Excipients (23)

What is an excipient?

an inactive substance that serves as the vehicle or medium for a drug or other active substance.

What is the purpose of using excipients?

To achieve accurate dosing form, support organoleptic profile, to have consistency in drug release and bioavailability, stability, ease of administration, and to produce an efficacious drug product

Give some examples of excipients

Coloring, sweetening, flavoring, solubilizing, thickening, suspending, and binding agents, antioxidants, preservatives, surfactants, solvents, and lubricants

What are ideal characteristics of excipients?

Non-toxic, pharmacologically inert, non-reactive, and do not interfere with the stability of the drug

What does GRAS stand for?

generally recognized as safe

Describe GRAS

Any substance intentionally added to food is a food additive and subject to premarket review and approval by the FDA. Serves as a review process for new substances such as preservatives, colors, flavoring agents, etc.

What are organoleptic properties?

odor, color, taste, flavor, appearance, and palatability

What is the rationale behind organoleptic properties?

Using pharmaceutical coloring agents to match flavor expectations increases patient acceptability

What is flavor selection and what is it based on?

Choosing a flavor that will mask drug bitterness and to make a formulation more palatable.

What are some characteristics of a good flavoring agent?

Immediate flavor identity, acceptable mouthfeel, and short aftertaste

How does increasing the number of hydroxyl groups affect the taste of a medication?

Makes it sweeter

Give some examples of volatile compounds that are pleasant to the taste and contribute to odor and flavor.

Esters, alcohols, and aldehydes

Flavors can be consisted of what type of carriers?

Oil-soluble, water-soluble, and dry powder carriers

Give examples of oil-soluble carriers

soybean and other edible oils

Give examples of water-soluble carriers

Water, ethanol, propylene glycol, and glycerin

Give examples of dry carriers

Corn syrup solids, sugars, and whey protein

Are liquid medications normally flavored?

Yes, to mask an undesirable taste

Are coated tablets or capsules usually flavored?

No, no contact between the tongue and drug

Are chewable tablets usually flavored

Yes

What are four categories of taste?

Sweet, sour, salty, and bitter

What is umami?

A category of taste in food corresponding to the flavor of glutamates

Describe salty tasting compounds

Presence of cations and anions together such as NaCl

Describe sweet tasting compounds

Large presence of hydroxyl groups such as sucrose

Describe sour tasting compounds

Presence of H+ such as citric acid

Describe bitter tasting compounds

High molecular weight salts such as caffeine

Give two examples of natural sweeteners

Sucrose and Sorbitol

Why is sucrose not recommended for pediatrics

It is cariogenic and calorific

Sorbitol can cause?

Diarrhea

Give an example of an artificial sweetener

Aspartame

What does aspartame break down into once in the body?

Phenylalanine, aspartic acid, and methanol

Why is aspartame not recommended in those who have phenylketonuria (PKU)?

Those with PKU can not efficiently break down phenylalanine and ingestion of aspartame can increase phenylalanine in the body, causing initial issues like nausea, vomiting, etc Then severe/long term issues like mental retardation, CNS damage, and hypopigmentation

What is more preferable to use: sucrose, saccharin, or aspartame?

Saccharin

Why is saccharin favored over sucrose and aspartame?

It is more stable, no calories, and more sweet

What are some issues that can be presented when using saccharin?

It has a more bitter taste and aftertaste compared to sucrose and aspartame

What is the main purpose for coloring agents?

Esthetic purposes

Most pharmaceutical colorants are _______

synthetic

Give an example of a naturally sourced colorant

Red ferric oxide mixed in small proportions with zinc oxide powder to give calamine a pink color

What pharmaceutical products do not contain colorants?

Ointments, ophthalmic solutions, and parenteral products.

Certified color additives are classified according to their approved use, what are the three classifications?

FD&C color additives, D&C color additives, and External D&C color additives

FD&C color additives

Used in foods, drugs, and cosmetics

D&C color additives

Used in drugs, cosmetics, and some medical devices

External D&C color additives

restricted to external parts of the body (not including the lips and other parts that are covered by mucous membrane)

What are two solutions that undergo sterilization preparation?

Ophthalmic and injectable solutions

What do many sterile solutions require in order to maintain their aseptic condition?

An antimicrobial preservative

What IV preparations are not required to have an antimicrobial preservative?

Large volumes that work as replenishers or as nutrients

What are some preparations that do not need to undergo sterilization preparation?

Aqueous solutions such as syrups, emulsions, suspensions, and some semisolid preparations like creams

What aqueous may not be required to have an antimicrobial preservative?

Hydroalcoholic and most alcoholic preparations (alcohol acts as the preservative) such as elixirs, spirits, and tinctures

What is the mode of action of preservatives?

They interfere with microbial growth, multiplication, and metabolism

What are four classifications of excipients based on origin?

Animal source, vegetable source, mineral source, and synthetic

Give examples of animal source excipients

Lactose, gelatin, bees wax, honey, lanolin, etc

Give examples of vegetable source excipients

Starch, peppermint, turmeric, etc.

Give examples of mineral source excipients

Silica, talc, kaolin, etc.

Give examples of synthetic source excipients

Saccharin, polyethylene glycols, polysorbates, etc.

What are three classifications of excipients based on function?

Solid dosage form, liquid dosage form, and semisolid dosage form

What are the categories of solid excipients?

Diluents, binders and adhesives, lubricants, glidants, disintegrants, superdisintegrants, coloring agents, flavors, sweeteners, sorbents, coating materials, and plasticizers

Diluent function and working principle

Function: Act as a filler

Working principle: make up the bulk of solid unit dosage form when the drug itself is not enough to produce the bulk

Binders/adhesives function and working principle

Function: to hold various powder particles together, creating cohesion and allowing for the formation of a stable, unified structure

Working principle: improve free flow qualities by creating granules of the desired size and hardness

Lubricants function and working principle

Function: To reduce inter-particular friction between powders that allows for easier formulation of tablets (don't stick to surface of die and punches)

Working principle: Creates a film of low shear strength at the interface of tablet mass and die wall

Glidants function and working principle

Function: Improve flow characteristics of powders

Working principle: Add to the dry state before compression and reduces friction between particles

Disintergrants function and working principle

Function: Facilitate breakup or disintegration after administration

Working principle: Draws water into the tablet, swells tablet, and causes the tablet to burst

Superdisintergrants function and working principle

Function: Improve disintegrants efficacy

Working principle: Draws water into the tablet, swells tablet, and causes the tablet to burst

Coloring agents function and working principle

Function: Impart aesthetic appearance to dosage form

Working principle: NA

Flavor function and working principle

Function: Limited to chewable tablets/tablets intended to dissolve in the mouth

Working principle: Mask unpleasant taste

Sweetener function and working principle

Function: Add sweet taste to the formulation

Working principle: NA

Sorbent function and working principle

Function: Moisture proofing

Working principle: Limits the take up of liquid or gas either by adsorption or absorption in the dry state

Coating materials function and working principle

Function: Protect tablet ingredients from deterioration by moisture, help in swallowing unpleasant tasting tablets

Working principle: NA

Plasticizers function and working principle

Function: Used for soft gelatin capsule preparation, gelatin based suppositories, and film coated tablets

Working principle: Produce elasticity and flexibility to the coating materials of tablets, determine hardness of capsule in gelatin capsules, and impart softness and resilience to suppositories

What are oro-dispersible tablets (ODT)?

Dispersible tablets that rapidly disintegrate without chewing, when placed on top of the tongue. No water required.

What are the two main types of ODTs?

lyophilized units and conventional tablets

Describe lyophilized units

Carrier excipient- predominately sucrose, disintegrate < 5 seconds, only low drug loading is possible (5-10mg), and is prone to friability so packed into blisters

Describe conventional tablets

Disintegration time varies, larger drug loading is possible (up to 500mg), more robust- can pack into blisters or bottles, and can involve novel/conventional/combination excipients.

What are the categories of liquid excipients?

Solvents, co-solvents, buffers, antimicrobial preservatives, antioxidants, wetting agents, antifoaming agents, thickening agents, humectants, chelating agents, emulsifying agents, flocculating agents, sweetening agents, colors, flavors, and excipients used in aerosol propellant

Solvents function and working principle

Function: dissolving solutes and active ingredients

Working principle: Breaking bonds and reducing effective charge on ions, increasing solute-solvent interactions

Co-solvents function and working principle

Function: Increase the solubility of solute in solvents

Working principle: Reduces interfacial tension between aqueous solutions and hydrophobic particles and vice versa

Buffers function and working principle

Function: Maintain pH of the formulation

Working principle: Act by binding to hydrogen ions in low pH or donating hydrogen ions in high pH

Antimicrobial preservatives function and working principle

Function: Prevent microbial growth

Working principle: Bacteriostatic action

Antioxidants function and working principle

Function: Control oxidation

Working principle: Get preferentially oxidized or by blocking an oxidative chain reaction

Wetting agents function and working principle

Function: Aid wetting and dispersion of hydrophobic active ingredients

Working principle: Reduce interfacial tension between solids and liquids in suspensions

Antifoaming agents function and working principle

Function: Discourage formation of stable foam

Working principle: Lowers surface tension and cohesive binding of liquid phase

Thickening agents function and working principle

Function: Prevent settling/sedimentation, modify viscosity

Working principle: Entrap solid particles

Humectants function and working principle

Function: Retard evaporation of aqueous vehicles from dosage forms

Working principle: Their hygroscopic nature prevents evaporation

Chelating agents function and working principle

Function: Protect drug from catalysts that accelerate oxidative reactions

Working principle: Form complexes with metal ions

Emulsifying agents function and working principle

Function: Prevent coalescence of dispersed globules

Working principle: Forms barriers at interface and reduces interfacial tension

Flocculating agents function and working principle

Function: Prevent caking

Working principle: Addition of electrolyte reduces the magnitude of zeta potential of dispersed molecules

Sweetening agents, colors, and flavors functions

Add sweetness, add color, add flavor

Excipient in aerosol propellent function and working principle

Function: Develops pressure in container that will expel the product

Working principle: NA

What are the categories of semisolid excipients?

Structure-forming excipients, preservatives, antioxidants, solubilizers, gelling agents, emollients, and suppository bases

Structure-forming excipients function

Forms a gel-like structure

Preservatives function

Preserving the formulation

Antioxidant function

Prevent oxidation

Solubilizer function

Enhance solubility

Gelling agents function

Form gels

Emollients function

Modify vehicle/skin characteristics to assist penetration of active ingredient through the skin

Suppository bases function

Used to form base for dissolving active ingredient

Give an example of two excipients that are incompatible with each other and what they produce

Gelatin and plasticizer. Produce soft gelatin capsule

What are four package-excipient interactions you should be aware of?

Glass, plastic, metal, and rubber packaging

What are some interactions that can occur with excipients and glass containers?

Leaching of alkali, interactions with oxides on glass container, and oxidative reactions due to glass present.

Leaching of alkali

Can change the pH of the formula

How can oxides present on glass containers alter excipients?

Can alter the physical and chemical stability of the formulation

Give an example of oxidative reactions that can occur because of a glass container and the consequences

Iron and manganese oxide cations can catalyze oxidative reactions and can cause decomposition