Lecture 3: solution dose form

What is a pharmaceutical solution?

A thermodynamically stable, one-phase system where one or more solutes are completely dissolved in a solvent, forming a homogeneous mixture

What can solutes in solutions include besides drugs?

Flavoring agents, coloring agents, preservatives, stabilizers, and buffering salts

What are requirements for an appropriate solvent?

Must dissolve all components at desired concentration, be non-toxic, safe, and aesthetically acceptable

Advantages of solutions as dosage forms?

Homogeneous, immediate absorption, flexible dosing, usable by many routes, and suitable for patients who cannot swallow solids

Disadvantages of solutions as dosage forms?

Less stable, solubility limitations, taste issues, bulky packaging/transport, and require patient measurement (less accurate than tablets/capsules)

How are solutions prepared to avoid precipitation?

Dissolve solutes in their most soluble solvent first, then add others with stirring

What factors increase dissolution rate?

Heating (if stable), reducing particle size, and stirring

What does the Noyes-Whitney equation describe?

The rate of dissolution, affected by diffusion coefficient, surface area, concentration gradient, and diffusion layer thickness

What is pharmaceutical elegance in solutions?

Clarity, absence of particulates, and confidence in product quality. Solutions may be filtered to remove particulates but not to remove undissolved solute

Define solubility.

The maximum concentration of a solute that can dissolve in a solvent at a given temperature

What affects rate vs extent of solubility?

Particle size and agitation affect rate only; temperature and pH affect actual solubility

What principle explains “like dissolves like”?

Solutions form when solvent-solute interactions balance or exceed solute-solute and solvent-solvent forces

How does temperature affect solubility?

If dissolution is endothermic, ↑ temp ↑ solubility; if exothermic, ↑ temp ↓ solubility

What is the significance of partial molar volumes?

Solution volumes are not additive; qs ad ensures correct final volume despite displacement effects

What is displacement volume in reconstitution?

Volume occupied by drug powder after adding diluent (important for antibiotics like amoxicillin)

How does pH affect solubility of weak acids/bases?

Weak bases form salts with acids (↑ solubility), weak acids form salts with bases (↑ solubility). Henderson-Hasselbalch equation applies

Properties of Purified Water USP?

No additives, ≤0.001% solids, obtained by distillation, ion-exchange, or reverse osmosis

Restrictions for Alcohol USP (ethanol) in oral solutions?

<0.5% under 6 yrs, 5% for 6–12 yrs, 10% for >12 yrs

Why is methanol or ethylene glycol never used pharmaceutically?

Both are toxic

Uses of propylene glycol & glycerin in solutions?

Solvents, co-solvents, humectants, and mild preservatives

Common routes of solution administration?

Oral, ophthalmic/otic/parenteral, topical

What auxiliary label is required for topical solutions?

“For external use”

What are elixirs?

Clear hydro-alcoholic oral solutions (up to 30% alcohol), flavored/sweetened, stored tightly sealed

What are tinctures?

Hydro-alcoholic solutions (15–80% alcohol), for oral or topical use, often precipitate on dilution, declining in use

What are aromatic waters?

Aqueous solutions saturated with volatile oils for flavor/odor

Examples: Dill, peppermint, orange, rose water

What is collodion?

What solvents are used in collodions?

What are collodions used for?

What happens when collodion is painted on the skin?

Liquid preparations containing pyroxylin

Usually alcohol and diethyl ether

Delivery of keratolytic medications

It dries to form a flexible nitrocellulose film

What are syrups?

Concentrated aqueous sugar/sugar substitute solutions, often flavored, used as vehicles into which medications may be added

Examples: cherry, orange, cocoa syrup

Commercial sugar-free product is Ora-sweet

How much sucrose is in Simple Syrup NF?

85% sucrose

May also be sugar-free containing: propylene glycol, glycerin, sorbitol (excluding sucrose)

How are syrups preserved?

High sucrose (self-preserving), or preservatives (alcohol, benzoates, parabens, potassium sorbate) if diluted

Can you filter a solution to remove undissolved solute?

No. Filter only to remove particulates; never to remove undissolved solute. Aim for a very clear solution (pharmaceutical elegance)

Three ways to increase dissolution rate?

Heating (if solvent non-volatile and solute heat-stable)

reduce particle size

stirring.

Do particle size and agitation change solubility?

They change rate, not extent of solubility; temperature and pH can change solubility.

Why “qs ad” instead of pre-measuring water?

Solution volumes are not additive (e.g., water + ethanol); “qs ad” ensures correct final volume despite displacement.

What is displacement volume and why does it matter?

Volume occupied by drug powder after diluent is added; affects final concentration

DV varies by drug/strength/brand

Why can a hydro-alcoholic vehicle prevent precipitation?

Raising pH of morphine sulfate forms free base (poorly water-soluble), but alcohol dissolves free base, maintaining clarity.

What lowers water solubility in organics?

Adding halogens (↑MW without ↑polarity). More polar groups ↑ water solubility.

Other forms of syrups

May also be sugar-free containing
propylene glycol, glycerin, sorbitol replacing
sucrose

Commercial sugar free vehicle – OraSweet-S

Components of product label

• name of product and dosage form

• Strength of product

• Quantity

• Direction of use

• Expiring dates

• Auxiliary labels

• Preservative content

Preparations of syrups

Heat if no volatile or heat-liable

May also use stirring without heat

Percolation