FORMULATION OF COMBINATION

OF ORAL DOSAGE FORM OF

LAMIVUDINE AND COBICISTAT FOR
A SYNERGISTIC EFFECT FOR
HEPATITIS B
PRESENTED BY
D.SWARUPA RANI
(MPHARMACY)
DEPARTMENT OF
PHARMACEUTICS
VIKAS COLLEGE OF
PHARMACY
VISSANNAPETA
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UNDER THE GUIDENCE OF

DR. SUBRANSHU PANDA
PRINCIPAL AND
PROFESSOR
DEPARTMENT OF
PHARMACEUTICS
VIKAS COLLEGE OF
PHARMACY
1
VISSANNAPETA

CONTENT
SCOPE AND OBJECT
INTRODUCTION

LITERATURE
DRUG PROFILE

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OBJECTIVE
My aim is formulation of combination of oral

dosage form of lamivudine and cobicistat for a

synergistic effect for hepatitis B to overcome
the toxicity of drug and at the same time to
decrease the dose of drug.
It helps to minimize the cost and maximize
the effectiveness.

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INTRODUCTION

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SYNERGISTIC EFFECT
A Drug interaction is a situation in which a

substance(usually another drug) affects the

activity of a drug when both are administered
together.
This action can be synergistic(when the drug
effect is increased) or antagonistic(when the
drugs effect is decreased) or a new effect can
be produced that neither produces on its own.

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The interaction of the two drugs may also

increase the risk of that side effects may occur.

EX: 1.Codeine with paracetamol to increase it
analgesic effect.
2.Clavulanic acid with amoxicillin in order to over
come bacterial resistance to the antibiotic.
Synergistic combination of two or more agents
can over come toxicity and other side effects
associated with high doses of single drugs by
either countering biological compensation sparing
doses on each compound.
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Hepatitis B virus

Hepatitis B is an infectious disease caused by the hepatitis

B virus which affects the liver.

It can cause both acute and chronic infections.
ACUTE: Yellow skin, dark urine
CHRONIC: Cirrosis, liver cancer and hepato cellular
carcinoma.
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STRUCTURE OF HBV

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MECHANISM OF ACTION
HBV primarily interferes with the functions of

the liver by replication in liver cells known as

hepatocytes.
Functional receptor is NTCP
Cytotoxic T lymphocytes eliminates HBV
infection by killing infected cells and
producing antiviral cytokinins which are then
used to purge HBV from viable hepatocytes.

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VIRUS TRANSMISSION
PARENTERAL
PARINATAL
SEXUAL

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CONCENTRATION OF HBV IN
VARIOUS BODY FLUIDS
HIGH: Blood, Serum, Wound exudates.
MODERATE: Semen, Vaginal fluid, Saliva.
LOW/NOT DETECTABLE: Urine, feces, sweat,

tears

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and breast milk.

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PREVENTION
By Vaccination since 1982.
Over 750,000 people die of HB each year.
Research is looking to create foods that

contain HBV Vaccine.

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LITERATURE

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LITERATURE

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DRUG PROFILE
LAMIVUDINE
BCS CLASS : Class III drug
CATEGORY: Antiviral(nucleoside reverse transcriptase

inhibitor)
PHYSICOCHEMICAL PARAMETERS
SOLUBILITY: 70mg/ml in water.
DESCRIPTION:

white to off white crystalline solid.

MOL.WT: 229.26 g/mol.
MOL.FORMULA: C8H11N3O3S
MELTING POINT:
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160-162C
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PHARMACOKINETIC PARAMETERS

Bio availablity: 82-88%

Protein binding: less than 36%
Half life: 5-7 yrs
Vd: aprox.1.3L/Kg
Excretion: Renal
Route: oral
Dose: Tablet: 100mg
solution: 5mg/ml
Brand name: Epivir HBV
Storage: Tablet: 59-86 degrees F
Solution: 68-77 degrees F.
METOBOLISM: Metabolised by CYP 450 3A4 enzyme.

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COBICISTAT
PHYSICOCHEMICAL PARAMETERS
CATEGORY: PHARMACO ENHANCER
SOLUBILITY: Insoluble in water, soluble in 0.1N HCL, PH 1.9
Freely soluble in methanol.
DESCRIPTION: Hydroscopic amorphous solid.
MOL.WT:
776.0347 g/mol
MOL.FORMULA: C40H53N7O5S2
PHARMACOKINETIC PARAMETERS
PROTEIN BINDING: 97-98%

HALF LIFE:
3.5hrs
Vd:
77 L
EXCRETION: FECES(86%), RENAL( Lesser than 10%)
ROUTE; ORAL
DOSE: 150 mg
BRAND NAME: TYBOST
STORAGE: At 25 degree C at original containers.
METOBOLISM: Extensively metabolized via CYP3A4 and 2D6 (minor).
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MECHANISM
LAMIVUDINE :It is a nucleoside reverse transcriptase inhibitor.
Have an activity against HIV I and HBV through inhibition
of reverse transcriptase activity.(DNA chain termination).
The lack of a 3-OH group in the incorporated nucleoside
analogue prevents the formation of the 5-3 phosphodi
ester linkage essential for DNA chain elongation and
there fore the viral DNA growth is terminated.
The drug block the RT enzyme. This enzyme changes
HIVs genetic material(RNA) to the form of DNA.

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The lamivudine in EPIVIR-HBV can reduce the ability of the hepatitis

B virus to multiply and infect new liver cells. It may help to lower the
amount of hepatitis B virus in your body.
EPIVIR-HBV does not cure chronic hepatitis B and does not reduce
the risk of spreading hepatitis B to others.

EPIVIR-HBV is the brand name of a product that contains lamivudine,

a drug used to treat chronic hepatitis B in patients with actively
growing virus and liver inflammation. Hepatitis B can cause damage
to cells in the liver. Eventually, this can scar the liver.
The lamivudine in EPIVIR-HBV can reduce the ability of the hepatitis
B virus to multiply and infect new liver cells. It may help to lower the
amount of hepatitis B virus in your body. EPIVIR-HBV contains a lower
dose of lamivudine than the dose in EPIVIR, COMBIVIR, and
TRIZIVIR.
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COBICISTAT :That has no activity against HIV or HBV.

It has an ability to inhibit CYP450 3A4 enzyme has been
used to enhance the activity of other anti viral agents.
This can reduce the cost of antiviral therapy, reduce pill
burden for patients, development of resistance and
enhance adherence to antiviral therapy.

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REFERENCES
Murthy, Robert L; and Sanne. dose ranging,

randomized, clinical trail of atazanavir with

lamivudine and stavudine in antiretroviral
nave subjects: 48 weeks results. AIDS: 5
December 2003-volume 17-Issue 18-pp26032614.
M.Rangapriya: Validation of u.v spectroscopy
for simultaneous estimation of stavudine,
lamivudine, and nevirapine in tablet
formulations. International journal of
pharmaceutical sciences and Research. Vol 5
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No 10 oct 2014.

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