Emulsions, Oral Solutions, and Suspension

Emulsions

contains at least two immiscible liquid phases that consist in most cases of water and oil

Water-in-oil emulsions

water droplets are dispersed throughout a continuous oil phase

What is the dispersed (internal) phase of an oil-in-water (O/W) emulsion?

Oil droplets

Which description fits an O/W emulsion compared with a W/O emulsion?

Creamy and white, easily water washable

W/O emulsions are more glassy and translucent, oilier, and harder to wash off.

Why are emulsions thermodynamically unstable?

Reducing particle size increases surface area and surface energy, so droplets try to merge

Making small droplets creates a large surface area with high surface energy. Droplets attempt to come together to reduce that area. Repulsive (high) zeta potential helps keep them apart.

Which of these is NOT one of the four routes of emulsion failure shown in the lecture?

Micellization

he four routes are breaking, coalescence, creaming, and flocculation. Micelle formation happens above the CMC and is not an emulsion failure.

What determines whether an emulsion ends up O/W or W/O?

The emulsifying agent: more lipid soluble gives W/O, more water soluble gives O/W

The emulsifier controls which phase ends up external.

Which emulsifier class is the most commonly used, and can make both O/W and W/O emulsions?

Wetting/surface active agents (Spans, Tweens, SLS)

Surfactants contain both hydrophilic and lipophilic groups and are the most commonly used. Hydrophilic colloids and proteins make O/W only, and high MW alcohols are thickeners and stabilizers for O/W.

Which surfactant class is the default for parenteral and ophthalmic use, being the least irritant?

Nonionic

Nonionic surfactants (polysorbates/Tweens, sorbitan esters/Spans) are insensitive to pH and salt and are by far the least irritant. Cationics like benzalkonium chloride are more irritant.

What happens to surfactant above the critical micelle concentration (CMC)?

The interface is saturated, so extra surfactant forms micelles that can solubilize hydrophobic drugs

solubility rises with surfactant concentration.

HLB ranges: which range produces W/O emulsions and which produces O/W?

W/O: 3-6; lipophilic

O/W: 8-18 hydrophilic

A blend is 40% Span 60 (HLB 4.7) and 60% Tween 60 (HLB 14.9). What is the blend's HLB?

10.8

Weight each HLB by its fraction: (4.7 × 0.40) + (14.9 × 0.60) = 1.9 + 8.9 = 10.8.

How can emulsifier lower interfacial tension and help prevent droplets from coalescing?

Emulsifier are amphiphiles: polar head (hydrophillic) and lipid-loving tail creates a film layer

Stops droplet merging again: The film stays at the droplet surface as a barrier.

What causes flocculate?

Low zeta potential, lets droplets cluster → coalescene

How to use HLB to prepare an emulsion?

Select emulsifying agents having the same or nearly the same HLB number as the required HLB of the oil phase of the emulsion

What should the HLB be for W/O emulsion?

5

What should the HLB be for O/W emulsion?

12

Why ophthalmic preparations must be sterile?

Ocualar infections can cause ocular ulcerations and sometimes loss of sight

Bacterial (Staph)

Fungal (Fusarium, Aspergillus, Candida)

Parasitic (Acanthamoeba)

How to avoid contamination in ophthalmic solutions?

Contamination occurs if dropper is touched on table, face or eylid

With a Drop-Tainer type container, tip cannot touch eyelid, or finger when lid is replaced

All multi-dose ophthalmic solution containers must contain an antimicrobal preservative

Quaternary Ammonium Compounds

type of ophthalmic preservative

cationic+ surfactants, they sting

prevents bacterial growth

most commonly used preservative

good stability and antimicrobial

TOXIC EFFECT: altering corneal permeability

CON: break superficial lipid layer of tear film into tiny droplets

not a good preservative for artifical tear preparations

taken up into contact lenses can result in toxicity

Chlorhexidine

type of ophthalmic preservative

similar to BAK in microbial activity, but does NOT alter corneal permeability → not toxic to eye

Chlorobutanol Advantages

type of ophthalmic preservative

Effective against most bacteria and fungi

compatible with most ingredients

• Rapid hydrolysis to HCl with high temperature in unbuffered solutions

• Ophthalmic solutions containing chlorobutanol should be buffered at a pH of 5-5.5

  • to prevent formation of HCl

Aromatic Alcohol: Benzyl alcohol and Phenylethyl alcohol

type of ophthalmic preservative

similar to chlorobutanol (alcohol binds to the cell membrane of bacteria)

does not convert to HCl

combinations of chlorobutanol and phenylethyl alcohol have been reported to be more effectives against P. aeruginosa, Staphylococcus aureus, Proteus vulgaris than each preservative used alone.

What are ophthalmic vehicles?

enhance drug action by increasing viscosity → Retention time increases

high molecular weight polymers

some can even bind to the corneal surface to increase drug retention

What are the five commonly used vehicles?

Povidone
Polyvinyl alcohol (PVA)

Hydroxypropyl methylcellulose
Poloxamer-407
Ointments

Polyvinyl alcohol (PVA)

type of ophthalmic vehicle

most comfortable, non-irritating to eye, may facilitate healing of an abraded cornea

water soluble, most products contain 1.4%

Hydroxypropyl Methylcellulose (HPMC)

type of ophthalmic vehicle

similar to PVA, non irritating

0.5%

exhibits TWICE the ocular retention of a 1.4% solution of PVA

Povidone

type of ophthalmic vehicle

not bound to membrane surfaces

Does not provide long-lasting viscosity enhancement

Viscosity does not change unles pH of solution reaches 1.0

overall, NOT A GOOD AGENT TO USE

Poloxamer-407

type of ophthalmic vehicle AND surfactant (has hydrophillic and lipidphillic group)

First polyionic compound to be evaluated for use in the eye

produces artificial microenvironment in the tear film that enhances bioavailability of certain drugs

Ointments (eye)

type of ophthalmic vehicle

PRIMARY purpose is to increase ocular contact time

Combinations of petrolatum and mineral oil (60%/ 40%)

Usually semi-solid at room temperature

Contact time is 2-4 times longer when compared to an aqueous solution

Usually well tolerated by patient with no stinging or irritation

At what pH should a drug be for the eye?

7.4

should not sting

however this is hard to achieve because most drugs are stable at acid pH

adjustment is a compromise between stability and comfort of the patient

What is the ideal tonicity of eye drops?

isotonic 0.9% + 0.2% sodium chloride

Eye can tolerate tonicity of between 0.6% and 1.8% NaCl

What are the key steps of eye drop administration that patients USUALLY SKIP?

10. Use a finger to put gentle pressure over the opening of the tear duct

12. If multiple drop therapy is indicated, wait at least 5 minutes before instilling the next drop. This pause helps to ensure that the first drop is not flushed away by the second drop, or that second drop is not diluted by the first.

Why is so little of an eye drop absorbed (about 1%)?

drop (~50 µL) far exceeds what the eye holds (~10 µL), and most drug is flushed away in 1-2 minutes

Normal tear volume is about 7 µL and the eye can hold about 10 µL, but commercial drops average 50 µL. The excess drains via the nasolacrimal duct. The ideal volume would be about 5 µL.

A patient uses both eye drops and eye ointment. What is the correct order and timing?

Drops first, then ointment at least 10 minutes later

Instill drops at least 10 minutes before the ointment so the ointment does not act as a barrier to drug penetration. For multiple different drops, wait at least 5 minutes between them. Counsel that ointment may temporarily blur vision.

Solutions

liquid preparations containing one or more drug substances molecularly dispersed in a suitable solvent or a mixture of mutually miscible solvents

All ingredients (solute) in a solution must be ______ in the dissolving vehicle solvent.

completely soluble

What is the most common co-solvent and why is it needed?

alcohol, because it helps hydrophobic solutes dissolve better

Solubility

quantity of a drug that can be maintained in solution in given solvent under specific conditions

Must completely dissolve medications and any other sold ingredients

Solute generally the smaller amount being dissolved, solvent is the larger liquid component

1g/mL

For a practically insoluble or insoluble solution, what would be the parts of solvent required for 1 part of solute and the solubility value by USP standards?

10,000 or greater parts of SOLVENT for 1g of solute
or <0.1 mg/mL

Saturated solution

contains the maximum amount of solute that the solvent can accommodate at room temperature and pressure

Supersaturated solution

contain a higher amount of solute than the solvent can normally accommodate at room temperature and pressure