Oral & topical solutions

Oral & topical solutions

Pharmaceutics Shenandoah University BJD School of Pharmacy

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Lecture Objectives:

• Understand the proper definition and USP nomenclature for solutions
• List advantages and disadvantages of solutions as a dosage form
• Recognize components of oral and topical solutions
• Describe components of solubility (solvents and solutes) and the role they play in solutions
• Identify signs of instability for solutions
• Understand the use of preservatives in solutions
• Identify packaging, storage, and beyond use dates (BUD) for compounded solutions

Types of Solutions

• Aqueous: water is used as the solvent (most common)
• Examples: syrups, saline solutions, enemas, nasal sprays
• Non Aqueous: contain alcohols or oils as the solvent (no water or very small amount of water)
• Examples: oleaginous solutions, collodions, liniments
• Hydroalcoholic: solvent is a combination of water and alcohol
• Examples: elixers and tinctures

USP Definition

• Solutions are liquid preparations containing one or more drug substance dissolved in a suitable solvent or mixture of mutually miscibile solvents.
• Solutions can be administered via inhalation, introcular, intravesicle, oral, nasal, ophthalmic, otic, parenteral, rectal and topically.
• USP Nomenclature for Solutions: {drug} for {route of administration} solution
• Examples: Amoxicillin for oral solution
• Floxetine oral solution
• Clotrimazole topical solution
• Ipratropium Bromide inhalation solution

Miscibile: when two liquids can combine in any ratio to form a homogeneous mixture (solution)

If a solution has "for" in the name, this indicates that it is in a powder form and needs to be mixed to form the solution.

Visual content is a cross-cutting, universal language, like music. We are capable of understanding images from millions of years ago, even from other cultures.

Solutions as a Dosadge Form

Drugs are less stable in solution than dry form Some drugs not souble in acceptable solvents Can be difficult to mask taste Difficult to handle, package, transport and store Require measurement by patient or caregiver Require counseling on the use of liquid medications

DISADVANTAGES

Homogeous doses Immediately available for absorption Can be used for most route of administration Good for patient's who cannot swallow tabs/caps Easily adjust dose Ingredients for other dosage forms

Advantages

Components of oral solutions

• Solvents
• Indicated for internal use: water, glycerin, alcohol, propylene glycol
• NOT indicated for internal use: aromatic hydrocarbons, methyl alcohol, volatile ethers, ketons, low molecular weight esters
• Excipients
• Sweetners (sugars, polyols, non-nutritive), antioxidants, buffers, colorants, flavors, preservatives, viscosity enhancing agents

Solubility

• Solubility: maximum concentration of a solute that may be completely dissolved in a solvent at a specific temperature and pressure
• Miscibility: when two liquids can combine in any ratio to form a homogeneous mixture (equivalent of soluble but for liquids
• Solute: a substance (drug) that is dissolved into a solvent to form a homogenous solution (either electrolytes or non-electrolytes)
• Electrolytes: will dissociate (ionize) into solvents
• Strong electrolytes: sodium chloride, magnesium sulfate
• Weak electrolytes: most drugs
• Non-electrolytes: will not dissociate into solvents
• Examples: dextrose, sucrose, glycerin, ethanol, chloroform, urea
• Solvent: a susbtance (usually liquid) that dissolves other substances (drugs-solutes) without changing their molecular strucuture to form a homogeneous solution (either polar, non-polar, or semi-polar)
• Polar: water (dissolves better in polar)
• Non-polar: mineral oil (dissolves better in non-polar)
• Semi-polar: acetone, propylene glycol (dissolves better in semi-polar)

Remember: "like dissolves like" when it comes to solvent solubility!

process of solubility

1. Solvent molecules are separated to provide space for the solute
2. Interionic or intermolecular bonds of the solute are broken
3. Interaction occurs between the solvent and the solute molecule or ion

WEak Electrolytes

Most drugs are weak electrolytes. Weak electrolytes can be further classified as weak acids and weak bases.

• Weak Acids: salt forms of chemicals that are weak acids include sodium, potassium, and calcium
• Examples: sodium phenytoin, sodium carbonate, sodium phenobarbital
• Weak Bases: salt forms of chemicals that are weak bases include sulfate, hydrochloride, tartate
• Examples: sulfate tetracaine, hydrochloride, metoprolol tartrate

factors that affect solubility of drugs

• Characteristics of solute/solvent
• Temperature
• Presence of multiple/other solutes
• Solvent systems (cosolvents)
• Solvent pH

Characteristics of solutes that increase water solubility

• Increased number of polar groups (OH, NH2, COOH) in the solute
• Solubility is decreased with more carbon atoms in the solute
• Lower melting point increases solubility for organic molecules
• Anhydrous solutes are more soluble than hydrated forms
• Salt form is usually more soluble than the free form of the drug

Optimized Temperature increases solubility

• Some compounds have greater solubility at higher temperatures (this is not true for all compounds, as some may be soluble at lower temperatures)
• Selection of appropriate temperature from storage and preparation of the solute ensures the solutions holds the appropriate amount of drug
• Selection of appropriate temperature also improves solubility and increases rate of solution formation (speed that the drug dissolves)

Effect of Multiple Solutes on SOlubility

Aqueous solubility of nonelectrolytes is usually affected by the addition of an electrolyte.

• Salting Out: precipitation of organic solutes when electrolytes (or salt) is added
• Salting In: increase in solubility of an organic solute when electrolyte is added
• This is a rare occurrance
• Complexation: insoluble solute reacts with a soluble substance to form a soluble complex (together they are soluble

Solvent systems affect on solubility

Solubility of a drug is correlated to the polarity of the solvent. Altering this relationship can change drug solubility for optimal polarity.

1. Change the polarity of the solvent system by mixing solvents of varying polarities (cosolvents) to form a system of optimal polarity for the drug that needs to be put into solution
2. Change the polarity of the solute by shifting between its undissociated and ionic (dissociated) states by alterning the pH of the system

Visual content is a cross-cutting, universal language, like music. We are capable of understanding images from millions of years ago, even from other cultures.

SOLVENT PH AFFECT ON DRUG SOLUBILITY

pH

Solubility is lower at lower pH

Solubility is higher at higher pH

WEAK ACID

WEAK BASE

Small changes in pH can significantly affect solubility and stability of a drug in solution.

• Dissociated form of a drug is more soluble than the undissociated form
• pH at which a drug will precipitate can be predicted using the Henderson-Hassselbach Equation

Contamination of solutions

Microbial bacterial, mold, and yeast can proliferate and grow in solutions.

Solution formulations are most stable between pH 3 and 9. This happens to also be the pH range that supports most microorganism proliferation. Therefore, preservatives need to be added to solutions to prevent such growth.

Signs of instability in a solution

• Precipitation
• Change in appearance or smell
• Discoloration, tubidity, or gas formation can indicate microbial contamination in oral solutions without preservatives

Descriptions of signs of instability for all dosage forms are outlined in USP <1191>.

Solution preservatives

• Antimicrobial preservatives can be microcidal, microstatic, and sporicidal
• Need to consider if the preservative is soluble at the necessary concentration and if the undissociated form of the preservative can endter the microorganism and be effective in preventing growth
• Preservative examples for oral solutions: parabens, benzoic acid, sodium benzoate, sorbic acid, and potassium sorbate

**Some oral liquids can be self preserving, like syrups and alcohols at high concentrations, but preservatives are added anyway. **

Solution packaging and storage

• Packaged in:
• Prescription bottles
• Spray bottles
• Nebulizer dispensers
• Roll-on applicators
• Parenteral containers like vials or IV bags
• Storage requirements vary for each solution, so pay attention!
• Some require refrigeration
• Always avoid extreme cold and hot temperatures (extreme cold can cause precipitation)

Solution BUD

• Beyond Use Date
• Indicates specific stability information regarding the length of time that a solution is good for before it needs to be discarded
• USP <795> provides default maximum BUD
• Non preserved aqueous oral/topical solutions: 14 days refrigerated
• Preserved oral/topical aqueous solutions: 35 days refrigerated or RT
• Non-aqueous oral solutions: 90 days refrigerated or RT