RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA.
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR M.PHARM
SOLAPURE RAMEEJRAJA R
Shivaji nagar; Azad Galli No 4,
Name of the candidate NIPANI. Tq - Chikodi.
And address. Dist- Belgaum- 591237
RRKS’s College of Pharmacy,
2. Name of Institution
Naubad, Bidar-585 402
3. Course of study and subject.
Date of admission to the
FORMULATION AND EVALUATION OF
5. Title of Topic SELF EMULSIFYING DRUG DELIVERY
SYSTEM OF SIMVASTATIN.
6. BRIEF RESUME OF THE INTENDED WORK:
6.1. Need for the study:
Self-emulsifying drug delivery systems (SEDDSs) have gained exposure for their
ability to increase solubility and bioavailability of poorly soluble drugs. SEDDSs are isotropic
mixtures of oils and surfactants, sometimes containing cosolvents, and can be used for the
design of formulations in order to improve the oral absorption of highly lipophilic compounds.
SEDDSs emulsify spontaneously to produce fine oil-in-water emulsions when introduced into
an aqueous phase under gentle agitation. SEDDS can be orally administered in soft or hard
gelatin capsules and form fine, relatively stable oil-in-water emulsions upon aqueous dilution.1
In recent years, the formulation of poorly soluble compounds presented interesting
challenges for formulation scientists in the pharmaceutical industry. Up to 40% of new
chemical entities discovered by the pharmaceutical industry are poorly soluble or lipophilic
compounds, which leads to poor oral bioavailability, high intra- and inter-subject variability,
and lack of dose proportionality.1
In the oral formulation of such compounds, a number of attempts such as decreasing
particle size, use of wetting agents, coprecipitation, and preparation of solid dispersions— have
been made to modify the dissolution profile and thereby improve the absorption rate. Recently,
much attention has focused on lipid-based formulations to improve the bioavailability of
poorly water soluble drugs. Among many such delivery options, like incorporation of drugs in
oils , surfactant dispersion , emulsions and liposomes , one of the most popular approaches are
the self-emulsifying drug delivery systems (SEDDSs).1
Simvastatin is a cholesterol-lowering agent widely used to treat hypercholesterolemia.
Simvastatin is a crystalline powder with a melting point of 135-138˚c, is practically insoluble
in water and poorly absorbed from the gastro-intestinal tract.2
The objectives of this study will be to develop to enhance the solubility and improving
bioavailability of SEDDS of simvastatin to administer them through oral route resulting in
increasing their clinical efficacy.
6.2 Review of literature
Literature review shows that no work has been published on the Self-emulsifying drug
delivery systems of Simvastatin.
1. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10 (CoQ10), using
polyglycolyzed glycerides (PGG) as emulsifiers and to evaluate their bioavailability in
dogs. Four types of self-emulsifying formulations were prepared using two oils
(Myvacet 9-45 and Captex-200), two emulsifiers (Labrafac CM-10 and Labrasol) and a
cosurfactant (lauroglycol). In all the formulations, the level of CoQ10 was fixed at
5.66% w/w of the vehicle. The data suggest the potential use of SEDDS to provide an
efficient way of improving oral absorption of lipophilic drugs.3
2. Phenytoin were successfully formulated as a stable SEDDS formulation that showed
significantly improved invitro release of phenytoin when compared to a commercially
available phenytoin suspension.4
3. Studies have confirmed that Solid SEDDS substantially improved solubility /
dissolution, absorption and bioavailability of poorly water-soluble drugs. As
improvements or alternatives of conventional liquid SEDDS, S-SEDDS are superior in
reducing production cost, simplifying industrial manufacture, and improving stability
as well as patient compliance.5
4. In this study, the dynamics of powder flow upon griseofulvin self-emulsified drug
delivery system (SEDDS) addition to silica and silicates and the effect of these
adsorbents on drug release were investigated. SEDDS was adsorbed at SEDDS /
adsorbent ratios from 0.25:1 to 3:1 on magnesium aluminum silicate [5 and 80 µm],
calcium silicate [25µm], and silicon dioxide [3.6, 20, and 300µm]. Dissolution of drug
from adsorbed-SEDDS was found to be dependent on pore length and nucleation at the
lipid/adsorbent interface. Increase in dissolution rate was observed with an increase in
surface area and was independent of the chemical nature of the adsorbents.6
5. Development of a newpellet based self-emulsifying (SE) drug delivery system for the
oral delivery of poorly soluble drugs. Lipid mixtures composed of Solutol® HS 15 and
medium chain glycerides were optimized with respect to their self-emulsifying
properties. The liquid SE lipid was mixed with microcrystalline cellulose and
transformed into pellets by extrusion/spheronization. The pellets were characterized for
size, shape, surface characteristics and friability. In vitro dissolution and digestion
experiments were carried out using physiological dissolution media. Extrusion /
spheronization are a suitable process to produce solid selfemulsifying pellets with up to
40% load of a liquid SE mixture. Digestion induces a change in lipid composition
which affects the solubilization capacity of the lipid phase.7
6. The solid SEDDS of dexibuprofen were prepared by spray drying, using water-
insoluble Aerosil 200 as a solid carrier.The solid SEDDS consisted of well-separated
particles with smooth surface and preserved the self-emulsification performance of the
liquid SEDDS. Both DSC measurements and X-ray diffraction analysis suggested that
dexibuprofen in the solid SEDDS may be in the molecular dispersion state. In vitro
dissolution test showed that the solid SEDDS had a faster in vitro release rate than the
powder. This solid self-emulsifying system may provide a useful oral solid dosage form
for poorly water-soluble drug, dexibuprofen.8
7. Self-emulsifying formulation of Itraconazole was developed in this study, shows
constant absorption after oral administration with no effect of dietary condition. Since
SEDDS rapidly formed fine particles sized 100–1000 nm, the dissolution problems
were solved and the absorption was improved. There was no need of bile salts for
SEDDS that formed microemulsion in the stomach, because the formulation was
sufficiently solubilized of itself. SEDDS might be a useful system for itraconazole
which shows much higher absorption and less affected by food intake.9
8. A new SEDDS & SMEDDS have been developed to increase the solubility, dissolution
rate and oral bioavailability of a poorly water soluble drug Carvedilol. The in vitro
dissolution rate of carvedilol from SEDDS & SMEDDS shows more than two-fold
faster compared with that from tablets.10
7. MATERIALS AND METHOD
7.1 Source of data:
R.G.U.H.S. Library, Bangalore.
International pharmaceutical abstract.
I. Methods for the preparation of SEDDS of Simvastatin:
a. Simvastatin dissolve in appropriate amount of ethanol.
b. Pluronic-f-68 dissolve in ethanol.
c. Simvastatin solution added to pluronic-f-68 solution.
d. Then appropriate amount of PEG-200 will be added to Tween-80 and mixed
properly by stirring with a glass rod.
e. Then the mixture of Tween-80 and PEG-200 will be added to the drug-ethanol
solution and mixed by stirring.
II. Evaluation of SEDDS of Simvastatin:
a. Solubility study of drug: The solubility of simvastatin in various oil,
surfactant, and co-surfactant will be determined respectively. The
concentration of simvastatin will be determined by UV-spectrophotometer.11
b. Particle size analysis: The particle size and size distribution of different
formulation will be determined with dynamic light scattering DLS.
c. Determination of the drug content: The dispersed systems of simvastatin
will be assayed spectrophotometrically for the drug content at the wavelength
d. Stability studies: Accelerated stability studies will be carried out as per ICH
e. FTIR study: IR spectroscopy is one of the important analytical techniques
for chemical identification. The drug polymer interaction will be studied by
7.3 Does the study require any investigation or intervention to be conducted on
patients or other humans or animals? (If so please describe briefly)
-------------- Not under the plan of work -------------
7.4 Has ethical clearance been obtained from your institution in case of 7.3.
-------------- Not applicable -------------
8. LIST OF REFERENCES
1. Ritesh B. Patel, Rakesh P. Patel, Madhabhai M. Patel. Self-Emulsifying Drug Delivery
Systems, Pharmaceutical Technology, Page: 1-5.
2. Martindale, The complete drug reference, 34 editions, Page 997.
3. T.R. Kommuru, B. Gurley, M.A. Khan, I.K. Reddy; Self-emulsifying drug delivery
systems (SEDDS) of coenzyme Q10: formulation development and bioavailability
assessment; International Journal of Pharmaceutics 212 (2001) 233–246.
4. Eman Atef, Albert A. Belmonte; Formulation and in vitro and in vivo characterization
of a phenytoin self-emulsifying drug delivery system (SEDDS); European journal of
pharmaceutical sciences 35(2008) 257–263.
5. Bo Tang, Gang Cheng, Jian-Chun Gu and Cai-Hong Xu; Devolopment of solid self-
emulsifying drug delivery systems: preparation techniques and dosage forms, Drug
Discovery Today. Volume 13, Numbers 13/14, July 2008, Page: 606-611.
6. Vikas Agarwal, Akhtar Siddiqui, Hazem Ali, Sami Nazzal; Dissolution and powder
flow characterization of solid self-emulsified drug delivery system (SEDDS),
International Journal of Pharmaceutics 366 (2009) 44–52.
7. Ahmed Abdalla, Sandra Klein, Karsten Mader; A new self-emulsifying drug delivery
system (SEDDS) for poorly soluble drugs: Characterization, dissolution, in
vitrodigestion and incorporation into solid pellets, European journal of pharmaceutical
sciences 35( 2008) 457–464.
8. Prabagar Balakrishnan et.al ; Enhanced oral bioavailability of dexibuprofen by a novel
solid Self-emulsifying drug delivery system (SEDDS), European Journal of
Pharmaceutics and Biopharmaceutics 72 (2009) 539–545.
9. Ji-Yeon Hong, Jin-Ki Kim et.al; A new self-emulsifying formulation of itraconazole
with improved dissolution and oral absorption, Journal of Controlled Release 110
(2006) 332 – 338.
10. Lanlan Wei, Peinan Sun, shufang Nie, Weisan Pan. Preparation and Evaluation of
SEDDS and SMEDDS Containing Carvedilol. Drug Development and Industrial
Pharmacy, Vol. 31 Issue 8, Sept, 2005, Pages 785-794.
11. Nilesh jain, Ruchi jain, Hemant Swami, et al. Spectrophotometric Method for
simultaneous Estimation of Simvastatin and Ezetimibe in bulk drug and its combined
dosage form. Int. J. Pharmacy and Pharmaceutical Sciences. Vol. 1 Issue 1. 2009. Page
9. Signature of the candidate
SOLAPURE RAMEEJRAJA R
Remarks of the Guide Self-emulsifying drug delivery systems
10. (SEDDS) of Simvastatin definitely
enhanced the solubility and
11. Name and Designation of
(in block letters)
MOHAMMED. MAJID IQBAL
Dept. of Pharmaceutics
RRK’S College of Pharmacy
Naubad, BIDAR - 585402
12. Name and Designation
(In block letters)
12.1 Co – Guide ------------
12.2 Signature ------------
13. 13.1 Remarks of the Chairman and
DR. K SREENIVASA RAO