Bioadhesion can be defined as a phenomenon of interfacial molecular attractive forces in the

midst of the surfaces of the biological substrate and the natural or synthetic polymers, which
allows the polymer to adhere to the biological surface for an extended period of time.
Bioadhesive polymeric systems have been used since extent in the development of products for
various biomedical applications which include denture adhesives and surgical glue. Considerable
attention has been focused in recent years on the delivery of drugs through the oral mucosa
which have a high first pass metabolism or degrade in the gastrointestinal tract. Buccal delivery
involves the administration of the desired drug through the buccal mucosal membrane lining of
the oral cavity. Unlike oral drug delivery, which presents a hostile environment for drugs,
especially proteins and polypeptides, due to acid hydrolysis and the hepatic first-pass effect, the
mucosal lining of buccal tissues provides a much milder environment for drug absorption.
Mucoadhesive controlled-release devices can improve the effectiveness of a drug by maintaining
the drug concentration between the effective and toxic levels, inhibiting the dilution of the drug
in the body fluids, and allowing targeting and localization of a drug at a specific site.
Mucoadhesive characteristics are a factor of both the bioadhesive polymer and the medium in
which the polymer will reside. Buccal dosage forms can be of Matrix or Reservoir types.
However, this route could become a significant means for the delivery of a range of active agents
in the coming years, if the barriers to buccal drug delivery are overcome.

Amongst the various routes of drug delivery, oral route is the most preferred to the
patient. However, disadvantages such as hepatic first pass metabolism and enzymatic
degradation within the GI tract limits its use for certain drugs. Different absorptive
mucosa are considered as potential site for drug administration.  e.g. nasal, rectal,
vaginal, ocular and oral cavity  Noninvasive systemic administration.  Local targeting /
systemic drug delivery

These drug delivery system utilize property of bioadhesion of certain water soluble
polymers which become adhesive on hydration and hence can be used for targeting
particular site. Buccal delivery is the administration of the drug via buccal mucosa
(lining of the cheek) to the systemic circulation.

Concepts of Buccal Drug Delivery System

Mucoadhesive  polymers as drug delivery vehicles. The common principle underlying

this drug administration route is the adhesion of the dosage form to the mucous layer
until the polymer dissolves or the mucin replaces itself. Benefits for this route of drug
administration are: prolonged drug delivery, targeted therapy and often improved
bioavailability.

Bioadhesion and Mucoadhesion

Bioadhesion is the state in which two materials, (at least one of which is  biological in
nature), are held together for a extended period of time by interfacial forces. The term
bioadhesion implies attachment of drug-carrier system to specific biological location.
This  biological surface can be epithelial tissue or the mucous coat on the surface of
tissue.

If adhesive attachment is to mucous coat then phenomenon is referred as

mucoadhesion. Mucoadhesion is defined as the interaction between a mucin surface
and a synthetic or natural polymer. Mucoadhesion can also be explained on the basis
of molecular interactions composed of attractive    (Vander Waal’s, Hydrogen bonding)
and repulsive forces (Electrostatic, steric). For mucoadhesion to occur, the attractive
interaction should be more than repulsive forces.

Biological membrane- the membrane of internal tract e.g.-GIT, buccal cavity, eye, nose
,vagina ,rectum are covered with a thick gel like structure know as mucin. All biological
formulation interact with mucin layer during process of attachement , it act as a link
between the adhesive and the membrane.

Mucous is a network of mucin glycoprotein that form a continuous layer that intimately
cover the internal tract of body. Total weight of mucous secreted by globlet cell only
contain less then 5% of glycoprotein. There are about 160-200 oligosaccharides side
chain in the glycosylated region of the glycoprotein. Each oligosaccharides unit have 8-
10 monosaccharides and terminal end of either sialic acid and L-fucose. Mucin have
network of negative charge due to sialic acid , sulfate residue

Mechanism of Bioadhesion

The bioadhesion mainly depends upon nature of bioadhesive polymer. First stage

involves an intimate contact between a bioadhesive & a membrane. Second stage
involves penetration of the bioadhesive into tissue. At physiological pH the mucous
network may carry negative charge because of presence of sialic acid & sulfate residue
and this high charge density due to negative charge contributes significantly to
bioadhesion.

Matrix tablets

Now a days as very few drugs are coming out of research and development and already existing drugs are suffering
the problem of resistance due to their irrational use specifically in case of drugs like antibiotics. Hence, change in the
 operation is a suitable and optimized way to make the some drug more effective by slight alteration in the drug
delivery. An appropriately designed controlled release drug delivery system can be a major advance towards solving
problems concerning the targeting of a drug to a specific organ or tissue and controlling the rate of drug delivery to
the target sites. The development of oral controlled release systems has been a challenge to formulation scientists
due to their inability to restrain and localize the system at targeted areas of the gastrointestinal tract. Matrix type drug
delivery systems are an interesting and promising option when developing an oral controlled release system. This
review focuses on the progress made in the design of controlled release dosage forms employing various types of
matrices as carriers for the active ingredients

its the type of tablet which is designed such that it releases it contents regarding first order kineticks or
zero order kinetics due to special arrangement and combination of hydrophobic and hydrophilic
polymers as an excipient to form a matrix. example of such a matrix tablets are, controlled release
tablet, sustained released tablet. these all come under the category of modified release tablet.

Sustained and controlled release

a) Prolonged release DDS

After a single dose the drug is released slowly and rate of absorption is slow. Onset
of action is delayed. Duration of action is greater than a conventional dosage form.
(b) Sustained release DDS
<!--[if !supportLists]-->        <!--[endif]--> <!--[if !vml]--><!--[endif]-->Contains loading dose
+ maintenance dose.
<!--[if !supportLists]-->        <!--[endif]-->Loading dose is immediately released to produce
quick onset of action.

 Sustained release, sustained action, prolonged action, controlled release, extended action,
timed release, depot, and repository (storage area) dosage forms

are terms used to identify drug delivery systems that are designed to achieve a prolonged therapeutic
effect by continuously releasing therapeutic agents over an extended period of time after
administration of a single dose.

 Avoid problems of drugs have a narrow therapeutic index ( small difference between toxic
level and therapeutic level)

• Requires multiple injections

• Poor patient compliance

• Increased incidence of infection and hemorrhages

 Avoid danger of systemic toxicity with more potent drugs.

  Improves availability of drugs with short half lives in vivo

• Some peptides have half-lives of a few minutes or even seconds

Liquisolid compacts

The concept of liquisolid tablets was developed from powdered solution technology
that can be used to formulate liquid medication 11. A liquisolid system is defined as
dry, non-adherent, free-flowing and compressible powder mixtures converted from
liquid drugs, drug suspensions or drug solutions in nonvolatile solvents with
selected carriers and coating materials12. In this technique, the drug is dissolved in a
non-volatile liquid and converted to dry, free flowing and compressible solid using
carrier and coat materials10. Since non-volatile solvents are used to prepare the drug
solution/suspension, the liquid is not evaporated and the drug is carried in a liquid
system and is dispersed throughout the final product.

Bilayered tablets:

Bilayer tablet is the novel technology for the development of controlled release formulation.
Developing a combination of two or more active pharmaceutical ingredients in a single
dosage form is known as a bilayer tablet. Now a days the use of bilayered tablets has been
increased. Bilayer tablet is more suitable for gradual release of two active ingredients in
combination. Bilayered tablet technology helps in separating the two incompatible
substances in which one layer is immediate release as loading dose and second layer is
controlled/sustained release as maintenance dose. Two incompatible drugs can also be
formulated into a bilayer tablet by adding an inert intermediate layer.
Define patient compliance.   The degree to which patient correctly follows medical advice
1. More economical - can make large commercial batches
possible, and is also cheaper to manufacture
2. More stable- so longer shelf-life
List reasons why tablets are
3. Can be tailored to special needs (ie. controlled/modified
considered the most popular  
release tablets) - enteric coating, protection for stability
dosage form.
4. Lots of resources available - technology and equipment, man
power and expertise, raw material and packing material,
contract manufacturing facilities
1. Immediate Release (IR)
2. Orally Disintegrating/Dispersable Tablet (ODT)
List the five different types of
  3. Chewable
tablets.
4. Effervescent
5. Modified Release
In IR tablets, the drug is released quickly and completely in
Briefly define immediate release
  one shot. Must do multiple daily dosing!
tablet.
Examples: acetominophen, aspirin tablets, ibuprofen
 Tablet designed to disperse/disintegrate in the mouth or on
Briefly define ODT (orally tongue. Generally used for patients experiencing dysphasia 
 
disintegrating tablet) (speech disorder) and compliance is an issue.
Example: donepezil for Alzheimers
Tablet often for ease of administration - pediatric (tablets
Briefly define chewable tablets.   suitable for children and infants) and also for quicker
absorption.
Briefly define effervescent These tablets are dispersed in water before administration.
 
tablets. Often used for quick absorption and for ease of administration.
MR is designed to release medication in a predetermined
manner and/or over an extended period of time.
What is modified release, and
list some of the advantages of   The advantages include:
modified release. 1) avoids peaks and troughs
2) less dosing frequency
3) patient compliance is improved
Categories of MR can be sub-divided into:
1) controlled release
2) sustained release
3) delayed release

Controlled release - these tablets are designed with a built-in

Modified release can be mechanism where external conditions will not affect the tablet
subcategorized into three
 
different categories. What are Sustained release - prolonged release is generally not "zero
they and define them. order" and is often influenced by surrounding environment

Delayed release - tablet only will be released at a specific site

(e.g. duodenum, colon). These tablets will often be enteric
coated in order to avoid release in the stomach, since the
stomach is highly acidic which can cause degradation. GI
disturbance can also affect tablet if not enterically coated.
1) ER coated particles and beads
List the different types of 2) ER inert matrix
 
extended release tablets. 3) ER hydrophilic/eroding matrix
4) ER osmotic
Briefly describe the oral Tablet must be disintegrated into granules, then be converted to
absorption process from IR   fine particles through deaggregation. These particles can then
dosage. be dissolved into solution and be absorbed.
List the general components of a   1. The API (Drug) - the active pharmaceutical ingredient
typical tablet and briefly define 2. Diluent - "inert filler to provide the properties of flow,
them. Which of these necessary bulk, and compression properties to granules (e.g.
components are considered the lactose, microcrystalline cellulose, starch, dicalcium
most important? phosphate)
3. Binder - provides necessary adhesion of powders into
granules to allow flow (e.g starch, methyl cellulose, povidone)
 - can also act as disintegrants when wetted
4. Disintegrant - makes tablet mass into smaller particles
-also superintegrants - more powerful and are crosslinked
polymers 
5. Lubricant - reduces friction during compression. Generally
the LAST stop in tablet processing before compression. (e.g
magnesium stearate, stearic acid)
6. Glidant - improves flow property
7. Film Coating - for protection
8. Polishing Agent - for attractive look
9. Opacifying agent - for opaque property

Most important is #1-5

What are the two types of tablet 1. Single stroke (punch) (R&D)
 
press? 2. Rotary
There are multiple stations in the rotary tablet compression
cycle. Each station has a set of die, upper, and lower punch.
Briefly describe the parts and The steps are fill, compress, and eject. Filling involves the fill
important steps of the rotary   cam, weight-adjustment pull down cam, feed frame, and wipe
tablet compression cycle. off blade. Compression involves the pre-compression and
compression cycles. Ejection involves the upper and lower
cam, and ejector knob. 
1. Dispensing (which includes milling, sieving, and weighing).
2. Granulation (multiple types)
List the typical manufacturing
  3. Compression of tablets
process steps of tablets.
4. Film coating
5. Packaging
Uniformity of blend (granules)
and its flow property are very
important to ensure each tablet
  TRUE
in the batch are identical and
deliver the label claim. True or
False?
Granulation is a process that joins solid particles using a binder
or binding force.

What is granulation, and the Advantages:

 
advantages of granulation? 1) improves flow property- weight uniformity
2) enhances compressibility of the tablet
3) increases dispersibility and uniformity of API in the tablet
4) reduces dust in the workplace
What is the difference between
dry granulation (slugging) and
wet granulation?