Colloidal dosage Forms - · PDF fileUniversity of Sulaimani School of Pharmacy Dept. of...

University of Sulaimani School of Pharmacy

Dept. of PharmaceuticsThird level - Second semester

Colloidal dosage Forms

Dr. rer. nat. Rebaz H. Ali

4/3/2017 Pharmaceutical Compounding 2

Outlines

• Disperse systems

• Introduction

• Lyophilic

• Lyophobic

• Gels

• Aerosols

• Association colloid

• Micelles

• Pharmaceutical application of colloidal system


Introduction

• Dispersion system consist of at least two phases: one or more dispersed or

internal phases, and a continuous or external phase called the dispersion medium or

vehicle.

• Colloidal dispersions can be characterized as containing particles in the size range of

between approximately 1 nm and 1 micrometer, e.g. blood, milk, micelles and etc.

• sol is a general term which means dispersion of a colloidal solid substance in a

liquid, or gaseous medium

• Hydrosol, alcosol, and aerosol


Category Particle Size Characteristics Examples

Molecular solution of small molecules and ions

< 10 Ao

• lower limit of resolution by electron microscope• high rates of diffusion• pass through filter paper, ultra filter and dialysis

membranes• high osmotic pressure

NaCl, sucrose in water

Colloidal dispersions

10 Ao - 1μm

• Visible in electron microscope and invisible in ordinary microscope

• low rate of diffusion• undergo Brownian motion• pass through filter paper, retained by ultrafilter and

dialysis membranes• low osmotic pressure.

Bacterial and virus suspension, sod. CMC in water, surfactant micelles

Coarse dispersion > 1μ

• Visible in ordinary microscope• retained by filter paper• no diffusion no Brownian motion• settle out or cream• negligible osmotic pressure

Most pharmaceutical suspension and emulsions.

Introduction cont.


Diffusion and sedimentation

• The continuous motion of the colloidal particles causing collisions and the random

bombardment imparts and erratic movement called brownian motion.

• Brownian motion prevents sedimentation

• A common measure of the mobility of a dissolved molecule or suspended particle in a

liquid medium is the diffusion coefficient.

• 𝐷 =𝑅𝑇

6πη𝑟𝑁

• As particle size or r increases, brownian motion decreases.

• With increased vehicle viscosity, the diffusion coefficients are decreased.


Outlines


• Introduction

• Lyophilic

• Lyophobic

• Gels

• Aerosols


• Micelles



Lyophilic dispersions

A. lyophilic Dispersions

• The system is said to be lyophilic (solvent-loving) if there is considerable

attraction between the dispersed phase and the liquid vehicle .

• Due to the presence of high concentrations of hydrophilic groups, solids swell,

disperse, or dissolve spontaneously in water.

• Hydrophilic colloidal dispersions can be further subdivided as:

• True solutions: water-soluble polymers (e.g., acacia).

• Gelled solutions:

• Particulate dispersions: solids remain as discrete though minute particles (e.g.,

bentonite).


The electrical double layer

• The surface charge influences the distribution of ions in the aqueous medium

• Ions of opposite charge to that of the surface, termed counter-ions, are attracted

towards the surface i

• Ions of like charge, termed co-ions,

are repelled away from the surface.

• Zeta potential is a property of an

electric structure that is usually built

up at interfaces i.e. double layer.

• Higher the zeta-potential, the more

stable the colloid.

• When the zeta-potential equals zero,

the colloid will precipitate into a solid.


The electrical double layer cont.

• Due to Brownian motion, the colloidal particle collision whether result in permanent

contact of the particles (coagulation) the particles rebound and remain freely

dispersed.

• These forces can be divided into three groups:

• Electrical forces of repulsion

• Forces of attraction

• Forces arising from solvation.

• Aggregation is a general term signifying the collection of particles into groups.

• Coagulation signifies that the particles are closely aggregated and difficult to

redisperse.


Outlines


• Introduction

• Lyophilic

• Lyophobic

• Gels

• Aerosols


• Micelles



B. Lyophobic dispersion

• Lyophobic (solvent-hating) dispersions are unstable and irreversible because of the lack

of attraction between the dispersed and continuous phases.

• The van der Waals attractive forces between the particles are stronger than the

solvation forces, therefore, the particles tend to aggregate.

• The dispersed phase is coalesced into large drops.

• Examples of materials that form hydrophobic dispersions cholesterol, sulfur, paraffin

wax and etc.


Outlines


• Introduction

• Lyophilic

• Lyophobic

• Gels

• Aerosols


• Micelles



Gels

• Gels (jellies) are semisolid systems consisting of dispersions colloidal particles in an

aqueous liquid vehicle.

• The particles link together to form a network, thus imparting rigidity to the structure.

• The flexible chains of dissolved polymers interpenetrate and entangle because of

the constant brownian motion of their segments.

• Each chain is encased in a sheath of solvent molecules that solvate its functional

groups.

• Gels are more rigid than jellies because gels contain more covalent crosslinks, a higher

density of physical bonds, or simply less liquid.

• Gels either single-phase or two-phase (magma)


Gels

• Imbibition is the taking up of a certain amount of liquid without a measurable

increase in volume.

• Swelling is the taking up of a liquid by a gel with an increase in volume.

• Syneresis occurs when the interaction between particles of the dispersed phase

becomes so great that on standing, the dispersing medium is squeezed out in

droplets and the gel shrinks.

• Xerogel is the removing of the liquid remaining only the gel framework


Classification

According to the dispersion

• Gelation of lyophobic sols

• Gelation of lyophilic sols

• Chemical

• Physical


Gelation of lyophobic sols

• Clays such as bentonite, aluminium magnesium silicate (Veegum) and kaolin form

gels by flocculation.

• The forces holding the particles together in this type of gel are relatively weak – van

der Waals forces.

• They show phenomena of thixotropy.

• If a thixotropic gel is sheared these weak bonds are broken and a lyophobic sol is

formed.

• This phenomenon of thixotropy is employed in the formulation of pharmaceutical

suspensions, e.g. bentonite in calamine lotion.


Gelation of lyophilic sols

Type I Type II

• Chemical gel

• The interaction between the polymerchains is covalent and is mediated bymolecules that cross-link the adjacentchains

• Irreversible

• Physical gel

• Hydrogen bonds and van der Waals interactions maintain the gel network

• Reversible

Polymer chains

Cross links

Polymer chainsJunction

zones


Examples

• Natural polymers include polysaccharides (acacia, agar, pectin, sodium alginate,

tragacanth, xanthan gum) and polypeptides (gelatin).

• Cellulose derivatives are produced by chemically modifying cellulose.

• MC, NaCMC, HEC, HPC, and HPMC.

• Water-soluble synthetic polymer: PEG, PEO, PVP, and carbomer.

Cellulose


Outlines


• Introduction

• Lyophilic

• Lyophobic

• Gels

• Aerosols


• Micelles



Aerosol

• Pharmaceutical aerosols are pressurized dosage forms that, upon actuation, emit a

fine dispersion of liquid and/or solid materials containing one or more active

ingredients in a gaseous medium.

• They differ from most other dosage forms in their dependence upon the function of

the container (valve assembly), and an added component (the propellant).

• They ay be designed to expel their contents as a fine mist; a coarse, wet, or dry solid

particles; foam.


Aerosol cont.

• Medicated or cosmetic aerosol could be used by

• Inhalation

• In inhalation aerosol, degree of respiratory penetration depends on the particle

size.

• Topically (skin, vaginal or rectal)


Aerosol cont.

• Aerosols used to provide an airborne mist are termed space sprays.

• Room disinfectants and room deodorizers

• The particle size of the released product is generally quite small

• Aerosols intended to carry the active ingredient to a surface are termed surface

sprays or surface coatings.

• Deodorant, perfumes, paint spray and etc.


Aerosol formulation

• An aerosol formulation consists of two component parts: the product concentrate

and the propellant.

• Product concentrate is the active ingredient of the aerosol combined with the

required adjuncts

• The propellant is a liquefied gas like chlorofluorocarbons

• Dichlorodifluoromethane or dichlorotetrafluoroethane

• Or compressed gases

• Carbon dioxide, nitrogen, and nitrous oxide.


Valve assembly

• The function of the valve assembly is to permit expulsion of the contents of the can

in the desired form, at the desired rate, and in the case of metered valves, in the

proper amount or dose.


Outlines


• Introduction

• Lyophilic

• Lyophobic

• Gels

• Aerosols


• Micelles



C. Association Colloids

• Organic compounds that contain large hydrophobic moieties on the same

molecule with strongly hydrophilic groups are said to be amphiphilic.

• The individual molecules are generally too small to be in the colloidal size range, but

they tend to associate into larger aggregates when dissolved in water or oil.

• Surfactant (called surface active agents and associated colloid), are compounds which,

is soluble in a given a liquid and adsorbed at its interfaces.

Hydrophilic hydrophobic

• If the surfactant molecule contains ions, it

is classified as ionic otherwise the

surfactant is said to be non-ionic


C. Association Colloids cont.

• Anionic surfactant

• Soaps are the oldest surfactants, it is the sodium or potassium salt of lauric or oleic

acid.

• The bile salts sodium glycocholate and sodium taurocholate emulsify triglyceride in the

intestine and solubilize monoglycerides.

• Cationic surfactants:

• These are quaternary ammonium compounds,

• They have bacteriostatic activity

• Examples are ceylpyridinium chloride, benzalkonium chloride.


C. Association Colloids cont.

• Amphoteric agents

• They are containing carboxylate or phosphate groups such as the anion, and amino or

quaternary ammonium groups such as the cation, e.g. phosphatidylcholine (lecithin).

• Non ionic surfactant

• These surfactants do not have any charge. E.g. sorbitan ester (Span), polysorbate

(Tween) and poloxamer.

Sorbitan monoester Polyethoxylated monosester


Outlines

• Rheology

• Surface and interfacial tension

• Colloidal dispersions

• Gel formation

• Micelles



Micelles

• As the surfactant concentration in a liquid is increased, the amount of the surfactant

adsorbed at the liquid-air and liquid interfaces increases and these interfaces

become crowded.

• At a given concentration and temperature all micelles of a given surfactant usually

contain the same number of molecules (25 to 100).

• The diameters of micelles are approximately between 30 to 80 Ao.

• The lowest concentration at which micelles first appear is called the critical micelle

concentration.


Micelles cont.

• The number or concentration of micelles increases proportionally with the total

surfactant concentration.

• Micelles formed in dilute aqueous solutions are approximately spherical.

• In more concentrated aqueous solutions of surfactants, micelles change from spherical

either to cylindrical or lamellar shapes.


Critical micelle concentration

Solubility

Surface tension

Interfacial tension

Osmotic pressure

Equivalent conductivity


Outlines

• Rheology

• Surface and interfacial tension

• Colloidal dispersions

• Gel formation

• Micelles



Pharmaceutical application of colloidal systems

• Microemulsion

• Microemulsions are liquid dispersions of water and oil that are made homogeneous,

transparent, and stable by the addition of relatively large amounts of a surfactant and a

co-surfactant.

• Microemulsion droplets have a mean diameter range of approximately 6 to 100 nm.

• Microemulsions require a co-surfactant (linear alcohol).

• The advantage of microemulsions

• Smaller droplet size, which increases drug release,

• superior physical stability.

Microemulsions Emulsion


Pharmaceutical application of colloidal systems

• Liposomes

• Liposomes are synthetic spherical vesicles consisting

of an aqueous core surrounded by one or more

concentrically arranged bilayer membranes.

• These membranes are commonly composed of

phospholipids or lipid and surfactant.

• Small unilamellar

• Large unilamellar

• Multilamellar vesicles

• Due to their bilayer structure liposomes are able to

accommodate water- and lipid-soluble molecules.

Colloidal dosage Forms - · PDF fileUniversity of Sulaimani School of Pharmacy Dept. of...

Documents

Transcript of Colloidal dosage Forms - · PDF fileUniversity of Sulaimani School of Pharmacy Dept. of...