METHODS OF FORMULATION

AND EVALUATION OF BDDS

PRESENTED TO:
DR.SATHEESHA BABU. B K
ASSOCIATE PROFFESOR
DEPT OF PHARMACEUTICS
GCP
CONTENTS:
• Types of formulation
• Evaluation of BDDS
METHODS OF FORMULATION
 Formulation of BDDS
The main components of BDDS:
• Drug substance
• Bio adhesive polymers
• Backing membrane
• Permeation enhancers
DRUG SUBSTANCE
The drug intended to be formulated should
satisfy following qualities:
• Molecular weight of the drug should be less than
1000da.
• Should be potent .
• Non-irritant to mucosa.
• Drugs that degrades in GIT can be given by buccal
route.
BIOADHESIVE POLYMERS :
 The term bio adhesion is commonly defined as
adhesion between two materials where at least one of
the material is of biological origin.
• When the adhesion is restricted to lining of the mucosal
layer, then it is known as muco adhesion.
TYPES:
1st generation polymers : PAA (poly acrylic acid),
NaCMC , HPMC, Carbapol , Chitosan , Xanthan gum, PVA
etc.

2nd generation polymers : Lectins , Thiolated polymers

etc
IDEAL CHARACTERISTICS OF
MUCOADHESIVE POLYMERS

 Non toxic, non irritable, free from leachable

impurities.
 Polymer pH should be biocompatible.
 Quick adherence, and sufficient mechanical strength.
 Acceptable shelf life.
 Optimum molecular weight.
 Easily available and cost should not be high.
• Backing membrane
• Backing membrane plays a major role in the
attachment of bioadhesive devices to the mucus
membrane.
The materials used as backing membrane should be
inert, and impermeable to the drug and penetration
enhancers.
Such impermeable membrane in buccal bioadhesive
patches/tablets prevents the drug loss and offers
better patient compliance.
The commonly used materials in backing membrane
include carbopol, HPMC, CMC etc.
Permeation enhancers
• Substances that help to promote drug permeation
through the buccal epithelium are referred to as
Penetration enhancers, Permeation promoters or
Absorption enhancers
• Ex: sodium Lauryl Sulphate, Sodium
glycodeoxycholate, sodiumglycocholate, caprylic
acid , lauricacid etc.
Factors affecting mucoadhesion in oral cavity
1.Polymer Related factor :
 Mol.Wt of polymer - MW increases, adhesion strength
increases. Ex :PEG-4000 and PEG-4,00,000.
 Flexibility – Mucoadhesion starts with the diffusion of
polymer flexibility ,it should be high in order to achieve
adhesion with mucus.
 Hydrogen –bonding Capacity – the desired polymers must
have functional groups that are able to form hydrogen bonds.
Ex : Poly(vinyl alcohol), Poly(methacrylic acid)
 Cross-linking density - Should be as low as possible.
Increasing density of cross-linking reduces the diffusion
of water into polymer network, which inturn causes
insufficient swelling of polymer and decreases adhesion.
 Charge - Charged polymers ( anionic and cationic) will
have high adhesion property compared to non-ionic
polymer.
 Concentration – If the conc. of polymer is too low ,the
number of penetrating polymer chains per unit volume of
mucus is small and interaction between polymer and
mucus is unstable. So more concentrated polymer gives
better adhesion.
2. Environmental factors:
The mucoadhesion of polymer not only depends on
the molecular properties, but also depends on the
environmental factors adjacent to the polymer like
 pH – The pH of saliva is 6.2-7.4,This can alter the
ionization state of polymer and therefore can affect the
adhesion of polymer.
 Mucin turn over rate – The residence time of
dosage forms is limited by the mucin turnover time,
which has been calculated to range between 47-
270min in rats and 12-24hrs in humans.
 Buccal tablets
 They are small, flat, oval/concave shape with 5-8mm
diameter.
 Direct Compression /Wet Granulation methods may
be used to formulate.
Tablets are directly placed onto mucosal surface & it
gets adhered to the surface.
Based on release – 2 Types
1) Unidirectional Release
2) Multi directional release (as with conventional
product)
• The tablets are prepared by mixing drug,
adhesive and additives and allowed for
direct compression.
Generally, for unidirectional release, a
backing membrane is applied to one side,
which is impermeable to liquid, so that no
drug release is observed from that side &
non-coated surface adheres to the Buccal
mucosa.
 Ethyl Cellulose is used as backing membrane.
 EX :Glyceryl trinitrate Buccal tab, Miconazole Buccal tab
 Evaluation of Buccal tablets
• 1 ) Weight variation :
 Ten tablets are selected randomly from the lot and
weighed individually to check for weight variation.
 A maximum of 10 % wt. variation is allowed based on
tablet wt.
• 2) Hardness :
 Tablets require a certain amount of strength or hardness
and resistance to friability, to withstand mechanical
shocks during handling , packaging and shipping.
 The hardness of the tablet is determined by using a
Monsanto hardness tester.
 It is expressed in kg / cm2.
3) Thickness :
The thickness of three randomly selected tablets are measured by
Vernier Caliper.
It is expressed in mm.
4) Friability :
The friability of the tablet is determined using Roche Friabilator.
It is expressed in %.
10 tablets are initially weighed and transferred into the friabilator.
The friabilator is operated at 25 rpm for 4 mins. The tablets are
weighed again to determine the percentage loss.

Friability of tablet should not exceed 1%.

• 5) Content uniformity:

 Ten tablets are weighed .

 The tablets are powdered. The powder equivalent to
100 mg of drug is weighed.
 It is dissolved in a solvent in which the drug is soluble.
 The concentration of the drug is measured by
determining the absorbance in a UV-Visible
Spectrophotometer, at the 𝜆 _𝑚𝑎𝑥 of the drug.
6) Surface pH
 The surface pH of the buccal tablets is determined in order
to find out the possibility of any side effects in buccal
environment.
 As an acidic or alkaline pH may cause irritation to the
buccal mucosa, it is determined to keep the surface pH as
close to buccal pH as possible.
 The tablet is allowed to swell by keeping it in contact with
5 ml of phosphate buffer containing 2% w/v agar medium
(pH6.8±0.01) for 2 h at room temperature.
 The pH is measured by bringing the electrode in contact
with the surface of the tablets and allowing it to equilibrate
for 1minute. A mean of three readings are recorded.
• 7 ) Swelling index:
One tablet from each batch is weighed individually and
placed separately in a thoroughly cleaned Petri dish containing
5ml of pH 7.2 phosphate buffer.
At regular intervals the tablets are removed .
The swollen tablets are reweighed & swelling index is
calculated by using the formula:

Swelling index = [(W2-W1)/W1] × 100

Where, W1- Initial weight of Tablet,

W2- Weight of swollen tablet at time(t).

8)In-vitro dissolution studies :
 The In-vitro dissolution study can be conducted as
per the United States Pharmacopoeia (USP).
 The rotating paddle method is used to study the drug
release from the tablets .
 The dissolution medium is 900 mL of phosphate
buffer (pH 6.8).
 The study is performed at 37°C ± 0.5°C, at a rotation
speed of 50 rpm.
 5 mL samples are withdrawn at predetermined time
intervals (1 to 7 h) and the volume was replaced with
fresh medium.
 The samples are filtered through Whitman filter
paper No.40 and analyzed after appropriate dilution
by UV spectrophotometer at suitable nm.
 The % drug release was calculated using the
calibration curve of the drug in phosphate buffer .
9) Stability studies:
 The purpose of stability study is to provide evidence on the
quality of a drug product, which varies with time under the
influence of a variety of environmental factors such as
temperature, humidity and light.
 The stability studies are conducted as per ICH guidelines.
 The tablets are sealed in aluminium packaging and kept in
humidity chamber at 30±2°C with 65±5% RH for 2months.
 The samples are taken out at 0, 30, 40, 50 and 60 days.
 The tablets are then analysed for drug content and in vitro drug
release profile.
 Buccal Patches / films
They are long, flat, thin, transparent with high surface area.
They can be prepared by two methods
1. Solvent casting method
2. Direct milling method

Solvent Casting Method

The drug & all excipients are weighed and dispersed in a suitable
organic solvent & coated on the release liner.
The organic solvent is allowed to evaporate & after evaporation a thin
layer of the backing material is applied on to the sheet of coated release
liner to form laminate.
After this the whole patch is ready to cut into required size.
 Direct milling Method
 In this method, the patches are manufactured without
the use of solvents.
 Drug and excipients are mechanically mixed by direct
milling or by kneading, usually without using any
liquids.
 After the mixing process, the resultant material is rolled
on a release liner until the desired thickness is achieved.
 The backing material is then laminated as previously
described.
 This solvent-free process is preferred because there is no
possibility of residual solvents and no associated solvent-
related health issues.
 Evaluation of buccal patches
1 ) Thickness :
 The thickness of each patch was measured using screw gauge
at five different positions of the patch and the average was
calculated.
2) Uniformity of weight :
 Patches of size 1x1 cm2 are cut. The weights of five patches
were taken individually on an analytical balance and the
average weight is calculated.
3) Assay :
 A complete patch from a Teflon mold was cut into pieces and
crushed in a mortar under a water/ethanol solvent system
 The contents are then filtered through a Whatman
filter paper.

 About 10ml of filtrate is transfered into a 100ml

volumetric flask

 After appropriate dilution with phosphate buffer (pH

6.8), solutions were analyzed by UV
spectrophotometer.

 Drug content was estimated from a calibration curve

• 4 )Folding endurance :

 Folding endurance was determined manually,

by repeatedly folding a patch at the same place
until it ruptures. (300 times)

 The number of folding required to break or

crack a patch was taken as the folding
endurance.
 5) In vitro drug release :
• Experiments are performed in triplicate using an orbital shaker
maintained at 37±0.5 °C and at 100 strokes per min.

• Patches were firmly secured in modified glass bottles (125 mL)

placed on the shaker platform and 100 mL phosphate buffered
saline( pH 6.8) added as the dissolution medium.

• At specified times, 2 mL is removed using a syringe and replaced

with equal volumes of fresh PBS to maintain the total volume.

• Samples were filtered through a 0.45 μm Millipore® Filter and

drug concentration determined by measuring absorbance at
suitable nm.
 • Buccal gels and ointments

 It has the advantage of easy dispersion, but drug dosing

may not be accurate.
 Hence mainly used for local action .
 Poor retention of gels at site of application has been
overcome by using bioadhesive polymers in the
formulation .
 Examples – SCMC, carbopol, xanthum gum
 Polymers change their form, from a liquid to semisolid
state which enhances viscosity, that results in
controlled and sustained release of drugs .
 Evaluation of buccal gel
1) Determination of PH:
 The PH of the gel was determined using a calibrated
pH meter.
 The average of 3 readings are taken.
2) Measurement of Gel Strength:
 A sample of 50 Gms of gel was
placed in a 100ml graduated
cylinder and maintained at 37 ° c.
 The apparatus for measuring gel
strength (weigh or apparatus as
shown in figure ,weighing 27 gm)
was allowed to penetrate in gel.
 The gels strength, which means
the viscosity of the gels at
physiological temperature, was
determined by the time (seconds),
the apparatus took to sink 5cm
down through the prepared gel.
3)Drug release study:

 The drug release study of bioadhesive gel was carried out

with modified Franz diffusion cell.
 Specially designed diffusion tubes with internal diameter
of 2cm having cellophane membrane at one end were used.
 2gm gel was placed inside the tube.
 This assembly was immersed in a beaker containing 20 mL
of Phosphate buffer (pH 6.8) placed over a thermostatically
controlled magnetic stirrer set at 37±1°C.
 The contents in the beaker were stirred with the help of a
teflon coated bead at 300 rpm.
 The samples (2mL) were withdrawn at predetermined
intervals of 0,30mins, 1, 2, 3, 4, 5 and 6 h and replaced with
phosphate buffer (pH 6.8) to maintain the sink conditions.

 The drug content in the sample was analysed spectro

photometrically .

4 ) Stability studies :
• Shelf life as a function of time and storage temperature was
evaluated by visual inspection of the bioadhesive gels at
different time periods.

 Stability was monitored at 4°C, 25°C and 50°C.

 Buccal lozenges
• The tablet is a flat faced at least about 18mm in diameter
and meant to suck and dissolves in the mouth.
• The compressed tablet is called troches and the tablets
produced by fusion or candy molding process are called
lozenges.
• Flavours and sweeteners are added to make tablets
palatable.
• The tablet generally contains sucrose or lactose and
gelatin solution to impart smooth taste.
• Lozenges for local action in mouth/ throat are: antiseptics,
antibiotics, demulcents, antitussive agents or astringents.
To produce systemic action: multivitamin tablet.
 Advantages:
 Elimination of first pass metabolism , good bioavailability.
 Rapid onset of action.
 Drug release for a prolonged duration .
 Permeation is faster with respect to Skin (4-4000).
 Large surface area with respect to sub-lingual mucosa.
 Good patient compliance with respect to parental
 Easy administration & removal in case of toxicity.
 Can be administered to unconscious patients.
 Limitations
Drugs with bitter taste or irritant to mucosa or having
noxious smell cant be administered.
Not usually for children.

Eating & drinking becomes difficulty.

Due to Salivary erosion, portion of drug may enter GIT.

Less surface area than skin.

Drugs unstable at Buccal pH(6.5 to 7) cannot be
administered.
 REFERENCE
Controlled and Novel Drug Delivery - N.K.Jain

Novel Drug Delivery System, 2nd edition -

Yie.W.Chien
Advances in Drug Delivery,1st volume -Y
Madhusudan rao & A V Jithan.
Encyclopaedia of controlled release-volume1
International journal of pharmaceutical science and
research.
 Questions
• 1)Define and classify buccal drug delivery
system.Discuss the factors affecting
mucoadhesion.(20 marks)
• 2)List out the advantages and disadvantages
of buccal drug delivery system and explain the
evaluation parameters of bioadhesive patches.
(20 marks)
 THANK YOU

PRAKASH G YARAGATTI
1ST M Pharm Pharmaceutics
GCP Bengaluru