EVALUATION AND FORMULATION OF

MICROSPONGES OF ATORVASTATIN

SYNOPSIS

SUBMITTED TO

UTTARAKHAND TECHNICAL
UNIVERSITY,DEHRADUN

IN THE PARTIAL FULFILLMENT

OF

BACHELOR DEGREE OF PHARMACY

BY

DIVYA BAHUGUNA

SUPERVISOR. CO-SUPERVISOR.

PROF.(DR.) ASST.PROFESSOR

Mr. VINEY CHAWLA Miss.SHIKHA YADAV

 1
CONTENT

INTRODUCTION
1

 Introduction
 Literature Survey
 Drug Profile
 Polymer Profile
 Aim and Objective
 Method
 Evaluation
 References
 Conventional topical formulations are designed to work on the outer
layers of the skin. When the active ingredients of these formulations are
released upon application, a highly concentrated layer of active
ingredient is produced that is rapidly absorbed.
Recently, there has been considerable interest in the development of
novel microsponge based drug delivery systems to achieve targeted and
sustained release of drugs (Kaity et al., 2010). Microsponges are
polymeric delivery systems consisting of porous microspheres that are
mostly used for extended topical administration of a variety of active
ingredients such as emollients, fragrances, essential oils, sunscreens, and
anti-infective, anti-fungal, and anti-inflammatory agents. Microsponges
offer many advantages such as delivering the active ingredients at
minimum dose, enhanced stability, reduced side effect and modified
drug release profile.
  Advantages of microsponges over other technologies and
delivery systems
1) Microsponges offer better control of drug release than microcapsules.
Microcapsules cannot usually control the release rate of the active
pharmaceutical ingredients (API). Once the wall is ruptured, the API
contained within the microcapsules will be released.
2) Microsponges show better chemical stability, higher payload and
easier formulation compared with liposomes.
3) In contrast to ointments, microsponges have the ability to absorb skin
secretions, therefore, reducing greasiness and shine from the skin.
Ointments are often aesthetically unappealing, greasy and sticky,
resulting in lack of patient compliance.

 Potential features of microsponge drug delivery systems

1) Microsponges show acceptable stability over pH
ranging from 1 to 11 and at high temperatures (up to 130°C).
2. Microsponges exhibit good compatibility with various vehicles and
ingredients.
3. Microsponges have high entrapment efficiency up to 50 to 60%
without drying.
 Literature Survey

 (Irit et al. (2000)

Phosphated cross-linked guar gum was prepared for colon-specific drug
delivery. Guar gum cross-linked with increasing amounts of
trisodiumtrimetaphosphate to reduce its swelling properties for use as a
vehicle in oral delivery formulations, especially drugs aimed at
localizing in the distal portions of the small bowel. Swelling of guar
gum in artificial GI fluids was reduced from 100 120- fold to 10-35-fold
depending on the amount of cross linker used.
 Lee et al.( 2000)
Organic acids like succinicacid, tartaricacid and citricacid were used as
excipients in matrix granules to modify the drug release for colon-
specific drug delivery (Nykanen et al. 1999). Amylose- Ethylcelluese
film coatings obtained from organic-based solvents were investigated as
potential vehicles for colon drug delivery. In this method amyulose-
butanol dispersion and ethycellulose in ethyllacttate/ethnol/propanol
with dibutylsebacate as plasticizer were mixed in various proportions
and coated on 5-ASA pellets to achieve desired thickness. The drug
release regulating parameters are thickness of coating and ratio of
amylose to ethylcelluese. The release of drug is irrespective of the
solvent used for coating. Formulation containing 1 part amylase and 1
part ethylcelluose of coating thickness, 15% TWG, gives desired release
profiles of 5-ASA for colon targeting.
  Fude et al. (2007)
An oral colonic drug delivery system of 5-ASA was developed using
combination of pHdependent, time-based and enzyme degradable
approaches. The pellets were coated with three functional layers i.e. the
outer EudragitL30D-55 layer for protection against GI fluids, the
intermediate layer of ethyl cellulose to inhibit the drug release during
passage through the small intestine and the inner layer of pectin for
swelling and enzyme-degradation. In vitro release studies indicated that
the coated pellets completely protected the drug release in 0.1M HCl
while the drug release was delayed for three to four hours in pH 6.8
phosphate buffer.
.
 Drug Profile

Atorvastatin (INN) marketed by Pfizer as a calcium salt under the

trade name Lipitor,is a member of the drug class known as statins,
which are used primarily for lowering blood cholesterol and for
prevention of events associated with cardiovascular disease

Atorvastatin was first synthesized in 1985 by Bruce Roth, an

alumnus of Saint Joseph's University, while he was working for the
Parke-Davis Company (since acquired by Warner-Lambert and the
Pfizer Company). Although Atorvastatin was the fifth drug in the
class of statins to be developed, clinical trials showed that
Atorvastatin caused a more dramatic reduction in LDL-C than the
other statin drugs. From 1996 to 2012 under the trade name
Lipitor, Atorvastatin became the world's best-selling drug of all
time, with more than $125 billion in sales over approximately 14.5
years.When Pfizer's patent on Lipitor expired on November 30,
2011,generic Atorvastatin became available in the United States.
Initially, Atorvastatin was manufactured only by generic
drugmakers Watson Pharmaceuticals and India's Ranbaxy
Laboratories.
 Systematic (IUPAC) name

(3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-
(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-
dihydroxyheptanoic acid

Clinical data

Trade names Lipitor,Atorva

AHFS/Drugs.com monograph

MedlinePlus a600045

Licence data US Daily Med:link

 Pregnancy cat. D (AU) X (US)

Routes Oral

Pharmacokinetic data

Bioavailability 12%

Metabolism Hepatic - CYP3A4

Half-life 14 h

Excretion Bile
 Administration:

Atorvastatin may be used in combination with bile acid sequestrants and

ezetimibe to increase the reduction in cholesterol levels. However, It is
not recommended to combine statin drug treatment with certain other
cholesterol-lowering drugs, particularly fibrates, because this may
increase the risk of myopathy-related adverse effects.

 Contraindications:

• Active liver disease: cholestasis, hepatic encephalopathy, hepatitis,

and jaundice

• Unexplained elevations in AST or ALT levels

• Pregnancy: Atrovastatin may cause fetal harm by affecting serum
cholesterol and triglyceride levels, which are essential for fetal
development.

• Breastfeeding: Small amounts of other statin drugs have been

found to pass into breast milk, although Atorvastatin has not been
studied, specifically.
 Polymer Profile

A polymer, natural or synthetic is a substance that is combined with a

drug or other active agent to release drug in a pre-designed manner1.
The development of NDDS has been made possible by the various
compatible polymers to modify the release pattern of drug2,3. Choice of
polymers always suffering from the problems of non-biocompatible,
non-biodegradable and expensive and this problem can solve with a
polymer of different properties.
Year of introduction Eudragit Grade
1954 Eudragit L 12.5
Eudragit S 12.5
1959 Eudragit E 12.5
1961 Eudragit E 100
1968 Eudragit RL 100
Eudragit RS 100
 Aim and Objective

 AIM OF THE PRESENT RESEARCH WORK:

• The present study was aimed at developing and characterizing
microsponge based, for the treatment of IBS to achieve following
objects:
• To overcome potential side effects of Aterovastatins and
enhancing their therapeutic effectiveness.
• To develop superior formulation with pronounced targeting
potential of drugs
to colon as compared to conventional delivery systems.
 PLAN OF WORK
• Exhaustive Literature survey through journals and e-journal.
• Procurement of Drug, and Excipient.
• Preformulation studies
• Preparation and optimization of microsponges.
• Development of colon specific formulation.
• In vitro and stability studies of promising formulations.
 Evaluation
 Measurement of particle size
 Morphology and Surface topography
 Production yield and entrapment efficiency
 Powder X-ray diffraction (XRD):
 In vitro release studies, release kinetics and
 mechanism
 References
1)Irit Gliko-Kabir, Boris Yagen, Abrahem Rubinstein et al. (2000)
Phosphated cross linked guar for
colon-specific drug delivery I. Preparation and physicochemical
characterization. Journal of
Controlled Release 63: 121-127.
2)Lee F.Siew, Abdul W.Basit, and Michael Newton J (2000) The
potential of organic-based
Amylose-Ethyl cellulose film coatings as oral colon-specific drug
delivery system. AAPS
PharmSciTech 1(3): 1515-1521.
3) Mohini Chaurasia, Manish K, Chourasia, Nitin K. Jain et al. (2006).
Cross-linked guar gum
microspheres; A Viable approach for improved delivery of anticancer
drugs for the treatment of
colorectal cancer. AAPS Pharm Sci Tech 7(3): E1-E9.
4) Munjeri O, Collett JH and Fell JT (1997). Hydrogel beads based on
amidated pectins for colonspecific
drug delivery: the role of Chitosan in modifying drug release. Journal of
Controlled
Release 46:273-278.