This document outlines a research plan for developing and evaluating a Glipizide loaded transdermal film. The objectives are to conduct preformulation studies, compatibility studies using FTIR, reduce drug particle size using precipitation, characterize drug particle size using SEM, formulate films using solvent evaporation, and evaluate films for properties like drug content and in-vitro drug release. The need is to improve Glipizide's solubility, dissolution, and bioavailability through the transdermal route to reduce side effects. The plan involves literature review, material selection, preformulation tests, film formulation, evaluation, kinetic modeling, and reporting.

1. 1
Supervisior : Dr. G. Gnanarajan
(Associate professor)
Name:-Prinsy Rana
M.Pharm
(pharmaceutics)-2nd yr

2. 2
S.NO. TOPIC
1 INTRODUCTION
2 LITERATURE REVIEW
3 AIMS AND OBJECTIVE
4 RESEARCH PLAN
5 NEED FOR THE STUDY
6 PROGRESS REPORT
7 REFERENCE
CONTENTS

3. INTRODUCTION
 Transdermal drug delivery systems (TDDS) are defined as
self-contained, discrete dosage forms, when applied to
intact skin, deliver the drug(s), through the skin, at a
controlled rate to systemic circulation.
 Transdermal drug delivery systems (TDDS), also known
as “patches,” are dosage forms designed to deliver a
therapeutically effective amount of drug across a patient’s
skin.
 TDDS offer many advantages, such as elimination of first
pass metabolism, sustained drug delivery, reduced
frequency of administration, reduced side effects and
improved patient compliance
3

4.  The Transdermal route of administration is recognized as
one of the potential route for the local and systemic
delivery of drugs. In comparison to conventional
pharmaceutical dosage forms.
4

5. Advantages of Transdermal Drug Delivery System
(TDDS)
• Avoidance of first pass metabolism of drugs.
• Reduced plasma concentration levels of drugs.
• Improved bioavailability.
• Easy elimination of drug delivery in case of toxicity.
• Reduces daily dosing, thus, improving patient compliance.
5

6. LITERATURE REVIEW
 P.Srikanth Reddy et al (2014),Formulated and evaluated
transdermal patches of perindropril solvent casting technique using
hydroxypropylmethylcellulose, eudragit RL 100, sodium
carboxymethylcellulose and carbopol 934P as polymers. Propylene
glycol and DMSO were used as plasticizer and penetration enhancer
respectively. Ethanol, methanol and dichloromethane were used as
solvents & Good results were obtained.
 KV. Vilegave et al (2012), formulated, characterized and
evaluated transdermal patches of carvedilol with different ratio
of hydrophilic (eudragit RL 100, HPMC) and hydrophobic
(eudragit RS 100, cellulose) combinations plasticizers by solvent
evaporating technique, developed transdermal patches increase
the efficacy of carvedilol.
6

7.  Madhulatha A et al (2013), formulated and evaluated
transdermal patches of ibuprofen containing ibuprofen with
different ratio of chitosan , HPMC and combination of
chitosan-HPMC by solvent evaporating technique and
concluded that, chitosan/HPMC (75;25) with 30% plasticizer
may be suitable for development of transdermal drug delivery
system of ibuprofen.
 Vandana Mohabe et al (2011), Transdermal matrix patches
of captopril were prepared by casting method employing
different ratios of polyvinyl alcohol, ethyl cellulose, polyvinyl
pyrrolidone and hydroxypropyl methylcellulose concluded
that span 80 were better suited with n-dibutyl phthalate as
plasticizer as well as permeation enhancer for the
development of captopril transdermal patch.
7

8.  Arijit Gandhi et al (2014), developed a suitable transdermal
matrix patch of Metoprolol tartrate with different
proportions of polyvinyl pyrolidine (PVP) and chitosan
crosslinked with glutaraldehyde (GA). The control release of
drug from the transdermal patches suggested that the
frequency of administration can be reduced.
 Kunal.N Patel et al (2012), developed a matrix type
transdermal system containing drug diclofenac acid by
the solvent evaporation technique, different
concentration of labrasol, oleic acid, and triacetin were
used to enhance the transdermal permeation of
diclofenac acid. The prepared patches showed good
uniformity with regards to drug content and drug
release.
8

9.  J.R.G. Gupta et al (2009), formulated and evaluated matrix type
transdermal patches of glibenclamide using three polymer by
solvent evaporation technique poly ethylene glycol (PEG) 400 was
used as plasticizer and di methyl sulfoxide (DMSO) was used as
permeation enhancer and concluded that patches were suitable
for long period of time in single dose.
 Shahida Jannat et al (2012), Formulated and Evaluated
Sustained Release Matrix Type Transdermal Film of Ibuprofen
Transdermal films of Ibuprofen using Eudragit L 100, Kollidon SR
and their combination were separately prepared by solvent casting
method and the formulation were satisfactory.
9

10. 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
10

11.  Physiochemical Properties:
 State: Solid
 Description: white powder
 Solubility: Insoluble in water, ethanol, freely Soluble in chloroform,
dimethylformamide, Sparingly soluble in Acetone.
 Melting point: 200-2030C .
 Dosage Form strengths: initial dose 5mg , maintenance dose 5-10mg.
 Pharmacokinetic Properties:
 Absorption and bioavailability : 100% (immediate release)
: 90% (extended release)
 Drug protein binding: 98- 99%
 Peak plasma conc. : 1-3 hours
 Half life: 2 to 4 hours hours .
 Metabolism: Hepatic
 Elimination : Mean t1/2 is 2 to 4hours. Mean total CL is about 3L/h. about 80% is
excreated in urine, 10% in feces as metabolites.
11

12.  Mechanism of action: Glipizide acts by partially
blocking potassium channels among beta cells of pancreatic islets of
Langerhans. By blocking potassium channels, the cell depolarizes which
results in the opening of voltage-gated calcium channels. The resulting
calcium influx encourages insulin release from beta cells. Sulfonylureas may
also cause the decrease of serum glucagon and potentiate the action of
insulin at the extrapancreatic tissues.
 Uses: Glipizide is used with a proper diet and exercise program to control
high blood sugar in people with type 2 diabetes. It may also be used with
other diabetes medications. Controlling high blood sugar helps
prevent kidney damage, blindness, nerve problems, loss of limbs, and
sexual function problems. Proper control of diabetes may also lesser your
risk of a heart attack or stroke. It lowers blood sugar by causing the release
of your body's natural insulin.
12

13.  Side effects: Nausea, vomiting, loss of
appetite, diarrhea, constipation, upset stomach, headache,
and weight gain may occur. There are some serious side effects
including: signs of infection, easy bleeding/bruising, stomach pain,
dark urine, unusual tiredness/weakness, unusual/sudden weight gain,
mental/mood changes, swelling hands/feet, seizures.
13

14. Aim
Development and evaluation of Glipizide Loaded
Transdermal film.
Objectives :
 To conduct preformulation studies
 To conduct compatibility studies of polymer and API by FTIR.
 To reduct the particle size of drug by using precipitation
method.
 To determine size of drug by SEM.
 To formulate Glipizide loaded transdermal film by solvent
evaporating method.
 To evaluate the drug loaded films for, folding endurance,
moisture content, drug content, entrapment efficiency.
 To perform the in-vitro drug release studies for the best selected
formulation.
14

15. RESEARCH PLAN
Literature review/search
Selection of drug and polymer.
Preformulation studies of drug
Organoleptic properties
Characterization and identification of drug ( IR, Melting point)
Physicochemical properties
Drug excipient Compatibility Studies by FTIR.
Preparation of Calibration curve of the drug.
15

16. Preparation of Master formula for Transdermal Films
Formulation and Development of glipizide loaded transdermal film
Evaluation of Formulations
Physicochemical evaluation
 Thickness
 Folding endurance
 Drug content
 Flatness
 Tensile strength
 Percentage moisture content
In-vitro release evaluation
16

17. Kinetic modeling on drug release studies
Compilation of work
Thesis writing
publication
17

18. NEED FOR THE STUDY
 Glipizide is practically insoluble in water and comes under biopharmaceutical
classification system II. Thus dissolution of Glipizide is rate limiting factor. It
becomes a requirement to improve solubility of glipizide to enhance the
bioavailabity, dissolution rate & diffusion rate of drug (To enhance the
solubility of drug, particle size reduction was done by precipitation method).
 There are some side effects of glipizide such as Nausea, vomiting, loss of
appetite, diarrhea, constipation, upset stomach, headache and some serious
side effects, including: bleeding/bruising, stomach pain, dark urine, which can
be avoided by transdermal route.
 Enhance the patient compliance, long term therapy and avoiding first-pass
metabolism and increasing the uniform bioavailability of Glipizide.
 To improve the bioavailability and reduce the local and systemic side effects the
need to formulate the transdermal delivery arises.
18

19. 19

20. PREFORMULATION STUDIES
Preformulation study related to Drug
 Organoleptic properties: organoleptic properties of Glipizide were characterization
by descriptive terminology, and shown in table.
 organoleptic properties of Glipizide was observed by physical and visual method.
s.no. Properties Result
1. State Solid
2. Colour White powder
3. Odour odourless
4. Taste Bitter
20

21.  Solubility: solubility of Glipizide checked in different and result shown in
table.
s.no. Solvent Descriptive term
1. Water Insoluble
2. Methanol Slightly soluble
3. Ethanol Insoluble
4. Chloroform Freely soluble
5. Acetone Sparingly soluble
21

22.  Determination of Melting Point: the sample was loaded in to sealed capillary
(melting point capillary) which was then placed in melting point apparatus. The
sample was then heated and as the temperature increase the sample was observed to
detect the phase change from solid to liquid phase. The temperature at which the
phase changes occur gives the melting point.
 The melting point of Glipizide is 200-205ᵒc.
22

23. y = 0.0164x - 0.016
R² = 0.9931
-0.05
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0 5 10 15 20 25 30
Calibration curve of Glipizide at 7.4 PH Buffer
23
Concentration µg/ml

24. S.NO CONCENTRATION ABSORBANCE
1 0 0.000
2 5 0.061
3 10 0.126
4 15 0.229
5 20 0.317
6 25 0.399
24

25. y = 0.015x - 0.0094
R² = 0.9874
-0.05
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0 5 10 15 20 25 30
calibration curve of glipizide in 5.5 PH buffer
Calibration curve of Glipizide at 5.5 PH Buffer
25
Concentration µg/ml

26. S.NO CONCENTRATION ABSORBANCE
1 0 0
2 5 0.051
3 10 0.129
4 15 0.230
5 20 0.310
6 25 0.350
26

27. Identification of drug by FTIR:
Infrared spectrum of Glipizide was determined by using Fourier Transform Infrared
Spectrophotometer using KBr disks method. The sample (0.5 to 1.0 mg) is finely
grounded and intimately mixed with approximately 100 mg of dry potassium bromide
powder.
Drug
Name
Sample 010 By Administrator Date Wednesday, December 16 2015
Description
4000 4003500 3000 2500 2000 1500 1000 500
55
-1
5
10
15
20
25
30
35
40
45
50
cm-1
%T
2924.27cm-12854.31cm-1
1459.00cm-1
1376.65cm-1
1332.97cm-1
1527.85cm-1
1307.63cm-1
1158.14cm-1
721.99cm-1
1034.40cm-11648.42cm-1
1686.90cm-1
2725.03cm-13322.85cm-1
3247.22cm-1
3352.85cm-1 1247.24cm-1 903.99cm-1
606.18cm-11085.89cm-1
1192.80cm-1
1060.49cm-1
969.17cm-1
539.41cm-1
839.34cm-1
686.38cm-11583.55cm-1
1598.04cm-1 817.07cm-1
413.19cm-1
620.21cm-1
577.15cm-1
444.10cm-1
Fig. 1: FTIR of pure drug (glipizide) Reference Standard (I.P. 2010)
27

28.  Grinding and mixing can be done with mortar and pestle. The mixture is then
pressed into a transparent disk in an evacuable die at sufficiently high pressure.
Suitable KBr disks or pellets can often be made using a simpler device such as a
hydraulic press. The base line correction was done using dried potassium
bromide. Then, the spectrum of dried mixture of drug and potassium bromide
was scanned from 2000 cm -1 to 400 cm -1 compare with reference graph.
28

29. drug+hpmc
Name
Sample 011 By Administrator Date Wednesday, December 16 2015
Description
4000 4003500 3000 2500 2000 1500 1000 500
49
-1
0
5
10
15
20
25
30
35
40
45
cm-1
%T
2859.00cm-1 1455.70cm-1
1376.34cm-1
1158.34cm-1
1332.98cm-1
1527.92cm-1
1307.71cm-1 722.02cm-11648.76cm-1
3247.73cm-1
3323.12cm-1
2725.32cm-1
2670.56cm-1
1085.93cm-1
3352.96cm-1
1247.26cm-1
606.21cm-1
903.99cm-1
1192.81cm-1
1219.56cm-1
970.09cm-1
885.20cm-1
539.49cm-1
839.38cm-1
686.37cm-1
670.50cm-11583.57cm-1
620.18cm-1
817.07cm-11598.05cm-1
577.19cm-1
413.21cm-1
631.87cm-1
444.09cm-1
Fig.2: FTIR Spectra of Glipizide with HPMC K100 (Polymer)
29

30. Drug +E S.
Name
Sample 012 By Administrator Date Wednesday, December 16 2015
Description
4000 4003500 3000 2500 2000 1500 1000 500
65
-1
0
5
10
15
20
25
30
35
40
45
50
55
60
cm-1
%T
2922.13cm-1
2852.43cm-1
1455.98cm-1
1376.56cm-1
1333.18cm-1
1158.43cm-11527.86cm-1
722.05cm-1
1687.77cm-1
1034.28cm-11648.87cm-1
2725.25cm-1
2670.56cm-13247.43cm-1
3322.85cm-1
1247.25cm-1
903.89cm-1
3352.78cm-1 1192.85cm-1 606.15cm-1
1085.94cm-1
1219.83cm-1
1060.46cm-1
885.03cm-1
969.03cm-1
539.44cm-1839.44cm-1
686.41cm-1
1583.49cm-1
1597.96cm-1 817.07cm-1
413.15cm-1
620.23cm-1
577.09cm-1
444.03cm-1
Fig.3: FTIR Spectra of Glipizide and Eudragit S100 (Polymer)
30

31. Drug+E L
Name
Sample 013 By Administrator Date Wednesday, December 16 2015
Description
4000 4003500 3000 2500 2000 1500 1000 500
55
-1
0
5
10
15
20
25
30
35
40
45
50
cm-1
%T
2859.50cm-1 1455.83cm-1
1376.38cm-1
1158.47cm-11528.12cm-1
1332.90cm-1
1687.88cm-1
1649.16cm-1
722.06cm-11034.46cm-1
3247.72cm-1
3322.97cm-1
2725.32cm-1
1247.32cm-1
1192.87cm-13352.86cm-1 904.03cm-1 606.27cm-1
1086.17cm-1
1060.56cm-1
968.47cm-1
884.99cm-1 539.50cm-1
839.39cm-1
686.46cm-1
1583.68cm-1
1598.16cm-1
817.13cm-1
413.19cm-1
620.21cm-1
577.22cm-1
444.08cm-1
Fig.4: FTIR Spectra of Glipizide and Eudragit L100(Polymer)
31

32. Size Reduction of Glipizide by Precipitation Method
In precipitation technique the drug is dissolved in a solvent, which is then
added to antisolvent to precipitate the crystals. The basic advantage of
precipitation technique is the use of simple and low cost equipments; The
limitation of this precipitation technique is that the drug needs to be soluble in
at least one solvent and this solvent needs to be miscible with antisolvent.
 Acetone was used as solvent and distilled water was used as a anti solvent.
METHODOLOGY
32

33. % Yield of drug after size reduction
Drug taken – 1000 mg
Actual yield – 785 mg
% yield = actual yield / theortical yield * 100
785/1000 * 100 = 78.5%
33

34. SEM OF GLIPIZIDE
34

35. 35

36. 36

37. Formulation of Glipizide loaded
transdermal film
The various formulations of Transdermal film were prepared by solvent
casting method. For formulations, different polymers was taken in mortar
pestle and triturated properly for the fine powder after that 25 mg of drug
(Glipizide) was added then 10ml chloroform & 10 ml methanol was added &
triturated properly in uniform direction. After that magnetic stirring was done
for 45 minutes. After that the mixture was uniformly spreaded on a petri-dish
and dried at room temperature. Transdermal film was obtained, glycerol was
used as plasticizer & PEG was used as penitration enhancer.
37

38. 38
S.No. Batch
Code
HPMC Eudragit
S100
Eudragit
L100
Ethyl
cellulose
drug Glycerol PEG
400
CHLOROFORM
: METHANOL
1. F1 250 _ _ _ 25 1 0.5 1:1
2. F2 _ 350 _ _ 25 1 0.5 1:1
3. F3 _ _ 350 _ 25 1 0.5 1:1
4. F4 _ _ _ 250 25 1 0.5 1:1
5. F5 125 _ _ 125 25 1 0.5 1:1
6. F6 _ 200 200 - 25 1 0.5 1:1
7. F7 _ 200 125 25 1 0.5 1:1
FORMULATION

39. REFERENCES
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Development of Transdermal Patches for Perindopril, Research Journal of
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 KV. Vilegave, SP. Hiremath, PM. Chandankar, MS. Sanap, VT. Sathe, AV. Patil and M.
Kharjul, Formulation, Characterization and Evaluation (In vivo-Invitro study) of Matrix
Type Transdermal Patches of Carvedilol, International Journal of Research In Pharmacy
and Chemistry, 2012, 2(3), 2231-2781.
 Madhulatha A and Naga Ravikiran, Formulation and Evaluation of Ibuporfen
Transdermal Patches, International Journal of Research in Pharmaceutical and
Biomedical Sciences, 2013, Vol. 4 (1), 2229-3701.
 Arijit Gandhi, Sougata Jana, Abhijit Paul, Subrata Sheet, Rahul Nag, Kalyan Kumar
Sen, Metoprolol tartrate Containing Glutaraldehyde Cross-linked Chitosan- Polyvinyl
pyrrolidone Matrix Transdermal Patch: Preparation and Characterization, Journal of
PharmaSciTech, 2014 Vol 3 (2), 2231-3788.
39

40.  Kunal N Patel, Hetal K Patel, Vishnu A Patel, Formulation and Characterization of
Drug in adhesive Transdermal Patches of Diclofenac acid, International Journal of
Pharmacy and Pharmaceutical Sciences, 2012, Vol 4, Issue 1, 0975-1491.
 Vandana Mohabe, Rachna Akhand and Anupam Kumar Pathak, Preparation And
Evaluation of Captropril Transdermal Patches, Bulletin of Pharmaceutical Research,
2011;1(2):47-52, 2249-9245.
 Shahida Jannat, Md. Abdullah A Masum, Florida Sharmin, S M Ashraful Islam and
Md. Selim Reza, Formulation and Evaluation of Sustained Release Matrix Type
Transdermal Film of Ibuprofen, Bangladesh Pharmaceutical Journal, 2012, 15(1):
17-21.
 Mohd. Amjad, Mohd. Ehtheshamuddin, S. Chand1, Hanifa1, M. Sabreesh1, R.
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– 0744.
 Rajesh Asija, Avinash Gupta and Bhagwan Swaroop Maheshwari, Formulation and
evaluation of Transdermal patches of Torasemide, International Journal of Advances
in Scientific Research 2015; 1(01): 38-44, 2395-3616.
40

41.  Shailesh T. Prajapati, Charmi G. Patel, and Chhagan N. Patel, Formulation and
Evaluation of Transdermal Patch of Repaglinide, International Scholarly Research
Network, 2011, 651909.
 Kevin C. Garala, Anil J. Shinde, Pratik H. Shah, Formulation and in-vitro
Characterization of Monolithic Matrix Transdermal System using
HPMC/EUDRAGIT S 100 Polymer Blends, International Journal of Pharmacy and
Pharmaceutical Sciences, 2009, Vol. 1(l).
 Pandya Narendra, Patel Manvi, Bhaskar V.H., Patel K.R., Development of
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Pharmaceutical Science and Bioscientific Research, 2011, Vol 1 (1), (59-64).
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Patches of Glipizide, International Journal of Pharma and Bio Sciences, 2014, 5(1),
142 – 150, 0975-6299.
41

42.  Kajal Ghosal, Rajan. R, A. Nanda, Effects of Chemical Enhancers on the Release of
Glipizide through matrix Patch, International Journal of ChemTech Research, 2009, Vol.1,
(4), 1128-1130, 0974-4290.
 Koteswararao P, Duraivel S, Sampath Kumar KP, Debjit Bhowmik, Formulation and
Evaluation of Transdermal Patches of Anti-Hypertensive Drug Metoprolol Succinate,
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43. 43