Phar430: Oral Solids Part II (Powders, Granules, lozenges, capsules)

Powder Flow Properties -important in mixing and blending of powders since powders should move past each other to be mixed -flow of powders can be classified as: 1. _______: usually characterized by "dustibility". For example, Talcum powder has dustibility value of 57& 2. ________: "sticky" property having reduced flow

1. Free flowing 2. Cohesive

Which of the following are disadvantages of powders and granules as dosage forms? CHOOSE ALL THAT APPLY A. bulk powders/granules are less convenient for patient to carry, and the masking of unpleasant taste may be a problem with powders B. bulk powders/granules are not suitable for administering potent drugs with a low dose because of variability involving spoon fill or level marks C. they are not suitable for administration of drugs which are inactivated or cause damage to the stomach D. powders and granules are not suitable for dispensing hygroscopic or deliquescent drugs

all of them are disadvantages

Generally, the largest size of capsule acceptable to patients is: A. 000 B. 5 C. 00 D. 1 E. None of the above

C. 00

The bloom strength of gelatin used for preparation of HARD gelatin capsules is: A. 150 g B. 500 g C. 200 g D. 100 g

C. 200 g

Particle Size Analysis: Which particle size analysis technique determines particle size by separating particles into various size ranges by successively increasing the velocity of the airstream in which they are carried? (based on the inertia of the particles) A. Light energy diffraction or dynamic light scattering B. Laser holography C. Cascade impaction

C. Cascade impaction

Which of the following properties BEST describes an efflorescent powder? A. absorbs moisture from air B. releases carbon dioxide when mixed with water C. contains water of hydration or recrystallization D. None of the above

C. contains water of hydration or recrystallization

The process of Lyophillization involves: A. atomization of drug solution via a nozzle followed by evaporation of solvent B. reduction of size by rubbing particles in a mortar or pestle C. freezing of aqueous solution or suspension followed by removal of water by sublimation D. use of heavy roller to crush mass

C. freezing of aqueous solution or suspension followed by removal of water by sublimation

Which of the following excipients is added to capsule powder as a LUBRICANT- for free flowing of powder mix or granules? A. lactose B. croscarmellose C. magnesium stearate D. sodium lauryl sulfate

C. magnesium stearate

Flow characteristics of powder are evaluated by indirect or direct methods. Indirect methods include ______ and _____

bulk density and angle of repose

Special Problems in Dispensing Powders: An _______ powder is a crystalline powder that contains water of hydration or crystallization -this water may be liberated during mixing or other manipulations and powder may become sticky/pasty or may liquefy (examples: codeine phosphate, atropine sulfate, caffeine, scopolamine hydrobromide)

efflorescent

Special Problems in Dispensing Powders: Problem: Some powders like camphor, menthol, lidocaine, and aspirin may become sticky, pasty, or may liquefy when mixed together and are called _________ mixtures

eutectic mixtures

Which of the following statements is TRUE about soft gelatin capsules? A. soft gelatin capsules do not contain a plasticizer B. soft gelatin capsules have higher bloom strength than hard gelatin capsules C. soften gelatin capsules are well suited for formulating volatile drugs as well as oils and low melting point (<75 C) drugs which cannot be compressed D. drugs subject to oxidative or hydrolytic degradation cannot be formulated in soft gelatin capsules

C. soften gelatin capsules are well suited for formulating volatile drugs

Disadvantages of Limitations of Capsules: Capsules cannot be used for administration of extremely ______ materials such as potassium chloride, potassium bromide, or ammonium chloride. Sudden release results in high concentrations leading to nausea and irritation to gastric mucosa.

extremely soluble

Soft Gelatin Capsules or Soft Elastic Capsules: The MOST commonly used plasticizer is ______

glycerol -sorbitol and propylene glycol are also used as plasticizers

Particle Size of Powders: U.S. Pharmacopeia (USP) terminology for powders: __________ typically fall in range of 4- to 12-sieve size, although granulations of powders prepared in 12 to 20-sieve range are sometimes used in tablet making

granules

Powders and granules are not suitable for dispensing _____ or _______ drugs. (i.e. Sodium valproate)

hygroscopic or deliquescent drugs Note: hygroscopic drugs: drugs that readily take up and retain moisture deliquescent: tending to absorb moisture from the air and dissolve in it.

Particle Size of powders influence a variety of important factors: 4. PENETRABILITY of inhaled particles: for deposition in to the deep respiratory tract the size suitable is 1-5 micrometers When particle size is reduced, the penetrability of inhaled particles is _________(improved or reduced?)

improved

Which of the following is true about the "Angle of Repose" in the context of powder flowability? A. the greater the angle of repose, the better the flowability of powder B. Carr's index is used to establish relationship between angle of repose and powder flowability C. the greater the angle of repose, the poorer the flowability of powder D. Both B and C are correct E. None of the above

C. the greater the angle of repose, the poorer the flowability of powder

Which of the following is TRUE when particle size of powders is reduced? A. the dissolution rate is decreased B. the suspendability is reduced C. the penetrability of inhaled particles in improved

C. the penetrability of inhaled particles in improved

What does the term micromeritics mean? A. a study of suspensions B. measurement of distance between two dosage forms C. the science and technology of small particles D. method to evaluate microbial contamination in parenterals E. None of the above

C. the science and technology of small particles

Characterization of Powder Flow: Indirect Methods: How is Bulk Density determined?

Carr's compressibility index derived from fluff density and tapped density is a simple method to evaluate the flowability of a powder (see image)

Particle Size of Powders: U.S. Pharmacopeia (USP) terminology for powders: ________ is the USP terminology when all particles of a powder pass through a No. 20 sieve and not more than 40% through a No. 60 sieve

Coarse (No. 20)

Which of the following are techniques used to prevent eutectic mixtures (becoming sticky, pasty, or liquefying)? A. keeping powders dry by adding a bulky adsorbent diluent such as light magnesium oxide or magnesium carbonate B. using a spatula for mixing instead of a mortar and pestle C. by first making the eutectic mixture and adsorb the mixture onto a bulky diluent D. All of the above

D. All of the above

Which of the following are advantages of powders and granules as dosage forms? A. solid powders are chemically more stable than liquids B. for drugs with a large dose (1-5 g), it is convenient to dispense as powder rather than tablets C. orally administered powders and granules have a faster dissolution rate than tablets or capsules D. All of the above

D. All of the above Note: orally administered powders and granules have a faster dissolution rate than tablets or capsules b/c the tablets/capsules have to first disintegrate before dissolution, whereas powders/granules are already more disintegrated

Hard gelatin capsules are made self-locking by forming indentations or grooves on the inside of the cap and body portions. Which of the following is an example of a SELF-LOCKING capsule? A. Pulvules B. Kapseals C. Spansules D. Coni-Snaps

D. Coni-Snaps -have air vents which allow air to escape during filling on high-speed capsule filling machines -can be used to fill a variety of substances such as granules, pellets, liquids, powders, etc. It is based on Snap-fit® construction which enables the two halves of the capsule shells to be positively joined through locking grooves in shell walls. Coni-Snap® capsules have tapered rim to avoid splitting (telescoping) and or denting of capsule shell, which is a common problem in capsules. Coni-Snap® Supro capsules are another design where the upper capsule part extends so far over the lower part that only rounded edge of the latter is visible. This makes separation of two parts more difficult. Greater capsule integrity.

Which of the following excipients is added to capsule powder to enhance wetting? A. lactose B. citric acid C. magnesium stearate D. sodium lauryl sulfate E. starch

D. sodium lauryl sulfate

_________ are agents used along with a toothbrush to clean and polish natural teeth. They are supplied in paste, powder, gel or liquid form -May be a form of bulk powder with soap or detergent or mild abrasive

Dentifrices

_______ powders completely dissolve in water prior to use as antiseptics or cleansing agents for a body cavity

Douche powders -most commonly intended for vaginal use, although may be formulated for nasal, otic, or ophthalmic use (E.g. Massengill Powder)

Which of the following is/are major differences between lyophillization and spray drying? A. the drug in aqueous solution is frozen at -40 C in lyophillization but not in spray drying B. spray drying involves atomization of drug solution by a nozzle C. spray drying process results in formation of spherical particles D. Only A and B E. A, B, and C

E. A, B, and C

________ granules contain sodium bicarbonate and either citric or tartaric acid and when dissolved in water, carbon dioxide is produced resulting in effervescence

Effervescent granules

Disadvantages of Limitations of Capsules: Capsules should not be used for highly ______ or ______ materials

Efflorescent or deliquescent -Efflorescent materials soften capsule when they lose moisture. -Deliquescent powders may dry capsule shell to excessive brittleness by extracting moisture from capsule shell.

Particle Size of Powders: U.S. Pharmacopeia (USP) terminology for powders: ________ is the USP terminology when all particles of a powder pass through a No. 60 sieve and not more than 40% through a No. 100 sieve

Fine (No. 60)

Particle Size of Powders: U.S. Pharmacopeia (USP) terminology for powders: ________ is the USP terminology when all particles of a powder pass through a No. 40 sieve and not more than 40% through a No. 80 sieve

Moderately coarse (No. 40)

Modern Techniques: ________ involves the atomization of the drug solution via a nozzle, followed by the evaporation of solvent by a current of circulating warm dry air

Spray drying -the particle size can be controlled by choosing a suitable atomizer -the product obtained is free-flowing, with almost spherical particles. especially convenient for tablet manufacture -this process is used for some powdered antibiotic formulations -spray drying is capable of producing spherical particles in range of 1-7 micrometers for dry powder inhalers -MOST USEFUL FOR THERMAL LABILE MATERIALS

Particle Size analysis: 1. Sieving--particles are passed by a series of sieves (range 40-9500 micrometers) 2. Microscopy--particles are sized through the use of a calibrated grid background (range 0.2-100 micrometers) 3. Sedimentation rate---particle size is determined by measuring the terminal velocity of particles through a liquid medium in a gravitational or centrifugal environment (range 0.8-300 micrometers). The sedimentation rate can be calculated from _______. (uses andreasen pipette)

Stoke's Law dx/dt=[d^2 (pi-pe)g]/18η Where, d is the diameter of the particles dx/dt is the rate of settling, ρi is the density of the particle, ρs is the density of the medium, g is the gravitational constant, and Ƞ is the viscosity of the medium

Small scale (Community pharmacy) >Extemporaneous techniques __________ involves reduction of size by rubbing particles in a mortar and pestle

Trituration

Particle Size of Powders: U.S. Pharmacopeia (USP) terminology for powders: ________ is the USP terminology when all particles of a powder pass through a No. 8 sieve and not more than 20% through a No. 60 sieve

Very Coarse (No. 8)

Particle Size of Powders: U.S. Pharmacopeia (USP) terminology for powders: ________ is the USP terminology when all particles of a powder pass through a No. 80 sieve. There is no limit to grater fineness

Very fine (or a No. 80)

Hard Gelatin Capsules: ______ of the gelatin solutions is vital to the control of the thickness of the cast film

Viscosity -viscosity is measured on a standard 6-23% w/w solution at 60 C in a capillary pipette and is generally in the range of 30-60 millipoise.

Which of the following are disadvantages of gelatin capsules? CHOOSE ALL THAT APPLY A. Filling equipment for capsules is slower than tableting. B. Hard gelatin capsule products tend to be more costly to produce than tablets. C. Highly soluble salts cannot be formulated. D. Risk of getting lodged in esophagus where the resulting localized high concentration of certain drugs (e.g.., doxycycline, potassium chloride, indomethacin) may cause damage.

all of them

Particle Size of Powders: Particle Size of powders influence a variety of important factors: 3. SUSPENDABILITY of particles that are intended to remain undissolved but uniformly dispersed in a liquid vehicle (e.g. fine dispersions have particles approximately 0.5-10 micrometers) When particle size is reduced, suspendability is _______(increased or reduced?)

increased

Particle Size of Powders: Particle Size of powders influence a variety of important factors: 1. Dissolution rate: A REDUCTION in particle size (micronization) _______(increases or decreases?) the rate of drug dissolution and its bioavailability

increases the rate of drug dissolution

Particle Size Distribution of Powders -a particle population which consists of spheres or equivalent spheres of the same diameter is said to be ________ or _________

monosized or monodisperse -however, monodisperse powders are rarely observed and most pharmaceutical powders contain particles of various diameters

Modern Techniques: The Lyophillization (freeze drying) process is MOST commonly used in formulated _________

parenterals (e.g. antibiotics, proteins, vaccines, etc. which are unstable in solutions)

Micromeritics: the science of small particles -important in pharmacy because powders form the basis of dosage forms like tablets, capsules, etc. The SIZE and SHAPE of particles affect: 1. Physical stability 2. Pharmacologic response The control of particle ______ is essential in achieving necessary flow properties and mixing, and in the release of drugs from dosage forms

particle size

Soft Gelatin Capsules or Soft Elastic Capsules: Soften gelatin capsules are often abbreviated as 'SOFTGELS': A softgel capsule shell consists of gelatin, water, and a _______

plasticizer -plasticizers make softgel shell elastic and pliable. They account for 20-30% of formulation

Small scale (Community pharmacy) >Extemporaneous techniques _______ involves the use of an additional material for reducing size of gummy substances or substance which tend to reagglomorate or that resist grinding

pulverization by intervention -for example, camphor cannot be pulverized by trituration b/c of its gummy nature, a small amount of alcohol or a volatile solvent will be added -similarly, iodine crystals may be comminuted by aid of ether

Characterization of Powder Flow: Indirect Methods: There is an empirical relationship between ANGLE OF REPOSE and flowability of powder -easily determined by allowing a powder to flow through a funnel and fall freely onto a surface -the height and diameter of the resulting cone are measures and the angle of repose is calculated What is the equation to calculate the angle of repose?

tan∅= height of the powder cone (h)/radius of the powder cone (r)

Particle Size of Powders: Particle Size of powders influence a variety of important factors: 2. __________ ensures dose-to-dose content uniformity (consistency)

uniform distribution

Uneven powder flow can cause _________ and ______&________

weight variation -as granules of various sizes will be formed capping & lamination--due to excess of entrapped air

Which of the following are advantages of gelatin capsules over tablets? CHOOSE ALL THAT APPLY A. better bioavailability than tablets--gelatin shells dissolve rapidly and release drug rapidly B. ease of formulation since powder compatibility is not required C. diverse systems can be filled--beads, granules, small tablets, powders, and even semisolids D. modified-release beads are intact because compression is not involved with gelatin capsules

all of them are advantages of gelatin capsules -also are good for blinding dosage for identity in clinical trials

Hard Gelatin Capsules: _________ is an important property which is a measure of gel rigidity. It is defined as the load in grams required to push a standard plunger 4 mm into the gel

Bloom strength

Describe the 4 factors that affect powder flow

1. Particle size -fine particles are more cohesive than coarser particles -Particles > 250 µm are free flowing where as < 100 µm are cohesive. 2. Particle shape: -Particle shape influences the interparticulate contact areas and thus flowability. -Spheres has minimum interparticulate contact and thus have good flowability. -Whereas, particle flakes or irregular shaped particles have very high surface-to-volume ratio and poorer flow properties. 3. Particle density: -Powder flow normally is influenced by gravity. -Thus, powders with particles of higher density have better flowability. 4. Surface texture: -The presence of electrostatic forces can increase interparticulate attractions and promote closer packing, resulting in increased cohesion and poor flow.

Special Problems in Dispensing Powders: Hygroscopic and Deliquescent powders: Problem: Hygroscopic powders will absorb moisture form air and deliquescent powders absorb moisture to the extent that they partially or wholly liquefy. Examples: phenobarbital sodium physostigmine hydrobromide, zinc chloride Describe two techniques that help prevent hygroscopic and deliquescent powders from absorbing moisture

1. dispense the ingredients in a tight container and incorporate dessicant 2. sometimes can be diluted with inert drying powder to reduce surface area exposed to moisture

Name two factors that influence particle size distribution

1. particle shape 2. particle size reduction -also an important factor that influences size distribution. For example, uneven milling can result in particles with various sizes and leads to a change in the size distribution

Special Problems in Dispensing Powders: What are two techniques used to prevent efflorescent powders from becoming sticky/pasty or liquefying?

1. use anhydrous salt form of the drug 2. include a drying bulky diluent with light, noncompacting method of mixing powders

Calculations: -Constitution of dry powders for oral use: The label for a dry powder package of cefprozil (CEFZIL) for oral suspension directs the pharmacist to add 72 mL of purified water to prepare 100 mL of suspension. If the package contains 2.5 g of cefprozil, how many milligrams of the drug would be contained in each teaspoonful dose of the constituted suspension?

2.5 g of cefprozil = 2500 mg, so we have 2500 mg of cefprozil in 100 mL of suspension 1 mL of suspension x (2500 mg cefprozil/100mL) =25 mg of cefprozil, so there is 25 mg cefprozil in 1 mL 1 teaspoonful= 5 mL, so (25 mg/1mL) x 5 mL = 125 mg Cefprozil Answer: 125 mg Cefprozil

Characterization of Powder Flow: Indirect Methods: An oral antibiotic powder when allowed to flow through a funnel results in formation of a cone with a height of 12 cm and a radius of 6 cm. The angle of repose of oral antibiotic powder will be: A. 63.43° B. 26.56° C. 45° D. 90°

A. 63.43° tan∅= height of the powder cone (h)/radius of the powder cone (r) Given: h=12 cm r=6 cm Solve: tan∅= 12 cm/6 cm tan∅= 2 cm Take the inverse tangent of 2 cm to find the angle of repose: tan^-1(2)=63.43°

Particle Size Analysis: Which particle size analysis technique determines particle size by the reduction in light reaching the sensor as particle is dispersed in a liquid or gas passing through a sensing zone (range 0.2-500 micrometers)? A. Light energy diffraction or dynamic light scattering B. Laser holography C. Cascade impaction

A. Light energy diffraction or dynamic light scattering

The flowability of a powder is of critical importance in the production of dosage forms. A. True B. False

A. True

The gelatin used in hard capsules is of a higher bloom strength (200-250g) than that used for soft capsules (150g) b/c a more rigid film is required for the manufacturing process. A. True B. False

A. True

Solid powders are chemically more stable than liquids. A. True B. False

A. True -for example, the shelf life of powders for antibiotic suspensions is 2-3 years, but once they are reconstituted with water, it is 2-3 weeks

Which of the following excipients is added to capsule powder as a filler or diluent? A. lactose B. croscarmellose C. magnesium stearate D. sodium lauryl sulfate

A. lactose -also starch and microcrystalline cellulose

Which of the following excipients is added to assist breakup and distribution of the capsule's contents A. lactose B. croscarmellose C. magnesium stearate D. sodium lauryl sulfate

B. Croscarmellose -is a disintegrant -also sodium starch glycolate and pregelatinized starch.

Hard Gelatin Capsules--Sizes and Shapes: Tampering with capsules is a safety concern. To avoid tampering, sealing and self-locking closures were developed. Hard gelatin capsules may be hermetically sealed by "banding", which involves layering down a film of gelatin around the seam of the cap and body (see image). Which of the following is an example of this safety technology? A. Pulvules B. Kapseals C. Spansules D. Coni-Snap capsules

B. Kapseals

Particle Size Analysis: Which particle size analysis technique determines particle size by firing a pulsed laser through an aerosolized particle spray and is photographed in three dimensions with a camera? A. Light energy diffraction or dynamic light scattering B. Laser holography C. Cascade impaction

B. Laser holography

Carr's compressibility index is used to determine which of the following? A. particle shape in powders B. flowability of powders C. particle density in powders D. particle size in powders

B. flowability of powders

All of the following are true regarding powder flow EXCEPT: A. fine particles are more cohesive than coarser particles B. powders with particles of lower density have better flowability C. the greater the presence of interparticulate attractive forces, the poorer the flow D. irregular shaped particles that have very high surface-to-volume ratio have poorer flow properties

B. powders with particles of lower density have better flowability Correction: Powders with particles of HIGHER density have better flowability

Calculations: -Constitution of dry powders for Parenteral use: The package information enclosed with a vial containing 5,000,000 units of penicillin G potassium (buffered) specifies that when 23 mL of a sterile solvent are added to the dry powder, the resulting concentration is 200,000 units/mL. On the basis of this information, how many milliliters of sterile water for injection should be used in preparing the following solution? Rx : -Penicillin G Potassium (buffered):5,000,000 units -Sterile Water for Injection q.s. -Make solution containing 500,000 units per mL -Sig. One mL = 500,000 units of Penicillin G Potassium

From package information, the volume of dry powder = 25-23 mL = 2 mL The final volume of prescription = 5,000,000 / 500,000= 10 mL Therefore, we need to add 10 mL - 2 mL (volume of dry powder) = 8 mL of sterile water for injection

Capsule shells are usually made of _______. However, they may also be made from starch, HPMC, or other suitable substances

Gelatin

Formulation (review): 1. Diluent or filler >>Lactose, microcrystalline cellulose, and starch. 2. Disintegrants - assist breakup and distribution of the capsule's contents >>Croscarmellose, sodium starch glycolate and pregelatinized starch. 3. Lubricant - For free flowing of powder mix or granules >>Magnesium stearate. 4. Wetting agents >>Surfactants such as sodium lauryl sulfate are added at 1% concentration to improve wetting of hydrophobic powder mixture. >>. Surfactants lower the advancing contact angle, aids in displacing and air phase at the surface, and replaces it with liquid phase (Gastric fluid).

Inserting tablets or small capsules into capsules is sometimes useful to separate chemically incompatible agents . Some non-aqueous liquids such as fixed or volatile oils can be filled in capsules. Capsules are cleaned and polished after filling to remove any powder that is adhering on capsules.

_________ are finely divided powders for administration to ear, nose, or throat. A __________ is employed too administer these products

Insufflations; insufflator (powder blower)

Small scale (Community pharmacy) >Extemporaneous techniques ______ involves the reduction of particle size by first forming a paste by the addition of a suitable nonsolvent to solid material, and then rubbing the paste in a mortar with a pestle or on an ointment slab using a spatula

Levigation -mainly used to incorporate solids into dermatological and ophthalmic ointments and suspensions Note: mineral oil and glycerin are commonly used levigating agents

Modern Techniques: The ________ process of particle reduction involves freezing the drug in aqueous solution or suspension (-40 C), followed by reducing the pressure (<4.57mm Hg) and removing the water by sublimation. An overall liquid-to-vapor transition takes place

Lyophillization (freeze drying) -the product is light and porous and will be solubilized readily when reconstituted Stages of freeze drying process: -freezing stage -vacuum application state -sublimation stage -secondary drying

Soft Gelatin Capsules or Soft Elastic Capsules: -softgel capsules have preservatives methyl paraben and/or propyl paraben -softgels can be oral softgels, chewable softgels, suckable softgels, twist-off softgels, and meltable softgels (pessaries or suppositories)

Manufacture of Softgels (see image)

_______ is the science of small particles

Micromeritics