Pharmaceutical compounding I - WordPress.com · 2017. 2. 14. · • Mechanical properties of...

University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Pharmaceutical Compounding

Pharmaceutical compounding I Colloidal and Surface-Chemical Aspects of Dosage

Forms

Dr. rer. nat. Rebaz H. Ali

2/13/2017 Pharmaceutical Compounding 2

Outlines

• Rheology

• Introduction

• Mechanical properties of solids

• Flow of liquids

• Newtonian liquids

• Non-Newtonian liquids

• Colloidal dispersions


Introduction

• Rheology is the branch of physics that deals with deformation and flow of matter.

• Deformation describes the change of matter in terms of shape or volume, or both.

• Increasing interest in rheological methods in the medical and biological sciences:

A. A change of the rheological behavior of certain body fluids such as mucus, saliva,

blood, or synovial fluid.

B. In pharmaceutics more viscous materials require larger amounts of energy during

mixing.

• The viscosity might be reduced by the application of heat, which could

reduce the mixing time and improve product homogeneity.

C. Patient compliance.

• Application of stiff creams

• Flow through a hypodermic needle,

• Pouring from bottle


• Rheology systems and stresses:

• Solids: have a constant volume and permanent shape, and are capable of

supporting loads.

• Liquids have constant volumes at constant temperature, variable shape, and

support no loads.

• Gases have neither constant volume nor permanent shape.

• Stress and Strain

• Deformation is the result of a force acting on or within a body, its extent depends on

the magnitude of force per unit area (F/A), i.e., the stress (Pa, Nm-2).

• As a consequence of the stress applied, the body will change its shape, and as a result,

there will be a change in length of the body, i.e., strain.

Introduction


Outlines

• Rheology

• Introduction


• Flow of liquids





Mechanical properties of solids

• Elastic solids are deform under stress, but once the stress is removed, they regain their

original shape, and the strain returns to zero.

• Point Y is the yield point or elastic limit, and the corresponding stress is the yield stress.

• If the stretching process of polyethylene or steel is

stopped before point Y, they will snap back to their

original length.

• Beyond Y, the solids undergo permanent deformation

from which they do not recover upon the removal of

stress, this called plasticity.

Stress, dyne/cm2

Pe

rce

nt é

lon

ga

tion

R

P G

S

Yield point

Breaking point


Mechanical properties of solids cont.

• Steel has a high modulus (young’s modulus E; it’s a characteristic property of solids,

representing their stiffness or hardness).

• 𝐸 = 𝑠𝑡𝑟𝑒𝑠𝑠

𝑠𝑡𝑟𝑎𝑖𝑛 =

𝐹/𝐴

∆𝑙

• The horizontal portion YAH, the material is

ductile; it flows under practically constant stress

like a viscous liquid.

• If the stress is released at A, the sample

retracts along AC. The nonrecoverable

deformation OC is called permanent set.

• R is the elongation at the break, and the stress

corresponding to B is the ultimate strength or

tensile strength.

B


Mechanical properties of solids cont

B

• The area OLYAHBRCO under the stress-strain

curve is the energy or work required to

break or rupture the material. It measures

the material’s toughness.

• Glass is hard and brittle.

• Steel is tough.

• Plastics are medium-hard or soft.


Outlines

• Rheology

• Introduction


• Flow of liquids





Flow of liquids

• Liquids do not retain their shape; the smallest

stresses, if applied for long enough time,

produce infinite deformation.

• If water and castor oil are poured from

bottles, water flows a thousand times faster,

i.e., its rate of shear is a thousand times

greater.

• γ =𝑉

𝐻=

𝑐𝑚

𝑠𝑒𝑐.𝑐𝑚= 𝑠𝑒𝑐−

• When liquid flows through a cylindrical tube

of small diameter the velocity is zero at the

wall of the tube, and maximum in the center.

H


Flow of liquids cont.

• Vasodilator drugs like nitroglycerin increase the radius of blood vessels by relaxing the

vascular smooth muscles.

• The viscosity of a fluid may be described simply as its resistance to flow or

movement. Thus water, which is easier to stir than syrup, is said to have the lower

viscosity.

• Viscosity η is defined as the ratio of shear stress τ to rate of shear γ.

• η = τγ

= 𝐹/𝐴

1/𝑠𝑒𝑐 =

𝑑𝑦𝑛𝑒/𝑐𝑚2

1/𝑠𝑒𝑐= Pa.s


Outlines

• Rheology

• Introduction


• Flow of liquids





Newtonian liquid

• The viscosity of simple liquids (i.e., pure liquids consisting of small molecules and

solutions where solute and solvent are small molecules) depends only on

composition, temperature, and pressure.

• It increases moderately with increasing pressure and markedly with decreasing

temperature.

• For solutions of solid solutes, the viscosity usually increases with concentration.

• When the viscosity is independent of the shear stress or the rate of shear, the

liquid called Newtonian liquid .


Newtonian liquid

• Plots of shear stress (on the y axis) as a function of the rate of shear (on the x axis) are

referred to as flow curves or rheograms.

• A has a higher viscosity than B because α > β

• The slope, f, is known as fluidity and is the reciprocal of viscosity, η:

Rheograms or flow curves of two Newtonian liquids.

Shea

r ra

te, S

-1

Shear stress, N/m2

B

A


Outlines

• Rheology

• Introduction


• Flow of liquids





Non-Newtonian liquid

A. Plasticity: the flocculated particles in concentrated suspensions do not flow at low

shear stresses (exhibiting reversible deformation like elastic solids) but flow like liquids

above their yield value (i.e., yield stress)

• This termed plastics or Bingham bodies.

• The more flocculated the suspension, the higher will be the yield value


Non-Newtonian liquid cont.

B. Shear-thinning Fluids. Many colloidal systems, especially polymer solutions and

flocculated solid/liquid dispersions, become more fluid the faster they are stirred.

• Shear-thinning behavior is often referred to as pseudoplasticity.

• Shear-thinning behavior is an example of non-Newtonian flow because the viscosity, at

constant temperature and composition, decreases with increasing shear.

• Examples are solutions of polymers, such as

MC or NaCMC and gums such as tragacanth

or acacia.



• The macromolecules tend to assume roughly

spherical shapes, which surrounded by a sheath

of water of hydration.

• The viscosity of the solution is reduced in these

ways:

• The polymer chain become elongated and

thus offer less resistance to flow.

• The amount of water trapped inside the

coils decreases.

• Brownian motion will lead to a rebuilding of

the inner structure in many cases



C. Dilatancy or shear-thickening is an increase in viscosity with increasing shear.

• It is shown by concentrated (> 50%) deflocculated dispersions as the amount of

liquid present is not much larger than that needed to fill the voids between the

particles

• As shear stress is increased the particles are rearranged which leads to a significant

increase in interparticle void volume.

• The amount of vehicle remains constant, accordingly, resistance to flow increases

because particles are no longer completely wetted, or lubricated, by the vehicle.

• Example is suspensions of starch in water.



• Thixotropy is the gradual decrease in viscosity with increased shear followed by a

gradual recovery of the original structure.

• Their apparent viscosity depends on temperature, composition, shear stress, and the

previous shear history and time under shear.

• It usually related to shear thinning materials.

• For shear thickening samples, called negative thixotropy.


Thank you for your attention!

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