10-05-2014, 12:27 PM
Formulation development and evaluation of glyburide beads for controlled release
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ABSTRACT
Oral controlled drug delivery systems represent the most popular form of controlled drug delivery systems for the
advantages of oral route of drug administration. In certain conditions conventional drug release pattern is not
suitable like Diabetes mellitus, Asthma, cardiovascular diseases Arthritis, Peptic ulcer etc. this present study an
attempt was made to formulate controlled release beads of Glyburide by using Sodium alginate, HPMC K100M,
Carbopol 940 and Calcium Chloride(fused).Beads were successfully prepared by Ionotropic Gelation Method .The
prepared beads evaluated for various parameters lke encapsulation efficacy, swelling index, Mean particle size,
flow properties and in vitro release. The yields were varies from 88-93.8% and encapsulation efficacy is up to
91.2% which encourage the investigation. The in-vitro dissolution profile of optimized formulation batch i.e., F4 is
resulted up 12 hours. The various parameters of model equation of beads containing Glyburide in vitro kinetic
release were thoroughly investigated and it was seen that the statistically significant confined to Zero- order,
Higuchi and Korsmeyer- Peppas model. To establish the release kinetic, Korsmeyer- Peppas model shows the
prominent release characteristics.
INTRODUCTON
Oral drug delivery is the most used and preferred route of administration with the obvious advantage of ease of
administration and patient acceptance. To develop a drug delivery system for oral administration, it is necessary to
optimize not only the release rate of an active ingredient from the system but also the residence time of the system in
the gastrointestinal tract[1]. our population afflicted with diabetes specially the Type-2, which are not dependent on
insulin production.The efficiency of any drug therapy can be described by achieving desired concentration of the
drug in blood or tissue, which is therapeutically effective and non toxic for a prolonged period. This goal can be
achieved on the basis of proper design of the dosage regimen. Microspheres have potential to deliver drug in a
controlled fashion. [2] Glyburide is a second-generation sulfonyl urea that is an orally bioavailable hypoglycemic
agent used in the management of type 2 diabetes. Different research has reported that glyburide has a low
bioavailability, which is attributed to its poor dissolution properties. It has short half life of 4-6 hours. Glyburide in
oral conventional dosage form has the dosage regime of three times a day due to having short elimination half life of
5 hour. Controlled release concept and technology has received increasing attention in the face of growing
awareness to toxicity and ineffectiveness of drugs. When drugs are administered as conventional dosage forms such
as tablets, capsules etc. usually produce wide ranging fluctuations in drug concentration in the blood stream and
tissues and consequently undesirable toxicity and efficiency[3].
Drug entrapment efficiency
Microspheres equivalent to 10 mg of Glyburide were crushed in a glass mortar and pestle and the powdered beads
were suspended in 100 ml of phosphate buffer pH 7.4. The resulting mixture was kept shaking on mechanical shaker
for 24 h. After 24 hours, the solution was filtered, 1ml of the filtrate was pipette out and diluted to 10 ml using of
phosphate buffer pH 7.4 and analyzed for the drug content using UV Visible spectrophotometer at 230 nm.
In vitro release studies
In vitro dissolution studies for all the prepared dried beads after weighing were carried out in 900 ml of alkaline
phosphate buffer of pH 7.4 using USP XXIV type-I (Basket) dissolution rate test apparatus (Model L6, M/S
Electrolab). A speed of 50 rpm and a temperature of 37±1°C were used in each test. A 5 ml aliquot was withdrawn
at different time intervals , filtered and replaced with 5 ml of fresh dissolution medium. The volume of each sample
was replaced with the same volume of phosphate buffer (pH 7.4) to maintain the sink conditions. The amount of
glyburide released from the beads was analyzed using a UV spectrophotometer at 230 nm. All the dissolution
experiments were conducted in triplicate and the mean values are reported. The results are given in Table 8 .
CONCLUSION
The Glyburide beads were prepared by ionotropic gelation method using
u
sodium alginate,
lginate, carbopol 940, HPMC K
100 M as polymers. As Glyburide has short half life of 4-6
6 hrs, this can be increased by using combination of
polymers for a sustained release of drug. This method is performed by using CaCl2 solution as cross linking agent
for hardening of alginate beads.After preparation the obtained beads
beads were evaluated for % yield, drug entrapment
efficiency, swelling index, in vitro drug release studies and results were tabulated. The obtained microspheres were
found to be free flowing, discrete and the %yield was found to be 88 to 93.8%,
.8%, drug entrapment
entrap
efficiency was
found to be 82.7 to 91.2 %,and swelling index of beads were satisfactory. The dissolution was performed for 12 hrs
and the drug release was found to be 99.42% for formulation with combination of polymers (F4) and found to be
significant optimized batch, which may be the ideal batch .Therefore usage of combination of polymers gave
significant results and satisfactory when compared to single use of polymers