

API A 100 33,87

API B 2 188 44,39

API B 3 338 40,75

API A + API B 2 API A + API B 3

Mean particle size [mm]

Surface energy heterogeneity

M. Naderi: The Assessment of the Surface Chemistry and Thermodynamic Properties of Solids by IGC-SEA, London, 2016

Flowability – Energy as a function of aeration

Silanisation influences the dynamic flowproperties – free flowing powder workadhesion – easy flow over stainless steelsurfaces.

M. Naderi: The Assessment of the Surface Chemistry and Thermodynamic Properties of Solids by IGC-SEA, London, 2016

Dissolution rate and tablet strength

0

2

4

6

8

10

12

14

0 10 20 30

Co

nce

ntr

atio

n o

f A

PI

(mg

/l)

Time (min)

0

20

40

60

80

100

600 700 800

Cru

shin

g st

ren

gth

(N

)

Compaction force (kg)

Batch λ (mJ m−2)

A 38,45

B 41,83

• Dissolution profile of „batch B“ influenced with higher value of SEleads to better wettability of the surface.

• Tablet strength higher with more cohesive materials with higher SE.

Viscoelastic parameters of particulates

• Strong dependence between elasticity and surface energy of granulates

• Influence of SE on the dependence of Plasticity with changing compaction force• Higher SE leads to cohesion of the particles and stronger influence of the compaction force

70

75

80

85

90

80 100 120 140 160

Pla

stic

ity

Compaction force (kg)

Batch A Batch B

6,5

7

7,5

8

8,5

9

36 38 40 42 44 46 48

Elas

tici

ty

Surface Energy (mJ/m2)

Batch λ (mJ m−2)

A 38,45

B 41,83

Acknowledgement

Assoc. Prof. Petr Zámostný, my graduate students and

colleagues from Department of Organic technology at UCT

Anett Kondor and coll. from Surface Measurement Systems Inc.