Formulation Additives and Isotonicity Modifiers

Formulation Additives

• Buffers enable a solution to resist pH changes when acid or alkali is added.
• Choices for buffers are based on pH, buffering capacity, compatibility, and toxicity.
• Common buffer additives include carbonates, citrates, gluconates, lactates, phosphates, and tartrates.
• Buffers are important in injections, eye drops, and nasal drops, where pH 7.4 is optimal to avoid irritation.
• Buffer selection considers optimal stability, solubility, and bioavailability relative to the physiological pH.

Isotonicity Modifiers

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

Viscosity Enhancement

• Viscosity enhancement additives are used to keep formulations on the skin or in the eyes.
• Povidone, hydroxyethylcellulose (HEC), and carbomer are common gelling agents used in low concentrations.

Preservatives

• Preservation choices depend on adsorption onto the container and efficiency vs. pH.
• Parahydroxybenzoic acid esters are often compared to micelles for preservative effectiveness.

Reducing Agents and Antioxidants

• Reducing agents and antioxidants prevent pharmaceutical product decomposition from oxidation.
• Sodium metabisulphite, BHA, and BHT are common examples.

Sweetening Agents

• Low molecular weight carbohydrates are often used as sweeteners.
• Sucrose is a common sweetener, known for its colorless, soluble, and stable properties over a pH range of 4–8.
• It increases viscosity for a pleasant mouthfeel and masks salty and bitter tastes, soothing the throat (e.g., in cough preparations).
• Sucrose has a cariogenic (tooth decay) disadvantage.

Polyhydric Alcohols

• Polyhydric alcohols like sorbitol, mannitol, and glycerol are used as sweeteners, especially for diabetic patients.

Artificial Sweeteners

• Artificial sweeteners are hundreds or thousands of times sweeter than sucrose and are often used in low concentrations (<0.2%).

Sodium or Calcium Salts of Saccharin

• Sodium or calcium salts of saccharin (E954) are chemically and physically stable over a wide pH range and have high water solubility.

Aspartame

• Aspartame (E951) is an artificial sweetener but may have a bitter or metallic aftertaste, so it is often combined with other sweeteners.

Flavors and Perfumes

• Flavorings and perfumes are often used when the drug has an unpleasant taste (or where a sweetener alone is insufficient) or with pediatric pharmaceuticals.
• Flavors and perfumes can include natural extracts like fruits and aromatic oils or synthetic, cheaper, and more stable variants.
• To mask an undesirable taste, a list of suitable masking flavors can be used.

Colors

• Colors enhance product attractiveness and make them easier to identify.
• Color choices consider color compatibility with flavors.

Liquid Preparations for Cutaneous Application

• Lotions: Designed to be applied without friction, often including humectants and/or alcohol.
• Liniments: Applied by massage into skin and contain counterirritants like methyl salicylate or camphor.
• Paints: Applied in small quantities to the skin or mucosa, using a brush. They contain solvents like alcohol, acetone, or ether and are formulated to leave a film that holds the active ingredients in prolonged contact with the skin.

Ear Preparations

• Ear preparations often use solutions of medicaments in water, glycerol, propylene glycol, or alcohol/water mixtures.
• These preparations can include drops, sprays, or washes.

Eye Preparations

• Eye preparations are sterile, small-volume liquids meant for instillation onto the eyeball or into the conjunctival sac.

Irrigation Solutions

• Sterile, large-volume aqueous solutions for cleansing body cavities and wounds.
• These solutions are typically isotonic.

Nasal Products

• The notes are incomplete for Nasal Products

Oral Liquids

• Elixirs: Clear, sweetened, hydroalcoholic solutions, flavored to enhance palatability. Elixirs can be either non-medicated (vehicle) or medicated (therapeutic).
• Mixtures and Draughts: Aqueous mixtures or solutions/suspensions, often short-term shelf life. Draughts contain higher doses in larger volumes.

Rectal Preparations

• Enemas include aqueous or oily solutions, emulsions, or suspensions for cleansing, diagnostic, or therapeutic purposes.

Intermediate Products

• Aromatic waters and spirits, like peppermint or anise water (carminative) are aqueous solutions of volatile materials that are used mainly for flavoring.
• They are part of the manufacturing process of other preparations and are rarely administered on their own.

Extracts, Infusions, and Tinctures

• Extracts, infusions, and tinctures concentrate the active ingredients from animal or vegetable sources.
• Infusions use 25% alcohol, no heat.
• Extracts are concentrated by evaporation.
• Tinctures are weak alcoholic extracts.

Syrups

• Syrups are concentrated sugar solutions to which medicines and flavorings are added.
• Common examples include codeine phosphate syrup and orange syrup.
• Syrups are designed to prevent bacterial growth due to high sugar content, and lower concentrations are used to reduce osmotic pressure issues in some cases of high sugar solutions.

Manufacture of Solutions

• Solutions are manufactured using different sized mixing vessels with agitation.
• The solute is added to the solvent, with stirring to ensure complete dissolution.
• Heat or size reduction accelerates the process.
• Volatile or heat-sensitive substances are handled carefully to avoid degradation.
• Solutes in very low concentrations (e.g., dyes) are pre-dissolved before mixing with the main solvent quantities.

Stability of Solutions

• Stability of solutions is evaluated for chemical and physical properties.
• Properties considered for evaluation include clarity, color, odor, taste, viscosity, and changes to these after agitation.
• Methods used to evaluate flavor and perfume stability are also noted.