Pharmaceutical Formulation Basics

Formulation Additives

• Buffers enable solutions to resist pH changes when acid or alkali is added.
• Choosing a buffer considers pH, buffering capacity, compatibility, and toxicity.
• Examples of buffering agents include carbonates, citrates, gluconates, lactates, phosphates, and tartrates.
• Buffers are crucial in injections, eye drops, and nasal drops to maintain a pH of 7.4 and avoid irritation.
• Optimal stability, solubility, and bioavailability are linked to the physiological pH.

Isotonicity Modifiers

• Isotonicity modifiers are added to injections and large-volume ophthalmic solutions to prevent pain, irritation, and damage to mucous membranes.
• These modifiers are added after other ingredients.
• Dextrose and sodium chloride are commonly used isotonicity modifiers.

Viscosity Enhancement

• Viscosity enhancers help liquids remain on the skin or in the eyes.
• These include low concentrations of gelling agents like povidone, hydroxyethylcellulose (HEC), and carbomer.

Preservatives

• Preservatives can be chosen based on their adsorption onto the container and efficiency compared to pH.
• Parahydroxybenzoic acid esters or micelles are examples of preservatives.

Reducing Agents and Antioxidants

• Reducing agents and antioxidants prevent pharmaceutical product decomposition through oxidation.
• Examples include sodium metabisulphite, BHA, and BHT.

Sweetening Agents

• Low molecular weight carbohydrates are used as sweeteners.
• Sucrose is colorless, soluble, and stable over a pH range of 4-8.
• Sucrose increases viscosity resulting in a pleasant mouthfeel and masks salty or bitter tastes.
• Sucrose can soothe throat membranes, especially in antitussive preparations.
• A disadvantage of sucrose is its cariogenic property.
• Other polyhydric alcohols, such as sorbitol, mannitol, and glycerol, serve as sweeteners, particularly for those with diabetes.
• Artificial sweeteners such as sodium or calcium salts of saccharin (E954) are highly soluble in water and chemically and physically stable.
• Aspartame (E951) is another artificial sweetener but has a bitter or metallic aftertaste. It is often combined with sugars.

Flavors and Perfumes

• Flavors and perfumes are used when a product has an unpleasant taste.
• They enhance palatability, particularly in pediatric products and liquid products.
• Natural sources include fruit juices, aromatic oils (e.g., peppermint, lemon), and herbs/spices.
• Synthetic flavors are often cheaper, more readily available, and more stable. They are commonly used in solutions (aq/alc) and powders.
• Suitable masking flavors for various tastes are also listed.

Colors

• Colors enhance the attractiveness of products, compatible with flavor.
• Colors improve product identification.

Liquid Preparations for Cutaneous Application

• Lotions: Applied to skin without friction. Often contain humectants or alcohol.
• Liniments: Massaged into skin. Often contain counterirritants (e.g., methyl salicylate or camphor).
• Paints: Applied to skin or mucous membranes in small amounts (e.g., small brushes). Solvent evaporates, leaving a film with the active agent. Viscosity modifiers ensure prolonged skin contact.

Ear Preparations

• Ear preparations are also known as otic or aural products.
• They are simple solutions of drugs in a suitable vehicle for local use.
• Vehicles include water, glycerol, propylene glycol or alcohol/water mixtures.
• Applications include drops, sprays, or washes.
• Ear preparations are used for antibiotics, antiseptics, cleansing solutions, and wax softeners.

Eye Preparations

• Eye preparations are small-volume sterile liquids.
• They are applied to the eyeball or conjunctival sac to achieve a local effect.

Irrigation Solutions

• Irrigation solutions are large-volume aqueous-based solutions for cleaning body cavities and wounds.
• These solutions must be isotonic.

Nasal Products

• Nasal products are not further detailed.

Oral Liquids (Elixirs)

• Elixirs are clear, sweetened, hydroalcoholic solutions for oral use, often flavored for palatability.
• Types include non-medicated (vehicles) and medicated (therapeutic effect).

Oral Liquids (Mixtures and Draughts)

• Mixtures are aqueous preparations, either solutions or suspensions, with a short shelf-life.
• Draughts are mixtures with one or two large doses (around 50 mL).

Rectal Preparations (Enemas)

• Enemas are aqueous or oily solutions, emulsions, or suspensions administered rectally.
• Enemas are used for cleansing, diagnostic, or therapeutic purposes.

Intermediate Products (Aromatic Waters and Spirits)

• These are aqueous solutions of volatile materials.
• Primarily used for flavoring.
• Not often administered directly. Examples include peppermint and anise water.
• Concentration is usually 1:40.

Extarcts, Infusions, and Tinctures

• Extracts, infusions, and tinctures are concentrated solutions of active principles from plants or animals.
• Infusions are made without heat and use 25% alcohol.
• Extracts are concentrated using evaporation.
• Tinctures are weak alcoholic extracts.

Syrups

• Syrups are concentrated solutions of sucrose or other sugars.
• Medicaments and flavorings are often added to them.
• Examples include Codeine Phosphate Syrup and Orange Syrup.
• Syrups resist bacterial growth due to high sugar content (85%), working through osmosis.
• Lower sugar concentrations may use polyhydric alcohols (sorbitol, glycerol, propylene glycol) as these create osmotic pressure.
• Problems can include crystallization of sugar, so polyhydric alcohols or invert syrup are used as alternatives.

Manufacture of Solutions

• Solutions are made on small or large scales using mixing vessels with agitation.
• Solutes are added to solvents for complete dissolution, potentially using heat or size reduction for faster mixing.
• Easily volatile or heat-sensitive materials are handled with careful cooling and to prevent adsorption issues.
• Solutes in low concentrations can be predissolved.

Stability of Solutions

• Chemical and physical factors affect solution stability.
• Clarity, color, odor, taste, and viscosity of the solution should be assessed.
• Clarity can be checked visually or by optical density after stirring.
• Color is assessed visually and spectrophotometrically.
• Flavors and fragrances should be checked using chromatographic methods.