Lecture 14
We are going to start with Tableting and Compaction. The tablet is one of the most famous solid
dosage forms and comes from the Latin word Compressi which indicates the mechanism by
which these tablets have been formulated. The major route of administration for tablets is the
oral route, however we can find tablets that can be administered into the eyes and this is called
the ocular route of administration. Obviously if we are administering the tablets into a small
surface area like the eye, then it will have a small size of tablets and are called as mini tablets.
You would feel that this is inconvenient to administer a tablet into the eye; however the tablet
will not go into dissolution and disintegration rather it will be transformed into a jellified mass
(turns into a gel) and it will be spread over the eye through the mechanical force of blinking.
This is a less common solid dosage form of tablet. Mainly the tablet’s design is intended to be
administered via the mouth (oral route of administration). Gastrointestinal tract.
In the gastro intestinal tract, the major absorption site is the intestine.
Tablets can be formulated from lyophilized products (resulting from freeze drying) or otherwise
they can melt them and mold them into a tablet. Broadly speaking there are two forms of the
tablet, one of them has went under certain unit operations including size enlargement
(granulation) then compression/compaction, or otherwise we have brought the powder (you can
do mixing/drying) but without size enlargement and they are called direct compressed tablet.
The tablet can be formulated into compaction through different unit operations that might
include size enlargement, however if size enlargement is not included then this tablet via
compaction has been produced by direct compression. In other words, we don’t need further unit
operation or processing in order to bring the material into this tablet thus direct compression,
therefore in this tablet the kind of excipients allow for formation of strong tablets without the
need of wet granulation or a solvent. This material that has resulted from direct compression
most likely is resulting from flowable material (granules enhance flow ability). Therefore
excipients that are used are freely flowable.
The direct compressed tablets are limited by the nature of the polymeric material and the drug we
are using. If they satisfy the requirements that they are freely flowable and can attach to each
other without the need of a solvent, and some of them can act as a binder on dry stage and we
can process them via direct compression without need of size enlargement or otherwise
granulation.
The second mode of the tablet that includes size enlargement and we called it a compressed
tablet or a tablet that has been compressed via granulation.
The tablets are convenient to be used and in terms of safety it is dependent on investigating the
chemical and physical stability of the material. for example if you have formulated a tablet and
solute migration has occurred causing mottling or spotting of the tablet then this is not going to
be indicated as stability rather it is referred to stability with respect to general solid dosage form.
Safety is with regards to the API if it is bio compatible with the cell, and the selection of the
material from the start is safe. They can enhance safety criteria by limiting direct contact of the
drugs.
Tablets are convenient, safe, stable, reproducible and cheap.
They have poor F, are irritators or may have instability in the GIT.
With respect to bioavailability, sometimes tablets suffer from poor bioavailability (Poor F).
Symbol F is the fraction of the concentration available; bioavailability.
Bioavailability; bio (target site); availability in that site in two aspects, the amount that has
reached that site and the extent and how long does it take to reach the target site and how long is
the material sustained in that level.
Whenever we are going to measure therapeutic response, we are going to detect the
concentration if it is within therapeutic window.
They refer to bioavailability as a fraction. Bioavailability refers to the amount of the material and
the rate that it takes in order to reach target site (bio site). During this journey the major route of
administration is the oral route. In the oral route, the risk the drug encounters is the acidic
environment of the stomach or the basic environment of the intestine, some enzymes may cause
metabolism for drug, either way there is a chance for this drug to be available after being
absorbed. Not the entire drug is going to reach to the target site.
They formulate the drug as an aqueous solution form, and they make it administrable in the veins
via the injection, this should represent the full concentration of the drug, because once it reaches
the blood there is a minimal risk for the degradation by metabolism (there is metabolism but the
rate of metabolism with the rate of systemic circulation which finishes in one minute is going to
be minimal) and this will be the reference standard, then you compare the concentration that is
going to be available via other routes of administration and this is going to give you the fraction
that is available.
Generally for tablets administered in oral route of administration there is a high risk to be
degraded and because of that they can suffer from poor bioavailability (poor F).
Quality Attributes of tablets:
1- Correct dose, elegant appearance
2- Controlled and reproducible manner of release
3- Biocompatible, sufficient mechanical strength (to have element appearance for
packaging)
4- Stability (chemical, physical, microbiologically)
5- Patient acceptance (formulation and packaging)
Controlled release can be in two pattern prolonged release or sustained release.
For pharmacopeia tests with respect to microbial growth and different sterile requirements for
the tablet; for microbial growth there is limited concern because there is a lower probability for
such growth unless coating has been performed with a sugar. Sugar can provide a good
environment for such growth because once it interacts with humidity, they will provide nutrients
and a water medium and can cause molding of tablet, therefore an investigation is made for how
susceptible this tablet is for microbial attack however this is a limited concern.
The most important test achieved in accordance to pharmacopeia is the dose content or the assay
for the API. The concentration of API should be in according to the labeled amount and
producible in the entire batch, same content. Dose uniformity, and with respect to this all the
tablets should have the same amount of the dose; reproducibility. We should also have weight
uniformity, the tablet as a whole should have a uniform weight and each one of them should have
the labeled dose.
There are phases of tableting process flow;
You have already started the tableting using the single press machine. The steps are divided in
general with filling which is accompanied with continuous mixing process, there are like wheels
that are rotating either co-rotating (enhancing mix ability), or counter rotating that can cause size
reduction.
In the tableting machine we have punches; upper punch or lower punch. A punch looks like a
nail, one on the upper part and the other on the lower part, the shape of the foot of punch is going
to determine shape of tablet, sometimes it has a slit or it can stamp the tablet.
The punch should hold the force of compression that is applied, and to be inert (made of stainless
steel). In the filling process, the powder starts to flow and the lower punch is attached to a ribbon
for inclination, for the cavity to be filled with powder. In accordance to desired thickness of
tablet I will lower this punch.
Filling is according to volume in this stage, if you are concerned about the mixing and thus non-
uniform weight filling, then there is a sensor that will tell you the weight.
Upper punch controls the force of compression and afterwards you will determine time of
pressing and deaattach. Lower punch determines thickness and acts as a stationary punch and the
upper punch enforces compression.
In single punch machine, it is important to consider weight uniformity, because there is a high
chance that the upper punch is going to have stickiness and thus remains of the powder that can
be loaded on the other powder and lost from a previous powder population
For the Rotatory press, each couples are interacting with each other (upper punch and lower
punch together), and thus the production rate is higher than single press (one tablet per time).
Then we have ejection, and the lower punch moves to return to its original place therefore we
have ejection of the tablet.
