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Vijay Sarkar*, Kailash Chand Yadav
Regional College of Pharmacy, Sitapura,
Jaipur, Rajasthan 302022, India

The objective of the present study was to formulate and evaluate controlled and prolonged release transdermal drug delivery system of atenolol for effective management of hypertension. The administration of atenolol via transdermal patch facilitates a direct entry of drug molecules into the systemic circulation, avoiding the first-pass metabolism and drug degradation in the harsh gastrointestinal environment, which are often associated with oral administration.To fulfill above objective transdermal patches of atenolol were prepared by solvent evaporation method using combinations of Eudragit RL100, Ethyl cellulose and PVP in different proportions. Various physicomechanical parameters like weight variation, thickness, folding endurance, drug content, water vapour transmission and tensile strength were evaluated. In-vitro Diffusion Study, skin irritation test and stability studies were also performed. In PVA and Eudragit RL 100 patches the water vapor transmission rate was found to be higher at 75% RH, RT conditions. Therefore at both % RH, RT conditions the PVA and Eudragit RL 100 patches provide the best resistance to water vapor.


PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 2

Received On: 09/01/2014; Accepted On: 21/01/2014; Published On: 10/02/2014

How to cite this article: V Sarkar, KC Yadav, Formulation and evaluation of prolonged release transdermal drug delivery system of atenolol for the treatment of hypertension, 2014, 2(2), 134-140

Transdermal drug delivery (TDDS) is defined as self contained, discrete dosage forms which, when applied to the intact skin, deliver the drug, through the skin at controlled rate to the systemic circulation. TDDS established itself as an integral part of novel drug delivery systems that breaks many barriers in drug delivery like need of assistance, intermediate dosing and uncomfortable administration1. Transdermal medication delivers a steady infusion of a drug over an ex-tended period of time. Adverse effects or therapeutic failures frequently associated with intermittent dosing can also be avoided2-4. Transdermal delivery can also increase the therapeutic value of many drugs by avoiding specific problems associated with the drugs like gastrointestinal irritation, low absorption, decomposition due to hepatic “first-pass” effect, formation of metabolites that cause side effects and short half life necessitating frequent dosing etc5. Above all this drug input can be terminated at any point of time by removing transdermal patch. However, to deliver drugs through transdermal route, it must have some desirable physicochemical properties for penetration through stratum corneum and if the drug dose required for therapeutic value is more than 10 mg/day, the transdermal delivery will be very difficult6,7. Hence relatively potent drugs are only suitable candidates for TDDS.

Atenolol is a β1-receptor selective antagonist and is mainly used in treating hypertension, angina, heart failure, and myocardial infarction; chemically, it is 4-(2-hydroxyl-3-isopropyl aminopropoxy) phenylacetamide. The physicochemical properties of atenolol, i.e., slight water solubility, low molecular weight (266.336), and its suitable elimination half-life (6–7 h), make it a suitable candidate for administration by TDDS8,9.

The polymeric film containing Eudragit RL 100, Ethyl cellulose, PVP anddrug (Table. 1.) were selected for transdermal administration based on evaluation studies10,11. The polymeric films were prepared by mercury substrate method employing PEG-400 as plasticizer. Two different penetration enhancers Urea and Dimethyl sulphoxide (DMSO) were employed in the study. The dried polymeric film was evaluated using different parameters including thickness uniformity, drug content of the film, in vitro drug release from films and in vitro skin permeation of drug12.


2.1 Materials
Atenolol was obtained as a gift sample from Fourt’s India, Chennai. Eudragit RL100 and Eudragit RS (S. D. Fine Chem. Ltd., Mumbai), Ethyl cellulose, PVP K-30 (S. D. Fine Chem. Ltd., Mumbai), Urea and Dimethyl sulphoxide (DMSO) (S. D. Fine Chem. Ltd., Mumbai) were procured for above study. All other chemicals used were of analytical grade.

2.2 Preparation of Atenolol-Containing Transdermal Patches
The transdermal patch was prepared by solvent evaporation technique on mercury substrate. Polymer solution was prepared in ethanol (10 ml) and to it atenolol was added. The plasticizer and permeation enhancer were added during patch casting. The solution was poured on glass rings placed on mercury surface and allowed to dry in air for 24 h. Circular patches of 2 cm diameter (3.14 cm2) were cut from semi dried patches and placed in vacuum desiccators7.

2.3 Evaluation of patch

2.3.1. Measurement of thickness and weight variation
Thickness was measured using micrometer screw gauge (Mitutoyo, Japan). Each patch was measured for thickness at sixdifferent points to ascertain thickness uniformity in patch13,14. Weight variation was determined by weighing three patches individually, from each batch and the average weight was calculated5(Table 2).

2.3.2. Tensile strength
Mechanical properties of the polymeric patches were conveniently determined by measuring their tensile strength15. The tensile strength of the patches was determined by using a tensile strength instrument as described by Agarwal GP, et al (Fig. 1.). Average reading of three patches was taken as the tensile strength. The transdermal patch was fixed to the assembly, the weights required to break the patch was noted, and simultaneously elongation was measured with the help of a pointer mounted on the assembly and calculated the tensile strength of the patch using the following formula

T. S.  = break force/ a.b (1+ΔL/L)

Where   a,   b   and   L   are   width,   thickness   and   length   of   the   patch respectively.
ΔL is the elongation of patch at break point.
Break force = Weight required to break the patch (Kg)16.

2.3.3.Folding Endurance
The folding endurance was measured manually for the prepared patches. It is expressed as number of times the patch is folded at the same place either to break the patch or to develop visible cracks. This is important to check the ability of sample to withstand folding.  This also gives an indication of brittleness17. This was determined by repeatedly folding one patch at the same place till it break (Table 2). The number of times the patch could be folded at the same place without breaking/cracking gave the value of folding endurance18.

2.3.4. Water vapour transmission
The water vapour transmission is defined as the quantity of moisture transmitted through unit area of a patch in unit time. The water vapour transmission data through transdermal patches are important in knowing the permeation characteristics19. Glass vials of equal diameter were used as transmission cells. These transmission cells were washed thoroughly and dried to constant weight in an oven. About 1 gm of fused calcium chloride as a desiccant was taken in the vials and the polymeric patches were fixed over the brim with the help of an adhesive tape. These pre-weighed vials were stored in a humidity chamber at RH of 80% with the temperature set to 30ºC for a period of 24 hours (Table 2). The weight gain was determined every hour up to a period of 24 hours20.

The water vapour transmission was calculated using the equation

Rate = WL/S

Where W is gm of water permeated / 24 hr. L is thickness of the patch S is exposed surface area of the patch21.

2.3.5.Drug Content Uniformity
In order to ascertain the uniform distribution of the drug in the patches, the content uniformity test was carried out utilizing the pharmaceutical standard by means of a UV/Visible spectrophotometer. The transdermal patch  of  specified  area  (3.14  cm²)  was  dissolved  in  100  ml  pH  7.4 phosphate buffer. This was then shaken in a mechanical shaker for 2 h to get a homogeneous solution and filtered (Table 2). A blank was performed using a drug free patch treated similarly. The drug content in each formulation was determined by measuring the absorbance at 274 nm after suitable dilution using a UV/visible spectrophotometer22.



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