Multiphase Liquid Dosage Forms: Suspensions

Disperse systems (dispersions)

They are heterogeneous systems – systems containing particulate matters or

globules distributed throughout a medium.

What are the two phases of disperse systems?

dispersed phase (internal phase) and continuous phase (dispersing phase/dispersion medium)

dispersed phase (internal phase)

suspended particles

continuous phase (dispersing phase/dispersion medium)

suspension liquid

Classification of liquid dispersion systems

molecular dispersion, colloidal dispersion, fine dispersion, coarse dispersion

molecular dispersion characteristics

Particles invisible in electron microscope, undergo rapid diffusion

colloidal dispersion characteristics

Particles invisible in ordinary microscope but seen under electron microscope, diffuse very slowly

fine dispersion characteristics

Particles visible under microscope, particles do not diffuse

coarse dispersion characteristics

Particles visible under microscope, particles do not diffuse

molecular dispersion particle size

< 1 nm

colloidal dispersion particle size

1-500 nm

fine dispersion particle size

0.5-10 μm

coarse dispersion particle size

10 -50 μm

molecular dispersion examples

glucose solution, saline

colloidal dispersion examples

milk, fog, paint, colloidal polymer dispersions

fine dispersion examples

magmas and gels

coarse dispersion examples

blood, suspensions and emulsions

tinctures

alcoholic or hydro alcoholic solutions prepared from vegetable materials or chemicals

how much alcohol do tinctures contain?

15-80% alcohol

tinctures differ by ____

methods of preparation (percolation vs maceration)

strength of drug

alcoholic content

mixing tinctures with other solutions may cause

precipitation

what should you protect tinctures from?

high temperature

tinctures should be stored in what kind of container?

light resistant containers

Suspensions

A dispersion of finely divided solid materials suspended in a liquid medium in
which the drug has ____________ solubility.

Oral suspensions have

2.5-10 % (w/v) of solids e.g. antacids, antibiotics

Externally used suspensions have

20% (w/v) of solids. e.g. calamine lotion

Parenteral suspensions

generally used for intra-muscular injections and have 0.5- 30% (w/v) solids. e.g. antibiotics, steroids.

Topical suspensions

used for delivery of drugs to the eye e.g. anti-inflammatory drugs (Nevanac suspension)

Rectal suspension

used for radiologicals and for treating intestinal disorders

Aerosols

formulated as suspensions - solid particles dispersed in a volatile propellant.

DESIRED FEATURES OF SUSPENSIONS

▪ Should settle slowly but re-disperse quickly upon only mild shaking.

▪ Should avoid forming hard cake.

▪ Easy to pour (from bottle), easy to spread (on the skin) or easy to flow (through syringe needle).

▪ Must remain sufficiently uniform for at least the period between shaking the container

and removing the required doses.

▪ Sufficient physical, chemical and microbiologic stability.

▪ Pleasant taste.

Flocculation

Deflocculation

Types of suspensions: flocculated suspensions

Types of suspensions: deflocculated suspensions

Viscosity (η)

The ratio of force applied (shearing stress, F) to the rate of flow (rate of shear, G) of a liquid

What does viscosity influence in suspensions?

physical stability

Classification of flow: newtonian flow

Classification of flow: non-newtonian flow

Classification of flow: non-newtonian pseudoplastic flow

Classification of flow: non-newtonian dilatant flow

thixotropic flow

methods of preparation of suspensions

1) Deflocculated suspension: Using a suspending agent to prepare deflocculated suspensions.
2) Controlled flocculation using flocculating agents
3) Flocculated suspension in a structured vehicle

Deflocculated suspension preparation

Using a suspending agent to prepare deflocculated suspensions

Controlled flocculation preparation

using flocculating agents

Flocculated suspension formulation

in a structured vehicle

THE MAIN STEPS IN THE PREPARATION OF SUSPENSION

.

Wetting

vehicle completely touching solute particles

advantages of suspensions

insoluble drugs disperse evenly

reasonably smaller volume than solutions

greater stability against hydrolysis and oxidation compared to aqueous solutions

masking of disagreeable taste of drug

easier to swallow compared to a solid osage form

depot therapy- for sustained effect

disadvantages of suspensions

difficulty maintaining uniformity and accuracy of doses

sedimentation followed by compaction of particles

loss on storage and transport

usually more difficult manufacturing process compared to simple solid dosage forms

Main issues with suspensions

inadequate dispersion of particles in the vehicle

settling of the dispersed particles

caking of these particles in the sediment that resists re-dispersion

desired features of suspensions

easy to pour, spread, flow

avoids forming hard cake

settles slowly

redisperses quickly upon mild shaking

must remain uniform for at least the period between shaking the container and removing the required doses

sufficient physical, chemical and microbiologic stability

pleasant taste

What route of drug administration does not involve application of pharmaceutical suspensions?

intravenous

Contact angle (θ)

Angle between a liquid and the surface over which it spreads.
▪ Ranges from 0 to 180 degrees

Low contact angle means ______ wetting

high

Wetting is most important for the ____ during the preparation of an insoluble powder in a vehicle

initial dispersion

suspending agents are used to ____ the rate of sedimentation and enhance the appearance of the suspension

increase

the concentration of suspending agents is usually ___ % w/v

0.5-5

The suspending agent should preferably exhibit _____________ flow

types of suspending agents

▪ Natural hydrophilic polymers e.g. tragacanth, xanthum gum, acacia.

▪ Synthetic hydrophilic polymers e.g. methyl cellulose, carboxy methyl cellulose.

▪ Clays e.g. bentonite, veegum.

Why are flocculating agents added?

to reduce and control the particle surface charge to an optimum level

controlled flocculation assures that

particle dispersion for sufficient period of time and prevent formation of a compact sediment that is difficult to redisperse.

flocculating agents

electrolytes, surfactants, polymers

Electrolytes act by ____________ the electrical barrier between the particles.

Important points when choosing flocculating agents

▪ The surface charge of the drug particles
▪ The valency of the electrolyte
▪ Electrolyte concentration

polymers as flocculating agents

high molecular weight compounds, particularly useful for drugs that do not carry a charge

polymers act as flocculating agents by ____ while the remaining parts of the polymer chain project outside

adsorbing onto the surface of particles (or bridging)

Interaction between the polymers and projected polymer chains forms _____________

forms bridges that link the particles into larger aggregates (flocs)

what do polymers mask on drug particles that are charged?

they can mask the charge

Ionic surfactants act as flocculating agents by _________ the charges on the particle
surface e.g. Docusate sodium

Non-ionic surfactants act as flocculating agents by forming a _______________ around
the particles e.g. Tweens or Spans

EVALUATION OF SUSPENSIONS – STOKE'S LAW

• d is the diameter of dispersed particle
• η is the viscosity of the dispersion medium
• g is the gravitational acceleration (m/s2)
• ρs is the mass density of the particles (the dispersed phase) (kg/m3)
• ρo is the mass density of the fluid (the dispersion medium) (kg/m3)

SUSPENSION STABILITY

▪ The suspension should be redispersible on shaking.

▪ A relatively narrow particle size distribution forms a good stable suspension.

▪ Drugs in suspension can undergo polymorphic conversion on storage.

▪ Change in pH of the dispersion medium can cause precipitation.

▪ Drastic changes in temperature can alter the stability of suspensions

PACKAGING AND STORAG

▪ All suspensions should be packaged in wide-mouth containers having adequate
airspace above the liquid to permit thorough mixing by shaking and ease of pouring.
▪ Most suspensions should be stored in tight containers protected from freezing,
excessive heat, and light.
▪ It is important that suspensions be shaken before each use to ensure a uniform
distribution of solid in the vehicle and thereby uniform and proper dosage.

Classify liquid dispersion systems based on their particle size and list their related characteristics.

Describe the rationale for developing suspension dosage forms.

compare flocculation and deflocculation. Are these desirable phenomenon? If yes, why? If no,
why?

Describe classification of flow with examples

List potential disadvantage(s) associated with flocculated suspensions and how it can be
overcome while preparing suspensions?

Describe three main flocculating agents and their mechanism in promoting flocculation.

Why is a wetting agent needed in the preparation of suspension?

Explain the role of various parameters on the rate of sedimentation using Stoke’s law.

Flocculated suspensions

• Particles are in the form of flocs or aggregates

• Weakly bonded

• Rapid sedimentation

• Easily resuspendable

• Resists complete settling

• Less prone to compaction

Deflocculated suspensions

• Particles are in a finely divided state

• Settle slowly

• Closely packed arrangement

• Form hard cake

• Difficult to redisperse if caking occurs

which of the following accurately characterizes colloidal dispersions?

particles diffuse very slowly