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eISSN: 2320-1428 Int.J.Inv.Pharm.Sci.

,2(1)2014;584-587
www.ijips.net

INTERNATIONAL JOURNAL OF INVENTIONS IN PHARMACEUTICAL SCIENCES

FORMULATION AND EVALUATION OF HYDROXY PROPYL METHYL CELLULOSE TRANSDERMAL DRUG DELIVERY
SYSTEMS
TEJA SRI, K. SWATHI*, K. BAVANA, P. JAYASRI DEVI, B. VIJAY KUMAR, G. SUBBA RAO
Sri Siddhartha Pharmacy College, Nuzvid- 521201, Andhrapradesh, India.

For correspondence: swathi.swass29@gmail.com Accepted On: 29th Jan 2014

ABSTRACT: Transdermal drug delivery systems of Theophylline using HPMC in different concentrations were developed by solvent casting technique
employing mercury as a substrate. Propylene glycol was used as a plasticizer. The prepared films exhibited satisfactory physico-chemical characteristics. Diffusion
studies were carried out using Franz diffusion cell. The permeation followed zero order kinetics and mechanism was found to be matrix diffusion.
Keywords: Matrix type transdermal patch, Solvent evaporation technique, Theophylline, HPMC.

INTRODUCTION: These technologies can be classified into four approaches as


Recently there has been a growing recognition that the benefits of follows: [3]
intravenous infusion can be closely duplicated without its hazards, 1. Membrane permeation controlled systems
by using the intact skin as the port of drug administration to provide 2. Adhesive dispersion type systems.
[1]
continuous drug delivery into the systemic circulation . This is 3. Matrix diffusion controlled systems.
known as the transdermal administration and the drug delivery 4. Micro reservoir type or micro sealed dissolution controlled
systems are known as transdermal therapeutic systems or systems.
popularly as transdermal patches. MATERIALS AND METHODS:
[2]
Transdermal therapeutic systems are defined as self Materials:
contained, discrete dosage forms which, when applied to the intact Teophylline was gift sample from Aurobindo Pharmaceuticals
skin, deliver the drug, through the skin at controlled rate to the (Hyderabad, India). Ethyl cellulose (EC), Propylene glycol (PG)
systemic circulation. Transdermal drug delivery systems are obtained from Vikram Thermo (India) Ltd. All the chemicals used
adhesive drug containing devices of defined surface area that deliver were of analytical grade.
a predetermined amount of drug to the surface of intact skin at a Methods:
programmed rate. These systems provide drug systemically at a Preparation of TDDS:
predictable rate and maintain the rate for extended periods of time Composition of formulation of transdermal patches was showed in
thus eliminating numerous problems associated with oral dosing Table 1. The polymeric solution (10% w/v) was prepared by
including product stability, bioavailability and the peaks and troughs dissolving HPMC in different ratios, along with drug, PG in
of pulse dosing. The structural components of transdermal devices ethanol. The solution was poured into a glass ring placed on the
include Polymer matrix or matrices, the drug, Permeation enhancers surface of liquid mercury kept in a Petri dish. The patches were
and other excipients. kept at room temperature to evaporate the solvent over night. After
Several technologies have been successfully developed to provide a complete drying of the patch aluminum foil was used as backing
rate control over the release and the transdermal permeation of film. The patches were cut to desire size and stored in desiccator
drugs. untill use [4- 6].
Table.1.Composition of Transdermal patches
S.No. Formulation Drug (mg) Polymer Solvent Plasticizer Volume of casting solvent
Code
HPMC
1 F- 1 20 20 DCM PG 10
2 F-2 20 40 DCM PG 10

Physicochemical Evaluation Thickness and Weight Variation [7- calculated.


9]
: Folding Endurance [10, 11]:
The thickness of the patches was assessed at six different points It was determined by repeatedly folding a small strip of films at the
using screw gauze and the average weight of three patches was same place till it broke. The number of times, the films could be

Page | 584
folded at the same place without breaking gave the value of folding Percent moisture absorption
endurance. Final weight Initial weight
=
[13] -------------------------------X 100
Drug Content Determination :
Initial weight
The patch (1 cm2) was cut and added to a beaker containing 100 ml Percent Moisture Loss [13]:
of phosphate buffered pH 7.4. The medium was stirred (500 rpm) This test was also carried to check the integrity of films at dry
with teflon coated magnetic bead for 5 hours. The contents were condition. Three films of 5 square centimeter area was cut out and
filtered using whatman filter paper and the filtrate was analyzed by weighed accurately and kept in a dessicator containing fused
U.V.spectrophotometer (Elico, SL-164, Hyderabad, India) at 277 anhydrous calcium chloride. After 72 hours the films were removed
nm for the drug content against the blank solution. and weighed. Average percentage moisture losses of three films
[12]
Percent Moisture Absorption : were determined shown in table 2.
The films were placed in desiccator containing saturated solution of Percent moisture loss
aluminum chloride, keeping the humidity inside the dessicator at = Initial weight Final weight
------------------------------------ X100
79.5% RH. After 3 days the films were taken and weighed the
Initial weight
percentage moisture absorption of three films were determined.
Table.2. Physicochemical Characteristics of Prepared Films
DRUG
FORMULATION MEAN MOISTURE FOLDING WEIGHT
S.NO MOISTURE CONTENT
CODE THICKNESS LOSS (%) ENDURANCE (MG)
ABSORPTION (%) (%)
1 F- 1 132 3 6.97+0.06 7.40+0.05 97.20+0.34 217 4.43 20.3 2.58
2 F-2 137 4 10.15+0.45 6.97+0.06 98.08+0.12 233 2.36 22.3 1.55

In vitro drug release studies [13,14]: compartment and it was separated from the receptor compartment
The in vitro release was carried out with the semi permeable by semipermeable membrane. The semipermeable membrane was
membrane using open ended cylinder. The cylinder consists of two previously soaked for 24 hours in phosphate buffer (pH 7.4) The
chambers, the donor and the receptor compartment. The donor receptor compartment containing 300ml phosphate buffer (pH 7.4)
compartment was open at the top and was exposed to atmosphere. in a beaker was maintained at 37 0.5 oC and stirred at 50 rpm with
The temperature was maintained at 37 0.5o C and receptor magnetic beads operated by magnetic stirrer. A sample of 1 ml was
compartment was provided with sampling port. The diffusion withdraw at predetermined time intervals and replaced with fresh
medium used was phosphate buffer (pH 7.4) .The drug containing buffer. The concentration of drug was determined by
patch with a support of backing membrane was kept in the donor spectrophotometrically at 277 nm shown in table 3.
Table.3. In-vitro drug release of Teophylline transdermal patches

TIME(H) F1 F2
0.5 16.12 14.14
1 40.23 20.23
1.5 42.32 35.15
2 44.52 40.36
3 46.56 42.56
4 50.45 48.36
5 52.78 51.56
6 60.45 53.89
7 70.46 55.45
8 77.89 60.78
9 81.23 64.45
10 85.25 70.45
11 90.36 74.78
12 94.25 80.89
Page | 585
Table.4. Release kinetics and correlation coefficient values

S.NO FORMULATION ZERO ORDER FIRST ORDER PEPPAS

r k r k r k n
1 FI 0.9982 10.2360 0.9023 -0.1234 0.9948 8.6789 0.8120
2 F2 0.9923 11.2321 0.9234 -0.2135 0.9965 9.6351 0.7452

CUMULATIVE PERCENT DRUG 100

80

60
RELEASE

F1
40
F2
20

0
0 5 10 15
TIME (Hrs)

Fig.1. Zero order release profile of transdermal patches

2.5

2
Log % drug release

1.5

1 F1
F2
0.5

0
0 0.5 1 1.5
Log time

Fig.2.Peppas plots of Transdermal patches

RESULTS AND DISCUSSION: compatible. A characteristic IR spectra of Theophylline showed at


The physicochemical characteristics of prepared patches are showed 3347 cm-1 for N-H,3060 cm-1 for C-H str, 1666 cm-1 for C-O str,
Table 2. The weights are ranged from 20.3 2.66 to 22.3 1.55mg. 1241 cm-1 for C-N str, 847 cm-1 for C-N-H, 786 cm-1 for C-H
Thickness ranged from 132 3 to 137 4 . The weights are bend, 743 cm-1 for C-C=O, 668 cm-1 for N-C=O, 610 cm-1 for N-
found to be ideal. Good uniformity in drug content was observed C=C. All these prominent peaks of drug are observed in formulation
and it ranged from 97.200.34 mg to 98.080.12 in all the prepared with polymer. Thus, indicating the compatibility of drug
formulation. The folding endurance was found to be between 217 with polymer. So there is no interaction take place in optimized
4.43to 233 2.36. The moisture loss in the range of 6.970.06 to formulation.
10.151.55 and moisture absorption in the range of 7.40+0.05 to
6.97+0.06 found to be satisfactory compatibility studies are carried
out between drug and polymer and were found sound and

Page | 586
[3] Jain, N. K., Controlled and Novel Drug Delivery, CBS
Publishers and Distributors, 107, 2002.

[4] Gupta JRD, Irschhiaya R, Garud N, Priyanka Tripathi, Prashant


Dubey, Patel JR, Formulation and evaluation of matrix type
transdermal patches of Glibenclamide. Int J Pharm Sci Drug
Res, 1: 46-50, (2009).

[5] Patel RP, Patel G, Baria A, Formulation and evaluation of


transdermal patch of aceclofenac. Int J Drug Deliv, 1: 41-
51(2009).

[6] Rao YM ,Gannu R, Vishnu YV and Kishan V, Development of


nitrendipine transdermal patches for in vitro and ex vivo
characterization. Curr Drug Deliv, 4: 69-76, (2007).

Fig.3.I.R spectra of Theophylline [7] Sanap GS, Dama GY, Hande AS, Karpe SP, Nalawade SV,
Kakade RS, et al., Preparation of transdermal monolithic
systems of indapamide by solvent casting method and the use
of vegetable oils as permeation enhancer. Int J Green Pharm, 2:
129-33,(2008).

[8] Murthy TEGK, Kishore VS, Effect of casting solvent on


permeability of antihypertensive drugs through ethyl cellulose
films. J Sci Ind Res, 67: 147-50, (2008).

[9] Patel HJ, Patel JS, Desai BG, Patel KD, Design and evaluation
of amlodipine besilate transdermal patches containing film
former. Int J Pharma Res Dev, 7: 1-12, (2009).

[10] Murthy TEGK and Kishore VS, Effect of casting solvent and
polymer on permeability of propranolol hydrochloride through
membrane controlled transdermal drug delivery system. Indian
J Pharm Sci, 69(5): 646-50, (2007).

Fig.4. I.R spectra of Theophylline and H.P.M.C [11] Subramanian K, Sathyapriya LS, Jayaprakash S, Prabhu RS,
Abirami A, Madhumitha B et al. An Approach to the
ACKNOWLEDGMENTS: formulation and evaluation of transdermal DDS of isoxsuprine
HCl. Int J Pharm Sci Tech, 1(1): 22-8, (2008).
The authors are thankful to M .Mohan Rao Chairman, N. Srinath
Principal of Sri Siddhartha Pharmacy College for providing the [12] Sankar V, Johnson DB, Sivanand V, Ravichandran V,
Raghuraman, S, Velrajan G et al., Design and evaluation of
facilities to carry out the research work. nifedipine transdermal patches. Indian J Pharm Sci, 65(5): 510-
REFERENCES: 515, (2003).

[13] Shinde AJ, Garala KC, More HN, Development and


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