simple liquid dosage forms

what is simple (monophasic) liquid dosage forms?

homogenous (single-phase) preparations where the active drug is completely dissolved in a liquid vehicle. commonly used for oral administration, as well as topical and specialized uses.

what is complex (multiphasic) liquid dosage forms?

pharmaceutical preparations containing two or more immiscible (unmixable) phases, where one phase is dispersed throughout the other.

• unlike single-phase solutions, multiphasic liquids contain insoluble active ingredients

• require special stabilizing agents to ensure the active ingredients are evenly distributed, at least temporarily, before administration

why would we use a non-aq solution?

if the drug has poor solubility in water

what are suspensions, emulsions, and colloids?

suspensions - particles in water

emulsions - oil in water

colloids - extremely fine particles in liquid (hard to see)

how are monophasic solutions used? (dosage forms-wise)

topical, oral, ophthalmic, nasal…

how to classify monophasic solutions based on composition?

• syrups

• elixirs

• tinctures

• spirits

• aromatic waters

• liniments

• collodions

how to classify monophasic solutions based on pharmaceutical solution?

• contains drug in a suitable solvent, and

• other inactive ingredients: color, flavors, sweeteners, stability enhancers etc.

what are the advantages of solutions?

• compliance: improved compliance (by using flavors and colors)

• bioavailability problems: less bioavailability problems compared to many other dosage forms

  • for liquid solutions, the drug is already dissolved, so it is immediately available for absorption

    • no bioavailability issues (because there’s no dissolution/solubility issues of the drug)

• enteral feeding is provided in solution or emulsion forms

• ease of administration: ease to those individuals with difficulty swallowing solid dosage forms (pediatric or geriatric)

• dose variation: homogenous, therefore, less dose variation compared to suspension and emulsion

what are the disadvantages of solutions?

• stability: least stable of all dosage forms

  • this is because the drug is dissolved in water

    • chemical reactions in liquid are highly favorable, so there is a higher chance of things dissolving quickly, making it more prone to reactions like hydrolysis in water

• microbial growth: usually preservation is required

• solubility: some drugs are poorly soluble

• light sensitivity: often need to protect solutions from light

• transport & storage: bulky, not easily transportable

• manufacturing: often more expensive to manufacture

when trying to formulate solutions, what do you need?

• drug

• solvent

• preservative

• sweetener

• thickener, viscosity enhancer

• color

• flavor

• antioxidant

• buffer

• surface active agent (surfactants)

• tonicity modifier (NaCl)

what is tonicity modifier?

• hypertonic solution: the cell shrinks

• hypotonic solution: the cell swells

• isotonic solution: normal cell

to choose the right things for a solution, what needs to be in a solvent?

• dissolution power

  • must have the right power to dissolve the drug

• clarity

  • when drug dissolves, it must be clear (no cloudiness)

• toxicity

• compatibility

  • compatible to physiological fluids in the body

• palatability, color, odor

• price

  • not too expensive

what are the solvents for pharmaceutical use?

• water is commonly used

  • auxiliary solvents (alcohol, glycerin and propylene glycol) may be added

    • if the drug is not dissolvable in water, we use the auxiliary solvents to help dissolve the drug in water

• organic solvents - acetone, isopropyl alcohol - too toxic for internal use

  • useful as solvents in drug development research

• fixed oils - corn oil, cotton seed oil, peanut oil and sesame oil may be used as solvents, particularly for oleaginous injections

  • fixed oils mean that when kept at room temp, it will not evaporate

what is the list of solvents for pharmaceutical use?

• purified water, USP

• alcohol, USP

• diluted alcohol, NF

• rubbing alcohol

• isopropyl rubbing alcohol

• glycerin, USP

what are oral solutions?

• drug is completely dissolved, usually contains sweetener, colorant, flavoring agent and preservative

• for extemporaneous preparation, information about solubility and stability is crucial

• sometimes supplied as dry mixtures to be reconstituted, for ingredients with poor aq stability e.g. Penicillin V Potassium for Oral Solution

what are syrups?

concentrated aq preparations of sugar or sugar substitute with or without medicinal agent and flavoring agent

• sweet and viscous

  • because sugar amount is so high, it makes it thick

• sucrose (60-80% maximum 85%)

• flavored or unflavored (cherry, cocoa, simple)

• used to mask taste and odor of liquid medications

what are the components of syrups?

1. purified water, USP

2. sugar (sucrose) or substitutes

• substitutes: sorbitol and glycerin, dextrose, non-glycogenic methylcellulose (sweetness + viscosity)

3. antimicrobial preservative if needed:

• benzoic acid 0.1-0.2%

• methylparaben, propylparaben 0.1%

4. flavorants: FDA approved, volatile oil, vanillin

5. colorant: FDA approved, water soluble, non-reactive, stable

• simple syrup NF syrup (stable, crystallization resistant) - sucrose 85% w/v

  • no preservative required because the sugar amount is so high (85% sugar), whatever water was added was all taken up by sugar

what is the role of alcohol in antihistamine syrup?

a) co-solvent

b) solvent

c) sweetening agent

d) preservative

a

antihistamine syrup

what is sodium benzoate considered?

preservative

antihistamine syrup

what is syrup considered?

sweetening agent

antihistamine soup

what is sorbitol solution considered?

sweetening agent

antihistamine syrup

what is purified water considered?

solvent

antihistamine soup

what is chlorpheniramine maleate considered?

drug

antihistamine syrup

what is glycerin considered?

sweetening agent and does viscosity

antihistamine syrup

what is alcohol considered?

co-solvent

what are the methods of syrup preparation?

1. solution with the aid of heat

2. agitation without heat

3. addition of sucrose to a prepared medicated liquid

4. percolation of medication or sucrose

1. solution with the aid of heat

quickest method of preparation

• used for thermostable medications and non-volatile materials

• sugar is generally added to the purified water, and heat is applied until the sugar is dissolved

• then, other heat-stable components are added to the hot syrup

• the mixture is allowed to cool, and its volume is adjusted to the proper level by the addition of purified water

what are the disadvantages with the method: solution with the aid of heat?

• sugar inversion: excessive heat should not be used to avoid inversion

  • i.e. hydrolysis of sugar - a disaccharide, into monosaccharides, dextrose (glucose) and fructose (levulose)

    • darkening in color due to invert sugar (caramelization)

      • makes it more sweet (but degraded sugar)

• sugar decomposed due to excessive heat is susceptible to microbial growth

• syrups cannot be sterilized by autoclaving

  • autoclaving is putting the material inside a stainless steel tank filled with water and heat the water with a high pressure so that the steam generated will kill the microbes

2. agitation without heat

• place all ingredients in a vessel larger than the volume of the syrup

• then agitate the mixture

  • at room temp

• time consuming but maximum stability

• medication dissolved in the minimum solvent then incorporated into the syrup

  • minimum solvent can be alcohol or glycerin and then add dissolved drug into syrup

disadvantage: slower than the solution with the aid of heat

3. addition of sucrose to a prepared medicated liquid

• used if medicated syrup is to be prepared from a tincture or a fluid extract

a) sucrose is added to the above medicated liquids and syrup is prepared

b) if the medicated liquid is soluble in water, then it is directly added to simple syrup or flavored syrup

• caution: alcohol-soluble components may precipitate upon addition to syrup

• heat is not required, hence produces a stable syrup

4. percolation

• purified water or the source of the medicinal component is passed slowly (percolated) through a bed of crystalline sucrose

• sucrose dissolves and forms a medicated syrup

• cylindrical or semi-cylindrical shaped percolator and course granular sucrose are used

  • this cylinder is packed with sugar crystals

    • the medicinal extract will flow through the cylinder. when it flows through the cylinder, it percolates into sugars. when it is percolating, some of the sugars will dissolve. once dissolved to bottom, you can add it back in and keep percolating until it dissolves into syrup.

• useful method when the source of the drug is a naturally occurring or plant based product

• ex: Ipecac Syrup

which of the following is the quickest method for preparation of a syrup involving a heat labile drug?

a) solution with the aid of heat

b) agitation without heat

c) addition of sucrose to a prepared medicated liquid

d) percolation

c

• heat labile means that the drug cannot handle heat so option a is out

• it says quickest

  • mixing without heat will take a long time

  • percolation involves having to make the “syrup” go through it multiple times to get it right

what does it mean for a drug to be heat labile?

it means that the drug is not stable to heat

what are elixirs?

clear, sweetened, hydroalcoholic solutions intended for oral use and are usually flavored to enhance their palatability

• elixirs are less sweet and less viscous than syrups

• main ingredients

  • alcohol, water, co-solvents (glycerin)

  • flavoring/sweetening agent (sucrose, glycerin, saccharin, volatile oils)

• elixirs are less efficient in masking taste than syrups

• elixirs have higher stability and are easier to prepare

what are the methods to prepare elixirs?

1. simple agitation

2. prepare alcoholic solution and aq solution then add aq to alcoholic

3. filter if needed

elixirs have two components: water and alcohol.

what is in elixirs?

• their alcohol content ranges from 5% - 40%

• self-preserving if alcohol content is more than 12%

  • no preservatives needed to be added is more than 12%

• alcohol content is a disadvantage for children

• small quantities of water and keep stirring into alcohol, and keep doing the process until appropriate amount has been added

  • incorrect: adding alcohol into water. the components of alcohol is exposed to water and if it happens to be insoluble in water, the alcohol will precipitate out

what are the types of elixirs?

• medicated

  • for therapeutic benefit

• nonmedicated

  • flavored vehicle for extemporaneous compounding or dilution of medicated elixirs

what are medicated elixirs?

• usually has one therapeutic agent for the ease of dose adjustment

• antihistaminic elixirs

  • basic amine prepared as salt (by interaction with acid)

  • pH is critical when diluted

ex: diphenhydramine HCl elixir

what are tinctures?

alcoholic or hydroalcholic solutions prepared from vegetable materials or chemicals

• contain alcohol 15 - 80% (for dissolution and preservation)

• tinctures differ by:

  • methods of preservation (percolation vs maceration)

    • maceration: the process of softening, breaking down, or extracting components from a substance by soaking it in a liquid

  • strength of drug

    • very high

  • alcoholic content

• mixing with other solutions may cause precipitation

• high alcoholic content - should be stopped and protected from high temps

• may contain light sensitive materials - should be stored in light resistant containers

which of the following dosage forms typically does not require a preservative?

a) tinctures

b) elixirs

c) syrups

d) oral solutions

a

• if over 12% alcoholic content, no need for preservative

  • is 15-80%