Pharmaceutical Solutions: Types and Solubility

• Solution: homogeneous mixture with solute dissolved in a solvent.
• Solvent: liquid (pure or mixture) in a solution.

Pharmaceutical Solutions

• Pharmaceutical solutions: liquid with dissolved chemical substances (solutes) in a miscible solvent.
• Solubility: physical property.
• Measurement: maximum solute dissolved in solvent at equilibrium.

Types of Solutions:

• Very soluble: less than 1 part of solvent needed per part of solute.
• Freely soluble: 1 to 10 parts of solvent needed.
• Soluble: 10 to 30 parts of solvent needed.
• Sparingly soluble: 30 to 100 parts of solvent needed.
• Slightly soluble: 100 to 1,000 parts of solvent needed.
• Very slightly soluble: 1,000 to 10,000 parts of solvent needed.
• Practically insoluble: more than 10,000 parts of solvent needed.

Administration:

• Orally: mixtures, elixirs, linctuses, draughts, syrups, pediatric drops.
• Mouth/Throat: mouth washes, gargles, throat paints, sprays.
• Body Cavities: douches, enemas, ear drops, nasal sprays.
• Body Surfaces: collodions, liniments, lotions, paints.

Advantages:

• Easier for children/adults to swallow compared to tablets/capsules.
• Absorption is immediate, no dissolving needed.
• Uniform dosage is ensured.
• Safe administration of substances like potassium iodide and bromide.
• Attractive appearance psychologically beneficial.

Disadvantages:

• Less stable than solid forms because deleterious changes happen faster.
• Masking unpleasant flavors is hard.
• Bulky to carry.
• Needs a spoon.
• Breakage equals total messy loss.

Solvents:

• Selection based on: solubility, clarity, toxicity, viscosity, compatibility, inertness, palatability, odor, color, and economy.
• Water is often preferred because it meets most criteria.

Types of Water:

• Water is a major ingredient, used as vehicle and solvent.
• Ideal due to being tasteless, non-irritating and lacking pharmacological activity.
• Six USP recognized types of water for dosage forms.
• Purified Water: obtained by distillation, ion exchange, or reverse osmosis, ≤10 ppm total solids, pH 5-7.
• Used in prescriptions/manufactured products except parenteral and ophthalmic.
• Water for Injection: meets purified water standards and is pyrogen-free.
• Used a lot as a solvent for parenteral solutions.
• Sterile Water for Injection: sterile water for injection packaged in single-dose Type I/II glass, which is then sterilized.
• Bacteriostatic Water for Injection: sterile water for injection with added bacteriostatic agents.
• Sterile Water for Inhalation: purified by distillation/reverse osmosis, then sterilized.
• Lacks antimicrobial agents.
• Should not be used parenterally or for other sterile dosages.
• Sterile Water for Irrigation: sterile water for injection, suitably packaged.

Alcohol as a Solvent:

• Second most common solvent for organic compounds.
• Hydroalcoholic mixtures can dissolve alcohol and water-soluble substances.
• Widely used, miscible with water, dissolves many water-insoluble ingredients.
• Antimicrobial preservative activity.

FDA Alcohol Recommendations:

• OTC oral products for children under 6: limit 0.5%.
• Products for children 6-12: 5%.
• Children above 12/adults: 10%.

Types of Solutions

• Glycerin: used as solvent, sweetener, antimicrobial preservative, viscosity enhancer.
• Propylene Glycol: solvent, extractant, preservative in pharmaceutical formulations, including parenterals.
• Can be used as antiseptic.

Preparation of Solutions & Considerations:

• Purpose of drug, internal/external use, solubility/concentration, liquid vehicle selection, physical/chemical stability are all considerations for preparations.
• Oral preparations: color, odor, and taste.

Three Main Categories for Solution Preparation:

• Simple solutions
• Chemical reaction
• Extraction

Solution Types:

• Simple solutions: dissolve solute in most of solvent, mix, and add solvent to the proper volume.
• Solution by chemical reaction: react two or more solutes together in solvent.
• Solution by extraction: extract drugs with water or water with added substances.

Factors Affecting Dissolution:

• Solute-solute interactions
• Solvent-solvent interactions
• Solvent-solute interactions.

Steps in Making a Solution:

• Breaking up solute into individual components (expanding the solute).
• Overcoming intermolecular forces in the solvent to provide room for the solute (expanding the solvent).
• Allowing the solvent and solute to interact and form the solution.

Syrups

• Concentrated, viscous, aqueous solutions of sugar/sugar substitute with or without flavors and medicines.
• Simple syrup: purified water used, 85% sucrose.
• Also used to coat tablets (for masking disagreeable aromas or acrid taste).
• Alcohol often included as preservative and solvent for flavors.
• Medicated syrup: aqueous with medicinal substance added.
• Flavored syrups: typically not medicated, contain aromatic/flavored substances.

Syrup Preparation Techniques:

• Solution with Heat: only if constituents will not degrade.
• Agitation without Heat: for heat sensitive volatile substances.
• Addition of sucrose to liquid medication.
• Percolation method.

Solution with Heat:

• Heats purified water to 80-85°C, then removes from heat.
• Add sucrose with agitation.
• Add heat-stable components when hot.
• Cool the mixture.
• Then, it is brought to volume and the purified water is added.

Agitation Without Heat:

• For heat sensitive volatile substances
• A vessel needs to be larger than the final volume
• Intense agitation needed with slow addition of purified water to avoid sucrose spillage.

Sucrose Addition to Liquid Medication:

• Fluid extracts (tinctures) used
• This syrup method can develop precipitates.
• Alcohol leads to precipitation because it solubilizes the resinous and oily substances when you add the water.

Percolation Method:

• Purified water or medicinal component passed through crystalline sucrose, forming syrup, thus dissolving crystal.
• Preparation of drug extractive.
• Preparation of the syrup.

Percolation Best Practices

• You should use a cylindrical or semi-cylindrical and cone percolator.
• A coarse granular sugar must be used so liquid can permeate, otherwise it results in a compact mass.

Other Solution Considerations

• In dilute solutions, sucrose creates nutrients for microorganisms.
• Solutions with ≥65% sucrose inhibit microorganism growth.
• Saturated solutions cause sucrose crystallization when there are changing temperatures.
• Polyols (glycerin or sorbitol) may be added to inhibit sucrose crystallization.

Artificial Syrups:

• Suitable for people who need to regulate sugar/calorie intake.
• They do not cause an increase in blood sugar levels.
• Formulas included glycerin, but glycerin/proplyene glycol turns into glucose within the body.

Non-Aqueous Solutions:

• There are four groups: Alcoholic solutions, Etheral solutions, Glycerin solutions, Oleaginous solutions.
• Alcoholic or hydroalcoholic solutions (elixirs & spirits).
• Etheral solutions contain collodions.
• Glycerin solutions contain glycerites.
• Oleaginous solutions contain liniments, medicated oils, oleo-vitamins, sprays, and toothache drops

Elixirs

• Clear, flavored, sweetened hydro-alcoholic liquids for oral use.
• The main ingredients are alcohol and water.
• Solvents used to increase drug solubility.
• More fluid than syrups.
• Can be used as flavors and vehicles.

Elixirs Examples:

• Aromatic Elixir USP for drug substances
• Medicated elixirs: Dexamethasone Elixir USP and Phenobarbital Elixir USP.
• Alcohol Concentrations: 5-40%.

Elixirs & Mixing

• Elixir MAY contain water and alcohol soluble ingredients.
• High alcohol concentration may precipitate aqueous soluble substances.
• High water concentration may precipitate alcohol soluble substances.
• 5 ml dose needs diluting.
• The diluent is syrup (except for codeine linctus, use chloroform).
• Fresh dilutions required, two-week supply maximum (unless specified).

Linctuses:

• Used for coughs.
• Sedatives and expectorants used as ingredients.
• Syrup vehicle soothes sore throats.
• Undiluted, sipped slowly (to obtain local action).

Spirits:

• Alcoholic or hydroalcoholic volatile solutions.
• Active ingredients can be solids, liquids, or gases like the aromatic waters..
• High in alcohol (over 60%).
• May contain higher aromatic/volatile substance concentrations.
• When mixing with water/aqueous preps, volatile substances form milky preps.
• Salts can precipitate with spirits due to solubility differences.
• Store spirts must be tight and light-resistant, keep in a cool place.
• Spirits used pharmaceutically as flavoring or medicinally. Used orally, externally, or by inhalation (reduces pungency).

Liniments

• Liquid preparations for external use.
• Can be alcoholic solutions, oily solutions, or emulsions.
• Two vehicle types: high alcohol concentration or oil.
• While alcohol acts as a solvent, it helps penetration, potentiates counter-irritation.
• Oils such as bland oil are less irritating than alcohol and spreads more easily.
• Mild counter-irritants (soap liniment) treat sprains and bruises and have soap.

Liniments: Cautions

• Do not apply to broken skin, especially if with alcohol solvent.
• Label with "Not to be applied to wounds or broken skin" and "For external use only".
• Label 'Inflammable' for alcoholic solvent ones.
• Store cool; Liniments have volatile ingredients.

Lotions

• Soothing preparations applied gently, differing from stimulating liniments.
• Half the official lotions are solutions.
• Ingredients: simple salts (copper and zinc), lead subacetate, soluble in water or salicylic acid in alcohol.
• Lead lotions are empirical treatments for sprains/bruises.
• Useful for skin conditions.
• Some lotions (e.g., evaporating lead lotion) contain alcohol for cooling.
• High alcohol concentrations defatting countered by castor oil.

Fresh Considerations for Lead Lotions:

• Lead lotions usually contain freshly boiled and cooled water because the dissolved carbon dioxide precipitates the lead carbonate.
• Salicylic Acid lotion and Salicylic Acid and Mercuric Chloride Lotion use alcohol and acetone respectively must be labeled as their flammability is high.
• Lotions must be labeled 'For external use only'.

Paints

• All official paints are solutions.
• The solvent for crystal violet paint is water; some organic solvents are used for other paints.
• Spillage must be prevented when dispensing these type of solutions, as the dye can get everywhere.
• Dyes can still be light and float into the air- must be careful.
• Skin paints contain solvents- dry and resinous feeling.
• Throat are viscous, contain glycerol, prolong medication to the throat.
• All, except throat paints, should be labeled "For external use only."
• Everything (except magenta paints) should be labeled for flammability.
• Podophyllum Paints should carry a warning.

Collodions

• Liquid preparations containing pyroxylin in ether/ethanol.
• With the use of a brush the liquid is spread out. Once the solvent is evaporated there will be a film on the skin.
• There are two kinds.

Collodions Storage and Labels:

• Small light-resistant containers.
• Stored in a cool place.
• Marked as flammable.
• Not near flames.

Parenteral Solutions

• Sterile pyrogen-free preparations.
• Injected into the body.
• Require purity/sterility.
• Require preparation and administration via using asceptic techniques.

Types of Preparations for Injections:

• Liquid preparations which can be substances or solutions thereof
• Dry solids that become solutions with added vehicles.
• Liquid preparations where a drug is dissolved or dispersed in an emulsion.
• Liquid preparation of a solid suspended in a liquid.
• Dry soilds which become suspended with additional vehicles.

Miscellaneous Solutions:

• Draughts
• Douches
• Gargles
• Enemas
• Mouth Washes
• Ear Drops
• Throat Paints
• Nasal Drops
• Throat and Nasal Sprays