الفهرس 
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Abstract
Solid dosage forms represent a great share of the pharmaceutical production due
to being; stable, easier for shipping and handling and have longer expiration
dates. In addition, solid dosage forms require less shelf space, do not require
preservation and have accurate dosage (single dose).
Coating represents a very important operation during the production of solid
dosage forms either due to enhancing tablet flowability and line clearance or due
to functional and patient adherence related issues.
Polymeric film coating is characterized over other coating methodologies by its
quality, operational efficiency, safety and profit. Aqueous-based systems have
gained popularity over solvent-based systems due to their lower toxicity levels
and environment friendly standpoint.
Eudragit® acrylic resins have been widely used in the pharmaceutical industry,
they are characterized by being water insoluble but swellable polymers.
Antiadherents are very common additives during aqueous acrylic polymeric
film coating so as to avoid susceptible stickiness or tackiness of polymeric films
which is a concern during both coating process and storage.
Talc is considered to be one of the most frequently used antiadherents specially
in the Egyptian market due to its low price and is characterized by its
hydrophobic nature, Glyceryl monostearate (GMS) has been used as an
alternative for talc and is known by its waxy nature. The ready-to-use
PlasacrylTM T20 suspension which contains GMS as an antiadherent, triethyl
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citrate as a plasticizer and polysorbate 80 as a surfactant has been recently used
with Eudragit® polymers.
In spite of being a corner stone in the treatment of the unwanted tablet
agglomeration during coating, antiadherents may be causative factor for many
changes in either the physicochemical properties or the dissolution properties of
acrylic polymeric film coating systems.
Polymer films must be mechanically strong such that they do not break or
fracture during processing, packaging, shipping, and storage.
Generally, particles coated with a film behave differently from the film itself.
However, there is no doubt that studies conducted on free films help to
understand the behavior of dosage forms coated with these films. Free films can
be obtained by the casting method, where a polymeric solution or dispersion is
cast onto a nonstick substrate and the solvent is evaporated. To avoid different
film surfaces that may result from casting the polymeric dispersions; a spray
atomization technique was also employed.
Tensile testing of free films has been the most common method used for
studying the physical-mechanical properties of polymers by measuring some
parameters such as stress at break, percentage strain at break, work to break and
elastic modulus which give an indication for elasticity, strength and toughness of
the films. Further parameters may be also calculated from tensile testing such as;
tensile strength to Young’s modulus ratio, relative surface energy and toughness
index.
The mechanical properties of a polymer may be characterized as follows:
A soft and weak polymer which is characterized by low tensile strength and low
elongation, a hard and brittle polymer is defined by moderate tensile strength
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and low elongation, a soft and tough polymer is characterized by moderate
tensile strength and high elongation, whereas a hard and tough polymer is
characterized by high tensile strength and high elongation.
In terms of mechanical properties, an ideal film for coating should have a high
tensile strength, a large elongation at break and a high elastic modulus. Such
films will be hard and tough without being brittle.
Thermally, differential scanning calorimetry was used to measure the glass
transition temperature of the prepared films so as to give an indication for the
transition at which polymer changes from the glass to the rubbery state and for
film compatibility as well.
The water uptake or absorption behavior of the polymeric film coated on
pellets or tablets plays an important role at the beginning stage of drug release
from these solid dosage forms. Hence, the percentage loss on drying was
measured to indicate the level of water uptake of the prepared polymer films
which gives expectation for drug release from the coated formulation.
T-peel test was used to measure tackiness of the polymer films so as to
determine the optimum concentration at which investigated antiadherents start to
perform their function.
Compatibility or miscibility of a polymer blend was evaluated also visually by
optical appearance where, compatible polymer blends give clear films upon
drying. On the other hand, if miscibility is absent the obtained film will be
translucent or opaque. Surface deformities were also monitored microscopically.
In contrast to the study of free films, evaluation of applied films allows
evaluation of substrate variables, processing parameters, and storage conditions
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as well as coating formulation variables. The delayed release is intended to
release the drug after some delay or after tablet pass GI tract, enteric film
coatings exhibit pH-dependent solubility and have been used to protect drugs
from degradation in the stomach.
Acetylsalicylic acid tablets were used as model tablets for enteric coating in order
to characterize different applied Eudragit® FS30D polymer films.
The aim of this study was to prepare and evaluate characteristics of drug-free
films containing different amounts of talc and glyceryl monostearate in order to
determine their effect on the physicochemical properties of acrylic polymeric
films and on the drug release profile from model acetylsalicylic acid enteric
coated tablets so as to correlate effect of antiadherents on the properties of free
films and on the in-vitro release profile to determine optimum concentrations of
talc and GMS to be used with acrylic films without affecting either properties.
Knowing such information would decrease coating time and cost. Moreover, the
effect of antiadherent type and/or concentration on the release profile may help in
tailoring of the drug release.
The achieved work in this thesis as well as the obtained results can be
summarized as follows:
1 . Twenty eight different Eudragit® drug-free formulations (between sustained
release such as Eudragit® RL30D and Eudragit® RS30D and delayed release
such as Eudragit® FS30D formulations) were prepared as films using
different concentrations of each of the investigated antiadherents. Simple
differences were applied between each antiadherent formulae based on the
nature of each antiadherent, also a new casting technique has been used
using Teflon island system.
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2. Upon characterization of the prepared films, it was found that increasing talc
concentration from zero up to 100% w/w led to increasing abrasion
resistance, brittleness, stiffness and decreasing the work required to break
films and the ability of the polymer to absorb energy without fracture and
resulted in less desirable films.
3. Talc at 25% w/w concentration shows minimum significant effects on
mechanical properties mainly with Eudragit® RL30D, followed by
Eudragit® RS30D and Eudragit® FS30D. So, regarding mechanical
properties, 25% w/w talc concentration is recommended to be used with
those three polymers because of its insignificant effect on the measured
mechanical properties.
4. Glyceryl monostearate was found to decrease abrasion resistance, brittleness
and increase stiffness and work required to break films and to decrease the
ability of the polymer to absorb energy without fracture.
5. Comparing the effect of glyceryl monostearate on Eudragit® RS30D
polymer films to that on the Eudragit® RL30D films shows that GMS
forms better combination with Eudragit® RS30D regarding film
brittleness.
6. PlasACRYL™ T20 was found to increase brittleness and stiffness while,
decrease work required to break films and the ability of the polymer to
absorb energy without fracture and to form better combination with
Eudragit® RL30D films regarding film strength.
7. Upon addition of any of the investigated antiadherents, the behavior of the
polymer films during stress-strain testing and consequently their stress-strain
graphs were found to be changed from soft and tough films to hard and
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brittle talc films or hard tough GMS or PlasACRYL films. Talc at 25%
concentration was found to give very similar behavior to that of the control
formula.
8. The film-forming method was found to determine the characteristics of the
films, which lead to consider that the film-forming method should be as
similar as possible to that used in a pharmaceutical film-coating operation, in
order to obtain results that are more representative for the real coating
process.
9. Increasing antiadherent concentration, increased polymer glass transition
temperature which means increase in crystallinity and decrease in polymer
mobility which suggested significant delay in solute permeation.
Insignificant difference between the glass transition temperature values of
Eudragit® RS30D cast and sprayed films was found.
10. Like talc, GMS particles led to decrease water uptake upon being exposed
within the films to high humidity environment and decrease the % loss on
drying as a consequence with more significant decrease in Eudragit® RS30D
polymer films than Eudragit® RL30D.
11 . Talc was found to decrease tackiness of the polymer films in correlation to a
decrease in polymer chain mobility and increase in young’s modulus and
glass transition temperature.
12. Microscopic examination clearly indicates lowest surface deformities in talc
films, more in PlasACRYL™ T20 and highest surface deformities in GMS
polymer films and best compatibility with PlasACRYL™ followed by talc
while GMS showed least compatibility regarding surface deformities.
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13. Nine delayed release coating formulae were prepared using Eudragit®
FS30D as a delayed release model polymer and each one was coated at three
different coating levels.
14. The wavelength of maximum absorbance of acetylsalicylic acid was found
to be 275nm in 0.1N HCl, pH 1.2 and 265nm in 0.1N HCl: 0.2M Na3PO4
(3:1) buffer solution pH 7.4. Calibration curves for acetylsalicylic acid
solutions were assessed in both 0.1N HCl and phosphate buffer at their λmax.
15. Dissolution showed a negative correlation with mechanical strength and
initial release rate constant.
16. Increasing coating level caused delay in the acetylsalicylic acid release.
Increasing talc and GMS concentrations delayed drug release while
increasing PlasACRYL concentration showed increase in the release profile.
None of the used antiadherents affected gastric resistance of the used
polymer.
17. The lag time and drug release rate could therefore be controlled by
manipulating both the theoretical weight gain of the tablets and the
concentration of the added antiadherent at the same coating level. This study
reveals that talc and glyceryl monostearate at 9mg/cm2 coating level could
be used to prolong the drug release, offering improvement to the previously
reported polymer formulations by extending drug release lag time to meet
potential patient needs and to achieve controlled drug release at lower drug
loading by manipulating the levels of talc, GMS and the polymer itself.
18. The inner film structure strongly affects properties of the coatings (e.g.,
mechanical strength and permeability) and thus, the underlying drug release
mechanisms and profiles.
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19. Antiadherents were found to be one of the most important factors affecting
mechanical, thermal and dissolution properties of acrylic polymeric films.
20. Talc formulae at 6mg/cm2 and at 3mg/cm2 coating level with glyceryl
monostearate and PlasACRYL™ T20 formulae showed highest similarity
with the marketed tablets while 9mg/cm2 coating level showed the lowest
similarity values with all investigated formulae.