Glipizide microemulsion

1. FORMULATION AND
EVALUATION OF GLIPIZIDE
MICROEMULSION
BY SASWAT MOHANTY
ROLL NO:MP-2421
MPHARM 3rd SEM(PHARMACEUTICS)
S.P.E.R,BERHAMPUR UNIVERSITY
UNDER THE GUIDANCE OF ASST. PROFESSOR MRS. SMITA PADMA
MOHANTY

2. INTRODUCTION
• DEFINITION:-
Microemulsions are clear, thermodynamically stable isotropic liquid mixtures of oil,
water and surfactant, frequently in combination with a cosurfactant. The aqueous
phase may contain salt and/or other ingredients, and the "oil" may actually be a
complex mixture of different hydrocarbons.
During the recent decades, various colloidal systems have been investigated as
suitable pharmaceutical vehicles for oral delivery of the active substance.
Microemulsions are thermodynamically stable isotropically clear systems in which
two immiscible liquids (i.e., water and oil) are mixed to form a single phase with an
appropriate surfactant or its mixture.

3. ADVANTAGES AND DISADVANTAGES OF
MICROEMULSION
• ADVANTAGES:-
These are thermodynamically stable.
Require minimum energy for formation.
Easy manufacturing.
Improve drug solubilization and bioavailability.
Wide application in colloidal drug delivery system
• Disadvantages:-
Use of a large concentration of surfactant and co-surfactants.
Limited solubilizing capacity for high melting substances.
Microemulsion stability is influenced by environmental parameters such as
temperature and ph.

4. DRUG (GLIPIZIDE)
Glipizide, a second generation sulfonylurea, is used for patients with non-insulin
dependent diabetes mellitus who have failed diet and exercise therapy.
It’s bioavailability is 100%(regular formulation)and 90%(extended release).
It is a sparingly water-soluble drug with a solubility of 37.2 mg/l.
Elimination half life is 2 to 5 hrs.
Melting point is 208 to 209 °C.

5. PSEUDO TERNARY PHASE DIAGRAM
• A pseudo ternary phase diagram was constructed to determine the composition of the aqueous
phase, oil phase, and surfactant: a cosurfactant phase that will yield a microemulsion. Among
the various phases formed by these four components a field with clear and transparent liquid
microemulsions was identified.

6. METHOD OF PREPARATION

7. AIM AND OBJECTIVE
To delivery of hydroohillic as well as lipophilic drug as drug carriers because of it’s
1. Improved drug solubilization capacity- it increases the solubility by dissolving compounds
with low water solubility into an oil phase.
2. Long shelf life
3. Ease of preparation
4. Improvement of bioavailability- They can also enhance oral bioavailability by reducing the
droplet size (< 100 nm), and hence increase the rate of absorption due to surfactant-
induced permeability changes.

8. LITERATURE REVIEW
Sl.no Abstract Title Vol/page/y
ear
Remarks
1) Pain is a global crisis and significant efforts have gone
into the development of drugs that can be used to treat
pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are
a class of analgesics that act to selectively relieve pain
and inflammation without significantly altering
consciousness. Although there have been many
advancements with NSAIDs drug development; these
drugs still present with severe adverse effects and
toxicities, which often limits their use in many patients.
Moreover, others are inadequate in relieving specific
types of pain such as localized or nerve pain because of
poor systemic absorption with conventional delivery
systems.
Microemulsio
ns as
transdermal
drug delivery
systems for
nonsteroidal
anti-
inflammatory
drugs
(NSAIDs)
45/ 1849-
1855/2019
This review focuses on
the recent use of
microemulsions as a
probable solution to the
challenges of transdermal
drug delivery of NSAIDs
and how microemulsions
may be used to enhance
the development of more
effective but safer
analgesic drug products for
patients.

9. LITERATURE REVIEW
Sl.no Title Abstract Vol/page/year Remarks
2)
Potential Use of
Microbial Surfactant
in Microemulsion
Drug Delivery
System: A Systematic
Review
Microemulsions drug delivery systems
(MDDS) have been known to increase the
bioavailability of hydrophobic drugs. The
main challenge of the MDDS is the
development of an effective and safe
system for drug carriage and delivery.
Biosurfactants are preferred surface-
active molecules because of their lower
toxicity and safe characteristics when
compared to synthetic surfactants.
Glycolipid and lipopeptide are the most
common biosurfactants that were tested
for MDDS. The main goal of the present
systematic review was to estimate the
available evidence on the role of
biosurfactant in the development of
MDDS.
14/541-
550/2020
The main goal of the
present systematic
review was to estimate
the available evidence
on the role of
biosurfactant in the
development of MDDS.

10. LITERATURE REVIEW
Sl.no Title Abstract Vol/pages/ye
ar
Remarks
3) Microemulsion-based media as
novel drug delivery systems
Microemulsions are clear,
stable, isotropic mixtures of oil,
water and surfactant,
frequently in combination with
a cosurfactant. These systems
are currently of interest to the
pharmaceutical scientist
because of their considerable
potential to act as drug delivery
vehicles by incorporating a
wide range of drug molecules.
In order to appreciate the
potential of microemulsions as
delivery vehicles, this review
gives an overview of the
formation and phase behaviour
and characterization of
microemulsions.
45/89-
121/2000
The use of
microemulsions
and closely related
microemulsion-
based systems as
drug delivery
vehicles is
reviewed, with
particular
emphasis being
placed on recent
developments and
future directions.

11. PLAN OF WORK
Identification of
drug
Literature
search(books,jouranals
and internet)
Construction of pseudo
ternarnary phase
diagram
Method of preparation

12. Formulaion
Evaluation
Invitro studies
Drug profile

13. PROPOSED METHOD OF FORMULATION OF
GLIPIZIDE MICROEMULSION
 Microemulsions will be prepare by cosurfactant titration method.
 In this method about 2.5 mg of glipizide for 5 ml formulation will be accurately weigh and shall be
taken in a beaker.
 It will dissolve in an appropriate amount of oil.
 To this require amount of surfactant and water will be added.
 The preparation will be gently stirred with a mechanical stirrer until all the components are mixed
properly.
 Cosurfactant will be then added dropwise to this preparation until the solution is clear. The samples
are then stirred for 15 min to allow equilibration.

14. EVALUATION OF GLIPIZIDE MICROEMULSION
• Conductivity measurements
The electrical conductivity of the samples was measured using a Digital pH/conductivity
meter. Conductivity was measured by using 0.01N sodium chloride solution instead of using
water. The measurements were performed in triplicate at 25 °C.
• pH determination
The pH values of the samples were measured by a Digital pH meter at 37±1 °C.
• Centrifugation
In order to eliminate metastable systems, the selected drug-loaded microemulsions were
centrifuged at 4000 rpm for 4 h.
• Percent transmittance
The percent transmittance of the system was measured using UVVisible double beam
spectrophotometer (model-2201, Systronics) at 560 nm using distilled water as a blank.

15. • Rheological studies
The viscosity of the samples was measured using Brookfield Viscometer LVDV-II+P fitted with an
S-32 spindle. A Sample volume of 15 ml was used. All the microemulsions studied were subjected
to shear stress of 0-20 Pa at different rpm (3, 6, 12, 30 and 60) and the rheological behavior of the
disperse systems were examined by constructing rheograms of shear stress vs. shear rate.
• Particle size, Polydispersity index and Zeta potential measurement
Measurements were made on a Zetasizer Nano ZS instrument at 25 °C at a wavelength of 633 nm
and incorporate non-invasive backscatter optics (NIBS). At a detection angle of 173 °C
measurements were made.
• Stability studies of optimized formulation
Stability studies were carried out for optimized formulation for 6 mo at 37±2 °C and 04±2 °C
according to ICH guideline in a controlled chamber. The sample was analyzed periodically for
physical appearance, rheological properties, pH and percentage release by UV-Visible
spectrophotometer at 276 nm.

16. • Differential scanning calorimetry measurements (DSC)
DSC measurements were performed with DSC TA Q100 instrument equipped with a refrigerated cooling
system. Nitrogen with a flow rate of 50 ml/min was used as purge gas. Approximately 4 to 13 mg of sample
was weighed precisely into hermetic aluminum pans. An empty hermetically sealed pan was used as a
reference. Samples were cooled from 25 oC to −50 oC at a cooling rate of 5 oC/min, held for 3 min at −50 oC
and then heated to 25 °C at a heating rate of 10 o Stability studies of optimized formulation C/min. All
measurements were performed in triplicate.
• In vitro drug release studies
Dialysis tube method was used for performing the dissolution process. In this method, a boiling tube was
taken which was opened at both the ends. To this tube, a cellophane membrane was attached at one end,
which was previously soaked in 7.4 pH buffer for 24 h. 5 ml of microemulsion was taken from the other end
of the tube. This setup was attached to the paddle of the dissolution apparatus. The dissolution medium
consisted of 50 ml of freshly prepared phosphate buffer of pH 7.4. The release study was performed at 37±0.5
o pH determination C, with a rotation speed of 50 rpm. Samples of 3 ml were withdrawn at 1, 2, 3 up to 8 h
at regular one-hour intervals and replaced with fresh medium. Dissolution of placebo microemulsion was
performed in the same manner and samples were utilized as blank for the respective drug loaded
microemulsion. The samples were analyzed by UV-Visible spectrophotometer at 276 nm.

17. DRUG PROFILE
• DRUG:- Glipizide
• IUPAC NAME:- N-(4-[N-(cyclohexylcarbamoyl)sulfamoyl]phenethyl)-5- methylpyrazine-2-
carboxamide
• CHEMICAL FORMULA:-C21H27N5O4S
• Mol. Wt:- 445.536 g/mol
• STRUCTURE:-
• CATEGORY:-Oral hypoglycemic agent
• STORAGE:-Store At Room Temperature

18. REFERENCES
 Ljiljana Djordjevic, Marija Primorac, Mirjana Stupar. In vitro release of diclofenac
diethylamine from caprylocaproyl macrogol glycerides based microemulsions. Int J Pharm
2005;296:73-9.
 Trotta M, Morel S, Gasco MR. Effect of oil phase composition on the skin permeation of
felodipine from oil in water microemulsions. Pharmazie 1997;52:50-3.
 Bolzinger MA, Carduner TC, Poelman MC, Bicontinuous sucrose ester microemulsion: a new
vehicle for topical delivery of niflumic acid. Int J Pharm 1998;176:39-45.
 Kumar P, Mital KL. Handbook of Microemulsion: Science and Technology. Marcel Dekker,
New York, Basel; 1999.
 Kibbe AH. Handbook of Pharmaceutical Excipients. 3rd ed. Pharmaceutical Press: London;
2000.
 N Subramanium, S Ray, SK Ghosal, R Bhadra, SP Moulik. Formulation design of self-micro
emulsifying drug delivery systems for improved oral bioavailability of celecoxib. Biol Pharm
Bull 2004;27:1993–9.