Pharmaceutics II: Exam 1

What is the definition of pharmaceutics?

the study of formulating a drug/chemical entity into a dosage form for optimal delivery, stability, pharmacology and patient compliance

What is the definition of pharmacokinetics?

• “What the body does to the drug”

• the study of Absorption, Distribution, Metabolism and Excretion (ADME) of the drugs

• includes factors that influence ADME

What is a drug substance?

an active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body, but does not include intermediates used i the synthesis of such ingredient

What is a drug product?

a finished dosage form, such as a tablet, capsule, or solution that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients

What is a drug substance also known as?

• Active pharmaceutical ingredient (API)

• different forms (salts, hydrates, solvates)

Why do we need drug products (dosage forms)?

• small doses (quantities)

• physical form (solid, semisolid, liquid)

• route of administration, intended use (suppositories)

• improve API stability

• improve bioavailability

• modify drug release

• target drug release

• patient compliance (handling, storage, administration)

What is micromeritics?

it is the science of small particles, and includes particle size and size distribution, shape, densities, porosity, flowability, compressibility, etc.

What is properties of a drug are impacted by the particle size, shape and distribution of a dosage form of a drug?

• disintegration

• dissolution

• content uniformity

• suspendability

• compressibility

How does one measure the PS of a non-spherical particle?

• estimate using ‘equivalent’ diameter

  • calculate the diameter of a sphere with equivalent geometry or physical properties to the particle in question

  • e.g. projected area, surface area, volume, sedimentation rate, aerodynamics diameter etc.

How does one analyze the PSD of a non-uniform powder?

• collect particle size data from a representative sample (volume, weight, etc.)

• plot frequency of occurrence vs. size

  • plot is called a histogram

• report

  • distribution

  • average/mean particle size

  • d50 or d90

What are commonly used methods for particle size analysis?

• sieving (USP 786)

• optical microscopy (USP 776)

• light diffraction (SUP 429)

What does method of choice depend on for particle size analysis?

• particle size range

• purpose and application

• equipment availability

What are the characteristics of Optical microscopy?

• sample size: small (mg)

• sample prep: dry or wet

• size range: 1 mm to 2,000 mm

• analysis time: very slow

• mechanism of measurement

  • direct observation is only mechanism of measurement

  • measures length or projected area

• Operator training essential

What are the characteristics of sieving?

• sample size: large (up to 50 g)

• sample prep: typically dry

• size range: 25 mm to 2,000 mm

• analysis time: ~20 min/sample

• mechanism of measurement

  • material passing through aperture

  • measures dimension that pass through orifice

• Operating parameters essential

What is the US Sieve No. (mesh number)?

the number of openings per linear inch

What happens as the sieve number increases?

the particle size decreases, becomes finer

What are the characteristics of light diffraction/scattering?

• sample size: variable mg to g

• sample prep: dry or wet

• size range: 0.05 mm to 2,000 mm

• analysis time: 1<min/sample

• mechanism of measurement

  • measures volume

  • operator training essential

• scattering angle 0 alpha to particle size

What is the descriptive term for a particle that has a d50 of > 355 and a sieve no. of 45?

coarse

What is the descriptive term for a particle that has a d50 of 180-355 and a sieve no. of 80-45?

moderately fine

What is the descriptive term for a particle that has a d50 of 125-180 and a sieve no. of 120-80?

fine

What is the descriptive term for a particle that has a d50 of greater than or equal to 125 and a sieve no. of 120?

very fine

What are ways to reduce particle size?

• increase in surface area

• small scale

  • trituration

  • levigation

• large scale

  • milling

  • pulverization

What are particle/powder densities characteristics?

• Density (p) = mass/volume

• mass (weight) of a powder can be measured easily, and is standard

• what about the volume? Which volume?

  • bulk volume or loose volume

  • tapped volume

  • true volume

What can bulk volume be described as?

the volume measured before tapping out the air pockets between particles.

*this volume will always be more than the tap volume

What can tap volume be described as?

the volume after the air pockets are removed from tapping

What is the impact of particle/powder densities on dosage forms?

• dosage accuracy

• manufacturing/compounding

How can the flow of powder be improved?

• by excipients: glidants and lubricants

• granulation

What is powder flow analysis?

• Carr’s compressibility index (CI)

• CI = (tapped density-loose density)/tapped density x 100

What is the flow property of a powder than had a compressibility index (%) of less than or equal to 10 and an angle of repose (degrees) of 25-30?

excellent

What is the flow property of a powder than had a compressibility index (%) of 11-15 and an angle of repose (degrees) of 31-35?

good

What is the flow property of a powder than had a compressibility index (%) of 16-20 and an angle of repose (degrees) of 36-40?

fair (aid not needed)

What is the flow property of a powder than had a compressibility index (%) of 21-25 and an angle of repose (degrees) of 41-45?

passable (may hang up)

What is the flow property of a powder than had a compressibility index (%) of 26-31 and an angle of repose (degrees) of 46-55?

poor (must agitate, vibrate)

What is the flow property of a powder than had a compressibility index (%) of 11-15 and an angle of repose (degrees) of 56-65?

very poor

What is the flow property of a powder than had a compressibility index (%) of >38 and an angle of repose (degrees) of >65?

very, very poor

What is a definition of a powder?

a dry substance composed of finely divided particles

What are the pharmaceutical applications of powders?

• bulk form of most APIs and excipients

• dosage form

What are examples of powders?

• lactose, microcrystalline cellulose

• Renvela (sevelamer carbonate)

• MiraLAX (PEG 3350)

What are granules?

agglomerates of powder particles

What are the pharmaceutical applications of granules?

• processing intermediates for tablets and capsules

• dosage form

What are examples of granules?

• Biaxin (Clarithromycin)

• Mucinex Children’s Mini-melts Packets

What is the difference between powders and granules?

• particle size and shape

• Bulk properties (flowability, density)

• manufacturing processing

  • pharmaceutical granulation

• often used interchangeably (should not be in the pharmacy world)

What are examples of powders as dosage forms?

• oral powders

• dusting powders

• aerosol powders

• sterile powders

• dentifrice powders

• douche powders

• packaging

  • bulk powders

  • divided powders (packet or sachet)

What are characteristics of oral powders?

• to be dissolved or suspended in water or foods

• available in bulk and divided powders

What are examples of oral powders?

• Psyllium

• Cholestyramine

• Cefdinir

What are Effervescent oral powders?

• to be dissolved in water-releasing CO2

• key excipients: sodium bicarbonate, citric acid, and tartaric acid

What are examples of effervescent oral powders?

• Emergen-C

• Eboost

• FizzMix base from Medisca

What are the advantages of oral powders?

• stability

• dose adjustment

• easy to swallow

• bioavailability

What are the disadvantages of oral powders?

• vehicle

• time

• accuracy

• taste

What are dusting powders?

• topical applications to intact or broken skin

• not intended for systemic effect

• powder vehicle-starch and talc

What are the desirable qualities for dusting powders?

• fine, separated particles (125-180 micrometers)

• ease of flow and spreadability

• adhere to skin

• good covering and adsorptive properties

What are examples of dusting powders?

• Lamisil

• Gold Bond

What are aerosol powders for?

• for inhalation

  • local and systemic

  • require a narrow range of particle size

  • special devices-to be covered later

• for various body surfaces or cavities

  • nose, throat, tooth socket, and skin

  • apply with a powder blower or an insufflator

What are sterile powders used for?

• for injections

• powder or freeze-dried (lyophilized) cake

• reconstituted prior to use

• unique properties-to be covered later

What methods can be used for powder mixing on a small scale (blending)?

• Trituration

• Spatulation

• Sieving (sifting)

• Tumbling

• New tools

• Turbula Mixer

• Resonant Acoustic Mixer (RAM)

What are methods of powder mixing on a large scale?

• Tumble mixer

• Agitator mixer

How does one achieve a homogenous mix for powder mixing?

• uniform particle size and density

• particle movement (1/2 to 2/3 full)

• avoid segregation

What are the characteristics of powder sampling?

• sample size/number

• location

• tools

  • sample thief

  • in-line samplers

How does one to mix a small amount of a potent drug with a large amount of diluent?

• use geometric dilution

  • assuming the ratio of components is at least 3:1

  • stepwise approach-equal amount of the two ingredients

• additional tips

  • color indicators

  • commercial “dilutions”

What is the definition of capsules?

solid dosage forms in which the drug or a drug formulation is enclosed within either a hard or a soft soluble shell

What are the applications of capsules?

• oral

• granules (disperse with food/drink)

• DPI/vaginal/rectal

• GI imaging

What are the characteristics of hard gelatin capsules?

• hard shell

• two piece

What are the characteristics of soft gelatin capsules?

• soft shell

• one piece

What are the capsule fill contents of hard gelatin capsules?

• powder and granules

• MR beads and pellets

• liquids and semi-solids

• small tabs/caps

What are the fill contents of soft gelatin capsules?

• liquids

• semi-solids

What are the major components of capsule shell materials?

• gelatin-hard and soft capsule shells

• HPMC-hard capsule shells

What are the minor components of capsule shell materials?

• water

• plasticizers (glycerin)

• preservatives (parabens)

• colorants

• opaquants (opacifiers)

• extended-release materials

What are gelatin capsule shells most commonly made up of?

hydrolyzed collagen of connective tissues

What are the advantages of hydrolyzed collagen of connective tissues?

• good film forming material

• non-toxic and acceptable in most countries

• soluble in warm GI fluids and broken down by enzymes

What are the disadvantages of hydrolyzed collagen of connective tissues?

• animal origin

• stability

• may contain 13-16% moisture (moisture transfer)

What are HPMC capsules made of and who are they primarily for?

hydroxypropyl methylcellulose used typically by vegan patients

What are the advantages of HPMC capsule shells?

• plant derived

• dissolution-pH and temperature independent

• low moisture content

• chemically more stable than gelatin

What are the disadvantages of HPMC capsule shells?

• production

• cost

What are hard shell capsule designs?

• pre-made shells

  • standard shapes and sized

• ready for manufacturing or compounding

What is the tampered rim on the body of a capsule for?

to engage easily with the cap for problem-free closure

What are the six elongated dimples on a capsule for?

maintain precise round capsule diameter, improving filling machine performance

What are the rounded hemispherical ends on a capsule for?

mechanically stronger and more resistant to deformation

What are the locking rings on a capsule for?

provide a full-circumference leak-free closure

What are the two aerodynamic air vents for?

allow air to escape from the cap; critical when operating high speed filling machines

What are characteristics off pre-locked position?

• dimples of the cap engage gently with the indented ring of the body

• empty capsules stay closed in transit; yet the consistent low pre-lock force reduces opening and rectification problems

What are the characteristics of the sealed position?

• the full-circumference locking rings of the cap and the body interlock to form a secure, leak-free closure

• a wide choice of capsule sizes are available that are compatible with all types and models of capsule filling machines

What shape is this capsule?

Pulvule

What shape is this capsule?

Spansules

What shape is this capsule?

DBcaps Over-Encapsulation Capsules

What shape is this capsule?

Sprinkle capsules

What are banding on capsules for?

• for preventing tampering

• gelatin seal around capsule at the seam of the body and cap

What are the human hard shell capsule sizes?

000, 00, 0, 1, 2, 3, 4, and 5

What are the veterinary hard shell capsule sizes?

Su07, 07, 10, 12el, 11, 12, and 13

What happens to the size of the capsule as the size number increases?

the capsule size decreases

What are soft shell capsule designs?

• various shapes possible

• shells are not pre-made

  • form-fill-seal in one step

• requires special equipment and trained operators

  • contract manufacturing

  • not for compounding

What are the applications of soft shell capsules?

• Oily substances

  • vitamin E

  • isotretinoin (Acutane, a retinoid)

  • Dronabinol (Marinol)- active in Marijuana

• sometimes used to enhance bioavailability

  • cyclosporine (Neoral vs Sandimmune)

  • Digoxin

What is the function of a diluent or filler?

provide bulk and cohesion

lactose, microcrystalline cellulose, starch, and dibasic calcium phosphate are example of what?

diluent or filler

What is the function of disintegrant?

break up and disperse capsule contents

pregelatinized starch, croscarmellose sodium, and sodium starch glycolate are examples of what?

disintegrant

What is the function of a glidant?

improve powder flow

silicon dioxide and talc are examples of what?

glidant

What is the function of lubricant?

prevent sticking

magnesium stearate and stearic acid are examples of what?

lubricants

What is the function of surfactants?

enhance wetting