Usually conventional dosage form produce wide ranging
fluctuation in drug concentration in the blood stream and tissues with
consequent undesirable toxicity and poor efficiency. This factor such as
repetitive dosing and unpredictable absorption generated the idea of controlled
drug delivery systems. The goal in designing sustained or controlled delivery
systems is to reduce the frequency of the dosing or to increase effectiveness
of the drug by localization at the site of action, reducing the dose required
or providing uniform drug delivery. The principal objective of sustained
release drug delivery is to make sure safety and to improve efficacy of drugs
as well as patient compliance.(Banker G S et al., 1990) Bi-layer
tablet is ideal for sequential release of two drugs in combination, separate
two incompatible substances and also for sustained release tablet in which one
layer is immediate release as initial dose and second
layer is maintenance dose.(Chein YW et al., 1992)There is various
application of the bi-layer tablet it consist of monolithic partially coated or
multilayered matrices. In the case of bi-layered tablets drug release could be
rendered almost unidirectional if the drug could be incorporated in top of the
non-adhesive layer its delivery occurs into the whole oral cavity.
From various current methods for treating
illness and diseases, chemotherapy (treatment with drugs) is the absolute most
commonly used technique. It has the broad array of applications over the
greatest selection of disease states and is generally the most well-liked
treatment method.(Banker G S et al.,1990) For all decades, treatment of
acute disease or chronic illness has been mostly accomplished by delivery of
drugs to patients using various pharmaceutical dosage forms including tablets,
capsules, pills, suppositories, creams, ointments, liquids, aerosols and
injectables as drug carriers. (Chein YW et al., 1992, Herber.A.Lieberman et
al.,1987) However, if it is a practical option, oral drug delivery is likely to
be chosen in all but the absolute most exceptional circumstances. Moreover, if
the oral route isn’t immediately viable, pharmaceutical companies will often
invest resources in which makes it viable, as opposed to plumping for an
alternative delivery system. Oral route of drug administration have wide
acceptance around 50-60% of total dosage forms and is the absolute most
convenient and preferred route for systemic effects because simple dosing
administration, pain avoidance, accurate dosage, patient compliance and
flexibility in formulation (Guncel W.C et al., 1989, Dahiya A et al., 2011,
Sharma A et al.,2011, Sampath Kumar K P et al., 2010).
Conventional dosage form are accused of
repetitive dosing and unpredictable absorption window that cause wide range of
fluctuation in drug concentration in the blood stream and tissues with
subsequent undesirable toxicity and poor therapeutic efficiency.(Divya .A et
al.,2011) This dynamic such as for instance repetitive dosing and
irratic absorption generated the thought of controlled drug delivery systems.
Formulation of layers from different polymers allows manipulation over multiple
rate-controlling polymer, thus enabling several types of drug delivery of a
number of drugs, i.e. where in fact the drug may be released with a bolus and
then at a controlled rate or by targeted drug delivery in the GI tract using pH
dependent polymers.(Micheal AE et al.,) The aim in designing
sustained or controlled delivery systems is always to decrease the
frequency of the dosing or to boost effectiveness of the drug by localization
at your website of action, reducing the dose required or provide uniform drug
delivery. The main objective of sustained release drug delivery is to ensure
safety and to improve effectiveness of drugs as well as patient compliance. But
often this controlled drug delivery system fails to achieve the stated
advantages because of insufficient releasing the original bolus dose. dose
dumping and failure to achieve site specific drug delivery.(Shiyani B et al.,,
2008) Immediate release drug delivery system is designed to disintegrate
rapidly, and exhibit instant drug release. It’s associated with fluctuations in
drug plasma levels, leading to reduction or loss in drug effectiveness or
increase incidence of side effects. Administration of the DDS several times per
day is therefore necessary to pay the decrease in drug plasma concentration
because of metabolism and excretion. A relatively constant plasma amount of a
drug is usually preferred to maintain the drug concentration within the
therapeutic window. However, it’s difficult to achieve, especially for
once-daily dosage forms, partly because the surroundings for drug diffusion
and/or absorption varies along the gastrointestinal (GI) tract. On the basis of
those considerations, we’ve proposed a bilayer tablet.(PreetiKarwa et
al.,2011,Patel G M et al.,2010).
Direct compression (DC) is the absolute most preferred
because of simplicity, rapidity, economic reasons and stability concerns. Hence
for just about any active pharmaceutical ingredient (API), ultimately the
formulator strives to produce in DC tablet form. Recently there were several
patents filed on DC technology.
Tablet manufacturing by
direct compression has increased steadily within the years. It provides
advantages over another manufacturing processes for tablets, such as for
example wet granulation and provides high efficiency. As direct compression is
more economic, reducing the cycle time and easy when it comes to good
manufacturing practice requirements. On another hand wet granulation not just
increases the cycle time, but even offers certain limits imposed by
thermolability and moisture sensitivity of the active. So pharmaceutical
industry has become focusing increasingly with this process. The unnecessary
exposure of any drug to moisture and heat can never be justified. Tablets made
by direct compression method give lower microbial levels than those prepared by
the wet granulation method. The compaction process exerts lethal impact on the
survival of microorganisms. The tablets prepared by direct compression
disintegrate into API particles as opposed to granules that directly come into
contact with the dissolution fluid and exhibit a comparatively faster
dissolution. The serious limitation of direct compression is the employment
greater than 30% of the drug in the formulation, mainly for drugs that present
low flowability and segregation.
Manufacturing steps for
compression involves comparatively few steps:
Milling of drug and excipients.
Mixing of drug and excipient
A great direct
compression excipient should possess these attributes
It should have good compressibility.
It should possess good hardness after compression, that
is material should not possess any deformational properties; otherwise
this may lead to capping and lamination of tablets.
It should have good flowability.
It must be physiologically inert.
It must be suitable for wide variety of API.
It must be stable to various environmental conditions
(air, moisture, heat, etc.).
It should not show any physical or chemical change in
its properties on aging.
It should have high dilution potential. i.e. Able to
add high quantity of API.
It must be colorless, odorless and tasteless.
is a metabolic disorder characterized by hyperglycemia, glycosuria,
hyperlipidemia, negative nitrogen balance and sometimes ketonemia. An extensive
spread pathological change in thickening of capillary basement membrane,
upsurge in vessel wall matrix and cellular proliferation resulting in vascular
complications like lumen narrowing, early atherosclerosis, sclerosis of
glomerular capillaries, retinopathy, neuropathy and peripheral vascular
Two Major Types Of
Diabetes Mellitus Are: (Bhavani harika et al., 2012.)
I / insulin dependent diabetes
mellitus (IDDM) juvenile onset diabetes mellitus.
It’s indicated by
lack of the insulin-producing beta cells of the islets of langerhans in
the pancreas leading to insulin deficiency. Type 1 diabetes make a
difference children or adults and it is termed as “juvenile diabetes”
as it represents a majority of the diabetes cases in children. Type 1 diabetes
mellitus could be managed by the administration of insulin.
II / non
insulindependentdiabetesmellitus (NIDDM), maturityonsetdiabetesmellitus.
Previously it had
been called as “adult-onset diabetes” because it had been usually
discovered after age 40. Type II diabetes contains about 90 percent of cases of
diabetes. With this sort of diabetes there’s no loss or moderate lowering of ?
cell mass, insulin in circulation is low, normal or even high.
Early Signs Of
Hyperglycemia In Diabetes Include:(panchalhitenashok et al., 2012)
Polydipsia (increased thirst)
Difficulty in concentrating
Polyuria (increased urinary output)
Ketonemia and ketourea (presence of ketone bodies in
the blood and urine respectively)
Blur sight, Fatigue (weak, tired feeling)
Itches on skin and mucus membranes
Outstanding tiresomeness/lack of energy.
Sudden weight reduction, Blood glucose a lot more than
In Diabetes May Result In:
Vaginal and skin infections.
Slow-healing cuts and sores.
Nerve damage results in painful cold or insensitive
feet, lack of hair on the low extremities, and/or erectile dysfunction.
Stomach and intestinal complications such as for
example chronic constipation or diarrhea.
1.1.1 Oral hypoglycemic
drugs:(Park C R and Munday D L et al., 2002, Pranjal Kumar
Singh et al.,2011.)
The following are the
different classes of drugs useful for treatment of diabetes
Glibenclamide, Glipizide, Gliclazide, Glimepiride.