Preparation and Characterization

7. PREPARATION AND CHARACTERIZATION

Different approaches used for preparation of fast dissolving systems like

Lyophilized system, compressed tablet based system and Oral thin wafers/strips.
Oral thin film/wafers are the most convenient and advanced form of oral solid
dosage form due to the efficiency of dissolving within minutes in oral cavity when it
comes in contact of saliva. It neither requires chewing nor water for administration.
It gives quick absorption and instant bioavailability of drugs due to the high blood
flow and permeability of oral mucosa.

7.1 Formulation development of Sublingual wafers of Palonosetron

Various approaches to manufacturing of rapid dissolving wafers are classified as

follows:
A. Casting and drying—(a) solvent casting (b) semi-solid casting
B. Extrusion—(a) hot-melt extrusion (b) solid dispersion extrusion
C. Freeze dried wafers
D. Rolling method

Solvent casting method

This technique is employed to manufacture fast dissolving wafers of size 3x2 cm 2

and 2.5x2.5 cm2. Water soluble polymers are dissolved in the aqueous vehicle. The
drug along with other excipients is dissolved in a suitable solvent, and both are
mixed and stirred. It is finally casted on petridish or plate made up of glass, plastic
or Teflon and dried. Specific types of equipment are used at large scale production
as well as rollers are used for pouring the solution on an inert base. Entrapped air is
removed by vacuum. The final step is drying the wafer, removes the solvent and
helps to obtain the finished product. Wafers are dried after which cutting, stripping
and packaging is done. Due to feasibility and easy to preparation with lower cost,
Solvent casting method used for formulation development of thin wafers of
Palonosetron.

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 Preparation and Characterization

7.1.1 Casting process of fast disintegrating oral wafers

Various methods are available for casting of oral wafers. This is fast disintegrating
oral wafers hence on the laboratory scale solvent casting technique was adopted for
formulation of wafers.

7.1.2 Solvent casting technique

Drug (Palonosetron) containing fast dissolving wafers were fabricated by the solvent
casting method. Xanthan gum, Gelatin, Gum acacia, cross carmellose sodium,
Aspartame by solvent casting technique with ice cold distilled water and sublingual
wafers were prepared. Drug solution was sonicated for 30-45 min to solubilize the
drug completely in the solvent. Drug solution was poured into polymeric solution
and ethanol was added for alkaline hydrolysis. Both solutions are uniformly mixed to
get a homogeneous solution on magnetic stirrer at 250-320 rpm. Then this solution
was spread on film former by adjusting the desired temperature on glass moulds of
15cm*5 cm2. Once the wafer sheet was ready, it was cut into desired size of 2.5*2.5
cm2 cm was dried and The dried wafers were carefully removed from the glass plates
and was cut into size required for testing. The wafers were stored in air tight plastic
bags till further use. The composition of sublingual wafers is given in Table 7.1.

7.1.3 Parameter Selection for formulation of oral wafers

1. Size of Wafers

Size of tongue is about 2.5 x 2.5 cm, to provide sufficient space for dissolving in
oral cavity by putting wafers on tongue for swishing or hydrating with saliva, size
2.5 x 2.5 cm were concluded as unit dose of Wafers.

2. Fabrication of wafers casting glass reservoir

Wafers casting glass reservoir is most important glassware which was fabricated
keeping view the following aspect:

1. No. of wafers in one batch

2. Holding capacity of formulation solution for drying

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 Preparation and Characterization

3. scrapping-off wafers from Wafers casting glass reservoir

4. Easy to positioned horizontally with gravity for uniform formation of wafers

A 15.0 x 5.0 cm sized Wafers casting glass reservoir was fabricated having depth of
0.5cm. This sized Wafers casting glass reservoir will produce twelve 2.5 x 2.5 cm.

3. Amount of solution for formulation

30.0 ml solution was calculated for further study, because this will produce 200
micrometer depth for solvent evaporation and sufficient numbers of wafers for
further evaluations.

4. Temperature and time of drying

Preliminary study suggests that 40+/- 1.0degree centigrade for 12 hrs adequately dry
the wafers.

5. Speed of mixing at magnet stirrer.

250-320 rpm speed for first 30 minutes were optimized for entire study and 5
minutes for all ingredients with same speed were finalized.

7.1.4 Selection and optimization of wafers forming agents

Two wafers forming agents and one co-wafers forming were selected for this
research work. The concentration of wafers forming was important to form a proper
thickness for appropriate packaging and handling of oral wafers.

Concentration of wafers forming agent is optimized on the basis of thickness and

appearance of wafers.

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 Preparation and Characterization

A) Optimization of formulations
Table No 7.1: Selection and Optimization of Wafers Forming Agents

Name of ingredients
(mg for 12 strips) F1 F2 F3 F4 F5 F6 F7 F8 F9

API 6 6 6 6 6 6 6 6 6

Xanthan gum 50 100 150 50 100 150 50 100 150

Gelatin 10 20 30 10 20 30 10 20 30
Gum acacia 25 50 75 25 50 75 25 50 75
Cross carmellose sodium 10 10 10 10 10 10 10 10 10
Methyl Paraben 10 10 10 10 10 10 10 10 10
Aspartame 10 10 10 10 10 10 10 10 10
Citric acid 15 15 15 15 15 15 15 15 15
DM water qs to (ml) 30 30 30 30 30 30 30 30 30

Dose calculations
 Width of the plate = 5cm
 Length of the plate = 12cm
 No. of 2.5 x 2.5 cm2 wafers present whole plate = 12
 Each wafer contains 0.5 mg of drug.
 12 no. of wafers contains mg of drug? = 0.5×12 = 6mg
 The amount of drug added in each plate was approximately equal to 6mg.

7.2 Evaluation of prepared Wafers

7.2.1 Thickness
Three random wafers were selected from each batch and the thickness was measured
at three different places using a vernier caliper.

7.2.2 Weight uniformity

For each formulation, three randomly selected patches were used. For weight
variation test, 10 wafers from each batch were weighed individually by digital

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 Preparation and Characterization

electronic balance and the average weight and relative standard deviation was
calculated.

7.2.3 Surface pH Determination

The surface pH of fast dissolving wafers was determined in order to investigate the
possibility of any side effects in vivo. As an acidic or alkaline pH may cause
irritation to the oral mucosa, it is important to keep the surface pH as close to neutral
as possible. The wafer to be tested was placed in a petridish and was moistened with
0.2 ml of distilled water. The electrode of pH meter (Electronic india) was placed on
the surface of wafer to determine the surface pH.

7.2.4 Folding Endurance

This was determined by repeatedly folding one wafers at the same place until it
broke. The number of times the wafers could be folded at the same place without
breaking cracking gave the value of folding endurance.

7.2.5 Percentage of Moisture Content

The wafers were weighed individually and kept in desiccators containing activated
silica at room temperature for 24 hrs. Individual wafers were weighed repeatedly
until they showed a constant weight. The percentage of moisture content was
calculated as the difference between initial and final weight with respect to final
weight.
Initial weight−Final weight
Percentage of Moisture Content = x 100
Initial weight

7.2.6 Drug Content Analysis

The patches (n=3) of specified area were taken into a 10 ml volumetric flask and
dissolved in methanol and volume was made up with 10 ml methanol. Subsequent
dilutions were made and analyzed by UV spectrophotometer at 222nm.

7.2.7 Disintegrating time

The most important criteria of present work are to that dosage form should be
dissolved within few seconds. The incorporation of polymers to minimizes the

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 Preparation and Characterization

disintegrating time. In vitro disintegration time was determined by placing the wafer
in a petridish containing 10ml distilled water with swirling every 10 sec. The time at
which the wafer disintegrated was noted.

7.2.8 In vitro dissolution study

The in vitro dissolution test was performed using the USPXXX dissolution
apparatus II (Paddle type). The dissolution studies were carried out at 37±0.5°C;
with stirring speed of 50 rpm in 900 ml phosphate buffer (pH 6.8). Wafers size
required for dose delivery (2.5×2.5 cm 2) was used. Five ml aliquot of dissolution
media was collected at time intervals of 1, 2, 5, 10 and 15 minutes and replaced with
equal volumes of phosphate buffer (pH 6.8). The collected samples were filtered
through 0.45 μm membrane filter and the concentration of the dissolved
Palonosetron was determined using UV-Visible spectrophotometer at 222nm. The
results were presented as an average of three such concentrations.

7.9 Stability studies

Stability studies were carried out with optimized formulation which was stored for a
period of one, two and three months at 40±2oC temperature and 75±5% relative
humidity for a period 3 months. The % Assay of formulation was determined by
U.V. spectrophotometer using calibration curve method. The % assay of wafers was
found to slightly decrease at higher temperature.

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