Assignment 4:

1. Define tablets. Tablets are solid oral dosage forms commonly prepared with the aid of pharmaceutical
ingredients. These are one of the most popular dosage forms because it its convenience in administration and
manufacturing. These may have distinctive characteristics such as in shape, sizes, solubilities.

2. Differentiate the following tablets:

A. Compressed tablets – These tablets are prepared by means of compressive force on powdered, crystalline,
or granular substances into the required geometry by the application of high pressures and utilizing steel
punches and dies. These are designed to provide rapid release of the drug and systemic absorption of the
dosage form.
         
B. Multiple Compressed Tablets – These are produced when two or more incompatible components are
involved with the same tablet. These tablets are prepared by subjecting the fill material to more than one
compression.

C. Sugar Coated Tablets – These are compressed tablets that have been coated with a sugar syrup layer to
enhance patient compliance, increase esthetic appeal, mask objectionable tastes or smells, increase consistency
and/or adjust the release of a therapeutic agents.
         
D. Film-Coated Tablets – These tablets have a thin layer of polymer capable of producing a skin-like film
which is typically colored and has the advantage over the sugar coatings because it is more durable, less time-
consuming to add.

E. Enteric-Coated Tablets – These tablets have delayed release capacity because these are intended to pass
unchanged through the stomach to the intestines, where the tablets disintegrate and cause the medication to
dissolve and absorb and/or have an effect.
         
F. Gelatin-Coated Tablets – These tablets are coated with either one or two shades of gelatin color. These
have the same general characteristics as sugar coating and film coating with the added benefit of enhancing the
stability of photosensitive APIs. These tablets are suitable for double-blind clinical trials or for medications
that may irritate the esophageal mucosa when integrated into an immediate-release pill.

G. Buccal tablet – These are tablets that dissolve when it is between the cheek and gum allowing the direct
absorption of the active ingredient through the oral mucosa.
                 
H. Sublingual tablet – These are tablets that are dissolved under tongue to be fully absorbed into the blood
through the tissue there.
    
I. Chewable tablet - These are large tablets that are difficult to ingest so they are chewed in the buccal cavity
prior to swallowing. These tablets are useful for the delivery of large tablets to children and adults who have
trouble swallowing traditional solid dosage forms or antacid formulations.
              
J. Effervescent tablet – These are uncoated tablets formulated by compressing granular effervescent salts
which release gas when in contact with water. These tablets typically involve organic acids, and sodium
bicarbonate in combination with the active ingredients.

K. Instant Disintegrating – These are tablets that dissolve instantaneously releasing the drug within a few
seconds without the need of water, when put on tongue.

L. Vaginal tablet – These tablets are also called as vaginal inserts. These are uncoated, bullet-shaped, or ovoid
tablets inserted into the vagina for local effects. These usually contain antibacterial used for treatments.
M. Molded Tablets – These are tablets made from mixtures of active pharmaceutical compounds and a diluent
typically consisting of lactose and powdered sucrose in differing amounts. These are very friable, and care
must be taken in packing and dispensing.

N. Tablet Triturate – These are thin, typically cylindrical shaped or compact tablets that contain minute
quantities of usually potent drugs. Small amount of pressure is exerted during the manufacturing of these
tablets because these are fully soluble in water. These are used for compounding because these can be
incorporated into capsules or dissolved in liquid in order to have a precise dose of potent drugs.

O. Hypodermic Tablets – These are soft, conveniently soluble tablets that are initially used for preparation of
parenteral solutions. These are also convenient because these can be kept in the medical bag of the physician
and the injections prepared to mee the needs of a specific patients.

P. Dispensing Tablets – These are no longer in use tablets. These are termed as compounding tablets because
these contains large amounts of highly potent drug substances. These kinds of tablets have the dangerous
potential of being inadvertently dispensed as such to patient.

Q. Immediate Release Tablets - These are tablets designed to disintegrate and release their medication with
no special rate-controlling features, such as special coatings and other techniques

R. Extended-Release Tablets – There are tablets that are sometimes called controlled-release tablets. These
are designed to release their medication in a predetermined manner over an extended period.
               

3. Give the compendial requirements or quality standards for the following:

a) tablet weight variation – Adjustment into the volume of fill is done to the first few tablets inorder to yield
the desired weight and content. For example, if a tablet is to contain 20mg of a drug substance and if 100,000
tablets are to be produced, 2000 g of drug is included in the formula.
b) content uniformity – The requirements for content uniformity are met if the amount of active ingredient in
each dosage unit lies within the range of 85% to 115% of the label claim and the standard deviation is less than
6%.
c) table thickness - In order to achieve uniformity of tablets during production, care must be observed to
ensure the same factors of fill, die and pressure.
d) tablet hardness – Tablets should be sufficiently hard to resist breaking during normal handling and yet soft
enough to disintegrate properly after swallowing.
e) tablet disintegration – The tablets must first disintegrate and discharge the drug to the body fluids for
dissolution to become fully available for absorption.
d) table dissolution – Drug must be categorized according to the drug classification it belongs. Dissolution
classification: I – High solubility, high permeability; II – low solubility and high permeability; III – High
solubility and low permeability; IV – Low solubility and low permeability.

4. Name the factors determining table thickness. The factors in determining the tablet thickness are diameter
of the die, the compaction characteristics of the fill material and the force or pressure applied during
compression.

5. Name the apparatus to measure tablet thickness. In measuring the tablet thickness, a hand gauge or an
automated machine/equipment can be used.

6. What is friability and name the apparatus to test it. Friability describes the tendency of a solid substance
to break into smaller pieces. The tablet’s durability may be determined with the use of a friabilator.
7. What is IVIVC? Interpret each category? IVIVC stands for in vivo-in vitro correlation. With this system,
drugs are categorized into 4: I (high solubility and high permeability), II (low solubility and high
permeability), III (High solubility, low permeability) and IV (Low solubility, low permeability)

8. What are the factors affecting table disintegration and dissolution. The factors that can affect tablet
disintegration and dissolution are particle size of the drug substance, solubility and hygroscopicity of the
formulation, type and concentration of the disintegrant, binder and lubricant, manufacturing method,
particularly the compactness of the granulation and compression force used in tableting.

9. Give the name of the apparatus assembly for drug release and dissolution testing. USP Apparatus 1 and
USP Apparatus 2 are used for immediate-release solid oral dosage forms. These equipment consists of (1)
variable speed stirrer motor; (2) cylindrical stainless steel basket on a stirrer shaft [USP Apparatus 1] or a
paddle as the stirring element [USP Apparatus 2]; (3) a 1,000-mL vessel of glass or other inert transparent
material fitted with a cover having a center port for the shaft of the stirrer and three additional ports, two for
removal of samples and one for a thermometer; and (4) a water bath to maintain the temperature of the
dissolution medium in the vessel.

10. What is pooled dissolution testing? Pooled dissolution is a process that has emerged since dosage units
within a batch are generally not the problem. This recognizes batch characteristics and allows pooled
specimens to be tested.

11. Name the 3 methods of preparing compressed tablets. The 3 methods of preparing compressed tablets
are wet granulation, dry granulation and direct compression.

12. What property of granulation is important in making tablets? The free-flowing property of granulation
is important in making tablets. Having this kind of property makes it easy for the fine powders to be
compressed.

13. Enumerate the steps in order in wet granulation method. The steps involved in wet granulation method
are: weighing and blending, preparing the damp mass, screening the damp mass into pellets or granules, drying
the granulation, sizing the granulation by dry screening, and adding lubricant and blending.

14. Name 2 All-in One granulation method. The two methods under all-in-one granulation are the a) fluid
bred process which uses a single piece of equipment call the fluid bed granulator, and the b) microwave
vacuum processing, which allows the powders to be mixed, wetted, agglomerated and dried within the
confines of a single piece of equipment.

15. Describe the mechanical process of a single punch operation of making tablets. As the lower punch
drops, the feed shoe filled with granulation from the hopper is positioned over and fills the die cavity. The feed shoe
retracts, scrapes away the excessive granulation, and levels the fill in the die cavity. The upper punch lowers and
compresses the fill, forming the tablet. The upper punch retracts as the lower punch rises with the formed tablet to
the precise level of the stage. The feed shoe moves over the die cavity, shoves the tablet aside, and once again fills
the cavity with granulation to repeat the process. The tablets fall into a collection container. Samples of tablets are
assayed and tested for the various quality standards described earlier.

16. What problems on tablets can be encountered during its high-speed production? During high-speed
production, the following problems may be encountered:
 Increased occurrence of lamination (horizontal striations)
 Tablet capping in which separation of the top of the tablet from the whole happens because fill
material does not have enough time to bond after compression.

17. What conditions would make materials applicable for dry granulation? In order for the materials to
proceed with dry granulation, the materials that cannot be prepared by wet granulation because they degrade in
moisture or the elevated temperatures required for drying the granules. The active ingredient or the diluent
must also have a cohesive property.

18. How do dry granulation of tablets be accomplished? In order to accomplish the dry granulation of
tablets, the powder mixture is slugged or compressed into large flat tablets or pellets. The slugs are broken up
by hand or by a mill and pass through a screen of desired mesh for sizing. Also, roller compaction with the use
of powder compactors may also be used in increasing the density of a powder by pressing it between rollers at
1 to 6 tons of pressure. This method is preferred to slugging.

19. Give three reasons for tablet coating.

Tablet are coated for some reasons:
 Protect medicinal agent against destructive exposure to air and/or humidity
 To mask the taste of the drug
 To provide special characteristics of drug release

20. Enumerate the steps in sugar coating.

The steps in sugar coating are the following:
 Waterproofing and sealing coats
 Subcoating
 Smoothing and Final Rounding
 Finishing and coloring
 Imprinting
 Polishing

21. Name 3 ways of imprinting logos/ID on tablets. Imprinting on tablets may be debossed, embossed or
engraved. Debossed means imprinted with a mark below the surface. Embossed mean the mark is raised
above the surface. Engraved means there is a cut into the surface during production.

22. What are the materials found in a non-aqueous film-coating solution? A non-aqueous film-coating
solution contains:
 Film Former – produces smooth thin films reproducible under conventional coating conditions and
applicable to a variety of tablet shapes.
 Alloying substance – provides water solubility to the film
 Plasticizer – provides flexibility and elasticity to the coating.
 Surfactant – enhances the spreadability of the film
 Opaquants and colorants - makes the tablet’s appearance appealing and distinctive
 Sweeteners, flavors and aromas – enhance the acceptability of the tablet
 Glossant – provides lister to the tablet without the use of a separate polishing operation.
23. What is the most important factor to consider for enteric coated tables? The most important factor to
consider in enteric coated is based on factors of pH, which resists dissolution in the highly acid environment of
the stomach but yielding to the less acid environment of the stomach but yielding to the less acid environment
of the intestine.

24. Name 2 ways how coating is applied to tablets. For the waterproofing and sealing coats, it is done by
gently pouring the waterproofing solution or sprayed on the compressed tablets then warm air is blown into the
pan during the process of coating for drying and to prevent the sticking of the tablets all together. Next is the
subcoating where in , 3-5 subcoats of a sugar-based syrup are applied to bond the sugar coating tablet and
provide rounding .

25. What are the 3 types of fluidized bed systems and when is each system applicable?
The 3 types of fluidized bed systems are Wurster process, top-spray method, and the tangential spray
technique. In Wurster process, items to be coated are fed into a vertical cylinder and are supported by a
column of air that enters from the bottom of the cylinder. This process is used for sustained-release and enteric
release products. The top-spray method where in the coating solution is sprayed downward onto the particles
to be coated as they are suspended by air from below. This method is recommended for taste making, enteric
release and barrier films on tablets. The tangential spray method is a technique used in rotary fluid bed
coaters. This method is recommended for layering coatings and for sustained-release and enteric coated
products.
26. How can the quality and performance of a solid dosage form be altered? The quality and performance
of a solid dosage form can be altered by modifying the formulation or changes during manufacturing.

Formulation changes may be affected by:

a) use of starting raw materials (both active ingredient and pharmaceutical excipients that differ in
chemical or physical characteristics)
b) use of different pharmaceutical excipients
c) use of different quantities of the same excipients in a formulation
d) addition of a new excipient to a formulation.

Manufacturing changes may rise from:

(a) use of processing or manufacturing equipment of a different design
(b) a change in the steps or order in the process or method of manufacture
(c) different in-process controls, quality test, or assay methods
(d) production of different batch sizes
(e) employment of different product reprocessing procedures
(f) employment of a different manufacturing site.

27. Name some precautions in packaging and storing volatile drugs. Volatile drugs must be preserved in
tight containers preferably glass and then stored at a controlled room temperature to be able to maintain the
potency of the tablets.

Assignment 5
Modified release Dosage form
 
1. What are modified release dosage forms? Modified release dosage forms are used to describe dosage
forms having time, course and location as basis if drug release features.

2. Differentiate the following dosage forms:

 extended-release – defined as an extended-release dosage form as one that allows a reduction in
dosing frequency from that necessitated by a conventional dosage form, such as a solution or an
immediate-release dosage form.
 delayed-release – dosage form designed to release the drug at a time other than promptly after
administration.
 repeat action – dosage form that is designed to contain 2 single dose of medication, one for
immediate release and the second for delayed release.
 targeted release – dosage form where drug release directed toward isolating or concentrating a drug
in a body region, tissue, or site for absorption or for drug action.
3. What are the advantages of extended release dosage forms over conventional forms? Name
some disadvantages.
The following are the advantages of extended-release dosage forms over conventional forms:
 less fluctuation in drug blood levels
 frequency reduction in dosing
 enhanced convenience and compliance
  reduction in adverse side effects
 reduction in overall health care costs
In the other hand, the following are the disadvantages of extended-release dosage forms:
 loss of flexibility in adjusting the drug dose and/or dosage regimen
 a risk of sudden and total drug release or dose dumping, due to a failure of technology

4. What are the characteristics of drugs best suited for incorporation into an extended release
product? The following are the characteristics of drugs best suited for incorporation into an extended-release
product:
 They exhibit neither very slow nor very fast rates of absorption and excretion.
 They are uniformly absorbed from the gastrointestinal tract.
 They are administered in relatively small doses.
 They possess a good margin of safety.

5. Give the mechanisms by which extended drug action are achieved. Extended drug action is achieved by
affecting the rate at which the drug is released from the dosage form and/or by slowing the transit time of the
dosage form through the gastrointestinal tract for orally administered dosage forms.

6. Explain 3 ways by which the rate of drug release from the solid dosage forms be modified. The rate of
drug release from the solid dosage forms can be modified by the technologies based on the following:
 Modifying drug dissolution by controlling access of biologic fluids to the drug through the use of
barrier coatings
 Controlling drug diffusion rates from dosage forms
 Chemical reaction or its pharmaceutical barrier and site-specific biologic fluids

7. Explain the different technologies employed in the modification of drug release rate. Give the
products employing these modifications.
a) coated beads, pellets, granules, microspheres – system where in the drug is distributed onto beads,
pellets, granules or other particulate systems.
b) multitablet system – System where in small spheroid compressed tablets 3 to 4 mm in diameter may be
prepared to have varying drug-release characteristics
c) microencapsulated drugs – System where in microencapsulation takes place by which solids, liquids or
even gases may be enclosed in microscopic particles by formation of thin coatings of wall material around the
substance.
d) embedding drug in slowly eroding/hydrophilic matrix system – System where in the drug substance is
combined and made into granules with an excipient material that slowly erodes in body fluids, progressively
releasing the drug for absorption.
e) embedding drug in inert plastic matrix – System where in the drug is granulated using an inert plastic
material. Drug is slowly released from the inert plastic matric by diffusion.
f) complex formation -
g) ion-exchange resins – System where in a solution of a cationic drug may be passed through a column
containing an ion-exchange resin, forming a complex by the replacement of hydrogen atoms.
h) osmotic pump – System that composes of a core tablet surrounded by a semipermeable membrane coating
having a 0.4mm diameter hole produced by laser beam.

8. What are the reasons why drugs must remain intact until it reaches the intestines? How are
these be achieved? Drugs must remain intact until it reaches the intestines to protect by gastric fluids, to
reduce gastric distress from happening that is caused by drugs particularly irritating to the stomach, or to
facilitate gastrointestinal transit for drugs that are better absorbed from the intestines.

9. How would you develop an IVIVC model? To develop an IVIVC model, the following must be done:
  Develop formulations with different release rates or a single-release rate if dissolution is independent
of condition
 Obtain in vitro dissolution profiles and in vivo plasma concentration profiles for these formulations
 Estimate the in vivo absorption or dissolution time course for each formulation and subject using
appropriate mathematical approaches.

10. What are the clinical considerations in the use of oral modified-release dosage forms?
The following are the clinical considerations in using oral modified-release dosage forms:
 Patients should be advised of the dose and dosing frequency of modified drug-release products and
instructed not to use them interchangeably or concomitantly with immediate-release forms of the same
drug.
 Patients stabilized on a modified-release product should not be changed to an immediate-release
product without giving consideration of the blood level concentration.
 Patients should be changed to another extended-release product unless there is assurance of equivalent
bioavailability
 Patients should be advised that modified-release tablets and capsules should not be crushed or chewed
 Patients fed through enteral nutrition through nasogastric tube may receive conventional or modified-
release medication.
 Modified-release tablets and capsules should not be used as the source of a drug to prepare other
dosage forms such as pediatric oral liquids
 Patients and caregivers should be advised that nonerodable plastic matric shells and osmotic tablets
remain intact throughout gastrointestinal transit and the empty shells or ghosts from osmotic tablets
may be seen in the stool
 Patients must be assured of normalcy of this event and that drug absorption has taken place.

11. How can extended drug action be achieved by routes other than oral administration?
Extended drug action can be achieved by parenteral administration which includes the use of crystal or
amorphous drug forms having prolonged dissolution characteristics, slowly dissolving chemical complexes of
the drug entity, solutions, or suspensions of drug in slowly absorbed carriers. The rate and duration of drug
delivery may also be controlled mechanically with the use of controlled-rate drug infusion pumps.