final .cdr

From the technological point of view, an ideal buccal dosage
form must have three properties; It must maintains its
position in the mouth for a few hours, release the drug in
controlled fashion and provide drug release in a
unidirectional way towards mucosa.
Atenolol (beta blocker), has been widely used in the
management of hypertension. The drug is well absorbed
from the gastrointestinal tract but its bioavailability is low
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(54%) due to extensive first pass metabolism. Since the
buccal route bypasses first-pass effect, the dose of atenolol
could be reduced by 50%. The physicochemical properties
of atenolol, its suitable half-life (6-7 h) and low molecular
weight (266.34) makes it a suitable candidate for
administration by buccal route. The effective permeation of
the drug through bovine buccal mucosa has already been
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reported.
In the present study, an attempt was made to design
efficacious and prolonged release mucoadhesive tablets of
atenolol using various polymers to avoid first pass
metabolism, to reduce dosing frequency and to improve
patient compliance with improved bioavailability.
MATERIALS AND METHODS
Atenolol was gifted by Rajat Pharmachem Ltd,
Ankaleshwar, Gujarat. Ethyl cellulose was gifted by (Arihant
Trading co., Mumbai, India), hydroxypropyl
methylcellulose 15 cps, 50 cps, (Colorcon Asia Pvt. Limited,
Verna, India) and carbopol 934p were gifted by ( ShinEtsu
Chemical Co. Ltd Japan). All other materials were of
analytical or pharmacopoeial grade and used as received.
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Preparation of the buccal tablets
Preparation: Direct compression method has been
employed to prepare buccal tablets of atenolol using HPMC
15cps, HPMC 50cps and Carbopol 934p as polymers.
S B Shirsand et al Design and Evaluation of Atenolol Bilayer Buccal Tablets
Procedure: All the ingredients including drug, polymer
and excipients were weighed accurately according to the
batch formula (Table 1). The drug is thoroughly mixed with
mannitol on a butter paper with the help of a stainless steel
spatula. Then all the ingredients except lubricant were
mixed in the order of ascending weights and blended for 10
min in an inflated polyethylene pouch. After uniform mixing
of ingredients, lubricant was added and again mixed for 2
min. The prepared blend (100 mg) of each formulation was
pre-compressed, on a 10-station roatory tablet punching
machine (Clit, Ahmedabad) at a pressure of 0.5 ton and
turret speed of 2 rpm to form single layered flat-faced tablet
of 9 mm diameter. Then, 50 mg of ethyl cellulose powder
was added and final compression was done at a pressure of
3.5 tons and turret speed of 2 rpm to get bilayer tablet.
Evaluation of buccal tablets
Table 1: Composition of Buccoadhesive Tablets
*
Ingredients Formulation code
The prepared batches of tablets were evaluated for weight
variation, hardness, friability, drug content uniformity,
swelling index, surface pH, ex vivo mucoadhesive strength, invitro
drug release, short-term stability (IR spectroscopy) and
drug-excipient interaction.
Twenty tablets were selected at random and weighed
individually. The individual weights were compared with the
average weight for determination of weight variation.
Hardness and friability of the tablets were determined by
using Monsanto hardness tester and Roche friabilator
respectively. For content uniformity test, ten tablets were
weighed and powdered. The powder equivalent to 25 mg of
drug was extracted into methanol, filtered through 0.45 μm
membrane filter disc (Millipore Corporation) and was
analyzed for atenolol after appropriate dilution by
measuring the absorbance at 226.6 nm, against blank. The
drug content was calculated using the standard calibration
curve. The mean percent drug content was determined as an
average of three determinations.
(mg/tablet) AT AT At AT AT BT BT BT BT BT
0 1
2 3 4 0 1 2 3 4
Atenolol 25 25 25 25 25 25 25 25 25 25
Carbopol 934P --- 2 4 8 12 --- 2 4 8 12
HPMC 50 cps 50 48 46 42 38 --- --- --- — —
HPMC 15 cps --- --- --- --- --- 50 48 46 42 38
Mannitol 14 14 14 14 14 14 14 14 14 14
PVP K-30 6 6 6 6 6 6 6 6 6 6
Aspartame 3 3 3 3 3 3 3 3 3 3
Mg. stearate 2 2 2 2 2 2 2 2 2 2
Ethyl cellulose 50 50 50 50 50 50 50 50 50 50
Total weight 150 150 150 150 150 150 150 150 150 150
*Weights expressed as mg per tablet; HPMC- hydroxypropyl methylcellulose; PVP- polyvinyl pyrolidone;
AT-formulation containing HPMC 50 cps; BT-formulation containing HPMC 15 cps.
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RJPS, Apr-Jun, 2011/ Vol 1/ Issue 1