formulation and evaluation of fast dissolving oral film of prochlorparazine dimaliate

16 Pages·2016·0.76 MB·English

Journal of
Medical Pharmaceutical www.jmpas.com
And Allied Sciences ISSN NO. 2320 - 7418

RESEARCH ARTICLE

FORMULATION AND Correspondence
Rahul Kumar Sahu
EVALUATION OF FAST Department of pharmaceutics,
institute of p’ceutical sciences,
DISSOLVING ORAL FILM OF Bhopal.
Keywords
PROCHLORPARAZINE orodispersible, polymeric
film, , mucoadhesive, quick
DIMALIATE
release, antipsychotic
Received
Dr. Rathi Jagdish, Sahu Rahul Kumar*, Solanki Praveen, 08 December 2016
Reviewed
Kotwar Ramesh, Khan Nadeem, , Mathur Rahul
10 December 2016
Accepted
NRI institute of pharmaceutical sciences, Bhopal, India
14 December 2016

ABSTRACT
A oral fast dissolving film is a type of multiple new drug delivery system. aim and objective to
prepare and evaluate fast Dissolving oral film of Prochlorperazine to reduce the pain like
migraine with fast relief. Prochlorperazine oral film quickly disintegrates and dissolves, and can
be administered without water, making them particularly suitable for geriatric patients and found
faster action. The immediate release layer containing PEG600, HPMC, EC, Citric acid was
prepared by solvent casting method and fast release layer containing HPMC, EC, Citric acid (in

desired concentrations) was. The drug content of film revealed that the drug was uniformly
mixed in the polymers. In-vitro dissolution studies revealed that formulation has showed the
initial release of immediate release layer dose. The kinetic data showed that drug release from
film follow Zero order, Higuchi plot indicated that the formulation follow Diffusion controlled
release mechanism.

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INTRODUCTION to be viewed as an alternative for FDT
products that would afford a superior barrier
Oral drug strip oro-dispersible film to
to generic entry and product differentiation
administer drugs via absorption in the mouth
to over‐the‐counter brands. From the
(buccally or sublingually) and/or via the
marketing perspective, a patented ODF
small intestines. A film is prepared using
technology would be beneficial. The grant
hydrophilic polymers that rapidly dissolves
of marketing exclusivity to the new dosage
on the tongue or buccal cavity, delivering
form would help to gain more revenue. The
the drug to the systemic circulation via
various synonyms used for FDFs include
dissolution when contact with liquid is
mouth dissolving films (MDFs), orally
made. Thin-film drug delivery has emerged
disintegrating films (ODFs), melt in-mouth
as an advanced alternative to the traditional
films, oro-dispersible, quick dissolving and
tablets, capsules and liquids often associated
rapid disintegrating films (2).
with prescription and OTC medications.
Classification of Oral Films:
Similar in size, shape and thickness to a
There are three different subtypes
postage stamp, thin-film strips are typically
1. Flash release
designed for oral administration, with the
2. Mucoadhesive melt-away wafer
user placing the strip on or under the tongue 3. Mucoadhesive sustained-release wafers
(sublingual) or along the inside of the cheek Advantages:
(buccal). These drug delivery options allow 1. Improved bioavailability of poorly soluble
the medication to bypass the first pass compounds.
metabolism thereby making the medication 2. During Processing solvents and water are
more bio-available. As the strip dissolves, not required.
the drug can enter the blood stream, buccally 3. Cost-effective process with reduced
or sublingually (1). Evaluating the systemic production time and reduced number of unit
transmucosal drug delivery, the buccal operations.
mucosa is the preferred region as compared 4. Homogeneous distribution of fine particle
to the sublingual mucosa. Different buccal occurs.
delivery products have been marketed or are 5. Sustained modified and targeted release
proposed for certain diseases like trigeminal capability.
neuralgia, Meniere's disease, diabetes, and 6. Superior stability at varying pH and
addiction. The FDFs technology continues moisture levels (3).
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MATERIALS AND METHODLOGY A small quantity of powder was placed into
a fusion tube. That tube is placed in the
Prochlorperazine was obtained as a gift
melting point determining apparatus
sample from Sun Pharma Ltd, Varodra.
containing castor oil. The temperature of
Other Excipients were procured from
the castor oil was gradual increased
Rankem/SD Fine Chemicals.
automatically and read the temperature at
Pre-formulation study
which powder started to melt and the
A) Organoleptic evaluation
temperature when all the powder gets
It refers to the evaluation by sensory
melted.
characters-taste, appearance, odor etc.

B) Solubility (at room temp :)Solubility is
F) Moisture Content Determination
determined in different solvents example –
The titrimetric determination of water is
water methanol, 0.1 N HCL, Ethyl Alcohol,
based upon the quantitative reaction of water
and Chloroform (4).
which is present on sample with KF reagents
C) Loss on drying:
and record % of water (6).
Loss on drying directly measuring by IR
G) Determination of λ
max.
moisture balance. Firstly calibrate the
The absorption maxima of Prochlorperazine
instrument by knob then take 5.000 gm
dimaleate were determined by Accurately
sample (powder) and set the temp at 100°C
weighed 10 mg of drug was dissolved in 10
to 105°C for 5 minutes and constant reading
ml of 6.8 pH phosphate Buffer in 10 ml of
set the knob and check % moisture.
volumetric flask and prepare suitable
D) Determination of pH (1 w/v solution
dilution to make it to a concentration of
in water)
10μg/ml make adequate of sample with
pH was determined by digital pH meter. In
concentration range of 5-25μg/ml. The
this method 1gm of the powder was taken
spectrum of this solution was run in 200-400
and dissolved in 100ml of distilled water
nm range in U.V spectrophotometer
with sonication and filtered, pH of the
(Labindia UV 3000 +) (7).
filtrate was checked with standard glass
electrode (5).

E) Melting point:

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Formulation controlled by covering with a funnel in its
The method of solvent casting technique inverted position. After 24 hours the films
involves preparation of the film base which were removed, cut in circular disc with
involves the mixing of suitable film forming 3.8cm diameter and kept in desiccators for
excipients along with drug in a suitable further studies (9). The composition of
solvent or solvent system. Once the solution various polymeric combinations is given in
is prepared, the film casting process is the Table. 1
performed wherein a film of desired Name of Ingredients Composition
Prochlorperazine 120mg
thickness is casted onto a moving inert
dimaleate
substrate, where suitable rollers are HPMC 200
EC 100
employed for guiding the solution onto the
PEG-600 0.5
substrate (8). SSG 10
CCS 10
formulation of oral fast dissolving films of
Citric Acid 10
Prochlorperazine dimaleate done by solvent
DM Water 20 ml
casting methodformulation done by
combining the polymers in different ratios. EVALUATION PARAMETERS 10, 11
HPMC and EC films were prepared by A) Thickness
dissolving HPMC in measured volume of The thickness of patches was measured at
chloroform. Then added EC and mixed three different places using a absolute
thoroughly to get a homogeneous mixture. outside micrometer.
To this, specified quantities of dibutyl
phthalate and isopropyl myristate were B) Weight uniformity
added. The polymeric solution of EC and For each formulation, three randomly
HPMC were prepared by dissolving selected patches were used. For weight
separately in methanol- chloroform (1:1) variation test, 3 films from each batch were
mixture. A weighed amount of drug was weighed individually by digital electronic
dissolved in DM water and dispersed in balance and the average weight was
polymer mixture, then added PEG-600, SSG calculated (10).
, CCS Citric Acid, and poured in to the glass The tensile testing gives an indication of the
mould placed in a hard rigid and uniformly strengthand elasticity of the film, reflected
leveled surface. Solvent evaporation was
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459
by the parameters- tensile strength, elastic disintegrating time. Three super
modulus, % strain, and loadat yield. disintegrating agent were selected for this
work (15).
C) Folding Endurance
G) In vitro dissolution study
This was determined by repeatedly folding
The in vitro dissolution test was performed
one film at the same place until it broke. The
using the USPXXX dissolution apparatus II
number of times the film could be folded at
(Paddle with sinker). The dissolution studies
the same place without breaking / cracking
were carried out at 37±0.5° C; with stirring
gave the value of folding endurance (11).
speed of 75 rpm in 900 ml 0.1 N
D) Percentage of Moisture Content
Hydrochloric acid. Film size required for
The films were weighed individually and
dose delivery (2.5×2.5 cm2) was used. Five
kept in desiccators containing activated
ml aliquot of dissolution media was
silica at room temperature for 24 hrs.
collected at time intervals of 1, 2, 5, 10 and
Individual films were weighed repeatedly
15 minutes and replaced with equal volumes
until they showed a constant weight. The
of 6.8 N HCl. The collected samples were
percentage of moisture content was
filtered through 0.45 μm membrane filter
calculated as the difference between initial
and the concentration of the dissolved
and final weight with respect to final weight
Prochlorperazine dimaleate was determined
(12).
using UV-Visible spectrophotometer at 256

nm. The results were presented as an
E) Drug Content Analysis
average of three such concentrations (16-
The film of specified area were taken into a
18).
10 ml volumetric flask and dissolved I in
RESULTS AND DISUSSION
methanol and volume was made up with 10
Solubility studies of Prochlorperazine
ml methanol. Subsequent dilutions were
dimaleate has been done in various solvent
made and analyzed by UV
such as water, Chloroform, Ethanol,
spectrophotometer (13-14).
Methanol, and 0.1N HCL solution. We were
F) Disintegrating time
found that a solubility of Prochlorperazine
The most important criteria of present work
dimaleate is good in a Methanol solution.
are to that dosage form should be dissolved
The melting point of the drug sample range
within few seconds. The incorporation of
of the drug is 140-142oC. Hence complies
super disintegrating agent to minimizes the
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460
with IP standards thus indicating the purity processing, packaging, transport and
of the drug sample. handling. The desirable characteristics of
film are moderate tensile strength, low
The partition coefficient is a ratio of
elastic modulus, high% strain and high load
concentrations of un-ionized compound
at yield. From the above table, the polymer
between the two solutions. To measure the
should give soft but tough film.
partition coefficient of ionizable solutes,
disintrigation time of this batch also suitable
the pH of the aqueous phase is adjusted such
fast disintegration oral film aimed about 25
that the predominant form of the compound
sec.
is un-ionized.
The most important criteria of present work
The percentage of loss on drying of
are to that dosage form should be dissolved
Prochlorperazine dimaleate was found to be
within few seconds. The incorporation of
0.92% w/w respectively.
super disintegrating agent to minimizes the
The pH of Prochlorperazine dimaleate was disintegrating time. Three super
determined by Digital pH meter and found disintegrating agent were selected for this
to be 7.6. The Moisture content of work.
Prochlorperazine maleate is 0.56 %. The In vitro drug release data of the
Accurately weighed 10 mg of optimized formulation was subjected to
Prochlorperazine dimaleate separately and goodness of fit test by linear regression
dissolved in 10 ml of 6.8 pH buffer in 10 ml analysis according to zero order, first order
of volumetric flask and prepared suitable kinetic equsation in order to determine the
dilution to make it to a concentration of mechanism of drug release. When the
10μg/ml make adequate of sample with regression coefficient values of were
concentration range of 5-25μg/ml compared, it was observed that ‘r’ values of
Prochlorperazine dimaleate. The spectrum first order was maximum 0.949 hence
of this solution was run in 200-400 nm range indicating drug release from formulations
in U.V spectrophotometer. the λmax found for was found to follow First order release
Prochlorperazine dimaleate is 256.0 nm. kinetics.
The mechanical properties of the film give
idea about to what extent the film can

withstand the force or stress during
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7. Hariharan M, Bogue A. Orally
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Table No. 2 Organoleptic property of Prochlorperazine Dimaleate
Color : Light yellow powder
Odor : Odorless
Taste: : Bitter

Table No. 3. Solubility studies of Prochlorperazine dimaleatein different solvent
S. Solvent used Solubility
No.
1. Water Insoluble
2. 0.1 N HCL Sparingly soluble
3. Ethanol Sparingly soluble
4. Methanol Freely Soluble
5. Chloroform Sparingly soluble
6. 6.8 pH buffer Freely soluble

Table No. 4 Description of IP-Index

Descriptive term Parts of solvent required for

Parts of soluble

Very soluble Less than 1

Freely soluble From 1to 10

Soluble From 10 to 30

Sparingly soluble From 30to 100

slightly soluble From 100 to1000

Very slightly From 1000 to 10000
soluble

Practically insoluble 10000 or more

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Figure no. 1 DETERMINATION OF Λ BY UV-VISIBLE SPECTROSCOPY
max

Fig No.1 Determination of λ of Prochlorparazine dimeliate
max

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