Dosage Lec - Module 1

Container

Holds the pharmaceutical article and may be in direct contact with it

Immediate Container

Container that is in direct contact with the article at all times

Well-Closed Container

Protects contents from extraneous solids and from loss of article under ordinary conditions

Tight Container

Protects contents from contamination, loss, efflorescence, deliquescence, evaporation; capable of tight re-closure

Hermetic Container

Impervious to air or gas under normal handling, shipping, storage, and distribution

Examples of Hermetic Containers

Ampoules, vials, and glass containers sealed against air

Light-Resistant Container

Protects from light degradation by reducing transmission

Amber

Another term for light-resistant container

Light resistant opaque plastic

Plastic or glass that reduces light transmission for light-sensitive pharmaceuticals

UV Absorbers

Agents added to decrease transmission of short ultraviolet rays

USP Standard for Light Transmission

Not more than 10% transmission between 290–450 nm

Tamper-Evident Packaging

Packaging with one or more indicators/barriers to entry; if breached indicates tampering

Film Wrapper

Film sealed around product/container; film must be cut or torn

Blister Pack

Individually sealed dose units; requires tearing/breaking individual compartments

Bubble Pack

A kind of tamper evident packaging where product and container are sealed in plastic, usually mounted on display card; plastic must be cut or broken open to remove the product.

Shrink Seal

Plastic/film shrunk by heat/drying to conform to cap; must be torn to open

Pouch

Sealed individual packet; must be torn to reach product

Tape Seal

Paper/foil sealed over carton flap or bottle cap; must be torn/broken

Bottle Seal

Paper/foil sealed to mouth of container under cap

Breakable Cap

Plastic/metal cap that must be broken to remove

Tube Seal

Seal over mouth of tube; must be punctured

Carton Seal

Carton flaps sealed; cannot be opened without damage

Child-Resistant Container

Difficult for children <5 years to open or obtain harmful contents

Single-Dose Container

Holds a quantity of drug intended as single dose

Examples of Single-Dose Containers

Ampoules, prefilled syringes

Multiple-Dose Container

Permits withdrawal of successive portions without changing strength or purity

Example of Multiple-Dose Container

Multidose vial

Polyvinyl Chloride (PVC)

Rigid, good clarity, used in blister packs; unsuitable for gamma sterilization

Polypropylene, Polyethylene terephthalate (PET)

Plastics with excellent transparency and can be sterilized by gamma radiation

Glass Type I

Borosilicate glass, highly resistant, used for parenterals

Glass Type II

Treated soda-lime glass, resistant to water attack

Glass Type III

Soda-lime glass, suitable for dry powders

Glass Type NP

General-purpose soda-lime glass for non-parenteral use

Advantages of Plastic

Lightweight, unbreakable, variety of shapes, compatible with many drugs, low cost

Disadvantages of Plastic

Permeability, Leaching, Absorption, Light Exposure, Deformation

Cold Storage

Temperature not exceeding 8 °C

Refrigerated Storage

2–8 °C

Freezer Storage

-25 °C to -10 °C

Cool Storage

8–15 °C

Room Temperature

20–25 °C

Warm Temperature

30–40 °C

Excessive Heat

Above 40 °C

Master Formula

refers to the formulation that best meets the goals for a finished product.

Purity of Chemical Substance

Product appearance essential for evaluation of properties

Chemical Properties

Structure, form, reactivity

Physical Properties

Particle size, crystalline structure, melting point, solubility

Biologic Properties

Ability of drug to reach site of action and elicit response

Microscopic Examination

Indicates size distribution and crystalline form

Melting Point

Detects impurities; changes melting point and solubility

Phase Rule

Relates independent variables (temperature, pressure, concentration) to phases in equilibrium

Particle Size Effects

Influences dissolution rate, bioavailability, stability, sedimentation, flow

Polymorphism

Ability of drug to exist in different crystalline forms with different properties

Solubility

Drug must have adequate solubility for therapeutic effect

Dissolution Rate

Rate at which drug dissolves in absorption site fluids

Membrane Permeability

Drug must cross biologic membrane to act

Passive Diffusion

Process by which lipid-soluble drugs cross membranes

Partition Coefficient

Measure of drug lipophilicity

Stability Studies

Physical, chemical, biological stability evaluated before formulation

Hydrolysis

Drug breakdown due to reaction with water

Oxidation

Drug degradation due to loss of electrons

Stability

Extent product retains properties throughout storage period

Chemical Stability

Drug retains chemical integrity and potency

Physical Stability

Appearance, palatability, uniformity, dissolution, suspendability maintained

Microbiological Stability

Antimicrobial agents retain effectiveness

Therapeutic Stability

Therapeutic effect remains unchanged

Toxicological Stability

No significant increase in toxicity

Reasons for Stability Testing

Ensure efficacy, safety, shelf life

Antioxidants

Added to enhance stability against oxidation

Flavoring Agents

Mask taste; improve palatability

Sweet Flavors

Preferred by children

Tart Flavors

Preferred by adults

Cyclamate

Artificial sweetener banned by FDA in 1969 due to carcinogenicity concerns

Acesulfame Potassium

Non-nutritive sweetener, 130× sweeter than sucrose, used in gums, coffees

Aspartame

Artificial sweetener contraindicated in PKU due to phenylalanine content

Stevia

Natural sweetener, 30× sweeter than sucrose, non-toxic and safe

External Use Colorants

Restricted to external parts of body (not lips/mucosa)

Tartrazine

FD&C Yellow No. 5; Synthetic dye; may cause allergic reactions, cross-reacts with aspirin allergy

FD&C Lake

Pigments made from dye adsorbed on alumina hydrate; suitable for low-moisture formulations

Alcohol Vehicles

Self-sterilizing dosage forms, no preservatives needed

Aqueous Vehicles

Provide good microbial growth medium (require preservatives)

Ophthalmic Preservatives

Low-irritant preservatives used in eye drops (e.g., benzalkonium chloride, chlorobutanol, thimerosal)

Amaranth

FD&C Red No. 2; used extensively in drugs, cosmetics and foods. Causes cancer in rats.

Cocoa-flavored vehicles

Effective for masking the bitter taste of the drugs.

Fruits or citrus flavor

Combats sour/acid taste of the drugs.

Cinnamon, orange, raspberry

Makes salty tasting drugs more palatable.