In-Vivo Evaluation of Glipizide Floating Micropheres

Gupta Rishikesh*, Prajapati SK, Bhardwaj P and Chaurasia H.

Institute of Pharmacy, Bundelkhand University, Jhansi (UP)

*Corresponding Author E-mail: rishikeshgupt@gmail.com

 

ABSTRACT

Oral controlled drug delivery system primarily aim to increase the bioavailability of drug, but the main obstacle for oral controlled2-4 drug delivery system is inability to restrain and locate dosage form within desired region of gastrointestinal tract from where the drug has maximum absorption.Floating Microspheres of Glipizide was prepared by solvent evaporation method1. A polymeric mixture of Ethyl cellulose and hydroxy propyle methyl cellulose (HPMC). Its in-vitro5-8 performance was evaluated by the usual pharmacopoeal and other tests such as drug polymer compatibility (FTIR scan), yield (%), Micrometric properties such as Tapped density, (%). Compressibility particle size analysis (by Optical Microscopy), drug entrapment efficiency, surface topography (SEM) and in-vitro release study. The % yield of microspheres was up to 83.0±0.41. The shape and surface morphology of microspheres were studied by optical microscopy and SEM, respectively.Drug loading efficiency was found to be good. On the basis of result increasing polymer ratio increased the particle size (maximum up to 200.89±16.61). In-vivo efficiency of the optimized batch GF-1 was performed in healthy normal Wistar rats (250-300gm) by measuring the hypoglycemic effect produced after oral administration.

 

KEYWORDS: Glipizide, Floating micropheres, In-vivo study.

 


INTRODUCTION:

Floating drug delivery is of particular interest for drug that act locally in the stomach, are poorly soluble in the alkaline pH have a narrow window of absorption and are unstable in the intestinal or colonic environment. To provide good floating behavior in the stomach the density of device should be less than that of the gastric contents. Srivastava A.K. et al.6 reported cimetidine loaded floating microspheres of ethyl cellulose and HPMC. The prepared microspheres exhibited prolong drug release more than 10 hours. Glipizide 10 was used as a model drug. It is an oral hypoglycemic drug9. It is white crystalline powder. Practically it is insoluble in water and alcohol, sprangly soluble in acetone. It is soluble in dichloromethane. Its molecular weight is 444.548g/mol. Plasma half-life of glipizide is 2-5 hours. Melting point is 208-209°C. Its gastroretensive absorption is uniform, rapid and essentially complete.

 

Glipizide is sulfonylureas. Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing Depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induce the secretion of insulin.

 

Materials and Method:

The present study was involved preparation and evaluation of floating microspheres of glipizide as a model drug to enhance gastric residence time. In this study the floating microspheres will be prepared by solvent evaporation method using different ratio of ethylcellulose and hydroxypropylmethylcellulose. Glipizide was a gift sample from Micro Labs Pvt. Ltd., Kolkata. Dichloromethane, acetone, ethylcellulose, hydroxypropylmethylcellulose and tween80 were obtained from Central Drug House (CDH), Mumbai. All other chemicals were of analytical grade and were used as procured.

 

Methodology:-

Microspheres containing antidiabetic drug were prepared by solvent evaporation method. 

 

In-vivo Study:

In vivo efficiency of the optimized batch GF-1 was performed in healthy normal Wistar rats (250-300gm) by measuring the hypoglycemic effect produced after oral administration.

 

RESULT AND DISCUSSION:

Floating microspheres were prepared by solvent evaporation methods using HPMC and EC as polymer and constant solvent ratio. Various formulations of microspheres were prepared using gradually increasing EC concentration. Total eight batches of microspheres were prepared in two groups. In first group four batches were prepared with drug: EC ratio and in second group other four batches were prepared with drug: HPMC: EC ratio. (Table-1)


Table – 1: Batch specification of the prepared microspheres

Batch code

Drug:  polymer (1):  polymer (2)

Solvent ratio

Glipizide

HPMC

EC

Ethanol

DCM

Acetone

GF 1

1

0

1

1

1

1

GF 2

1

0

2

1

1

1

GF 3

1

0

3

1

1

1

GF 4

1

0

4

1

1

1

HGF 1

1

1

1

1

1

1

HGF 2

1

1

2

1

1

1

HGF 3

1

1

3

1

1

1

HGF 4

1

1

4

1

1

1

 


Fig.-1: In-vivo comparative study of glipizide and floating microspheres (Batch GF-1)

 

Table2: Reduction in blood glucose level following oral administration of glipizide suspension and floating microshpres in wistar rats.

Time (hour)

Glipizide Suspension*

Floating microspheres (Batch GF 1) Suspension*

0

63±1.69

62±2.16

1

55±0.83

56±1.42

2

42±2.16

52±1.41

3

31±1.63

47±1.63

4

39±2.94

41±0.81

5

49±0.80

32±2.16

6

52±1.63

49±2.46

7

58±0.81

52±1.68

8

62±1.65

53±1.63

 9

-

57±0.81

10

-

59±0.68

11

-

60±0.80

12

-

62±2.82

* Mean (mg/dl ) ±SD , n=3

 


The yield of microballoons was good. Microspheres showed good floating for more than 10 hours. SEM confirmed their spherical size, perforated smooth surface and a hollow cavity in them hours. In-vitro drug studies were performed in Simulated Gastric Fluid (pH 1.2). Different drug release kinetics models were applied for selected batches. It was concluded that for kinetic drug release Higuchi was the best fit model.

 

In Group-A (glipizide suspension) the rapid reduction in blood glucose was observed and maximum reduction about 50% was observed within 3 hours after oral administration. Significant hypoglycemic effect was maintained only from 0.5 to 5hours. (Table-2)

In Group-B (glipizide floating microspheres suspension) the reduction in blood glucose was sow and reaches maximum reduction of about 49% in 5 hours after oral administration. Significant hypoglycemic effect (25%) was maintained for a period of 2 to 12 hours. This significant hypoglycemic effect match with Kahn and Shechter11 results. (Table-2)

Kahn and Shechter have suggested that a 25% reduction in blood glucose levels is considered a significant hypoglycemic effect.

 

The sustained hypoglycemic effect was observed for a longer period of time in the case of glipizide floating microspheres due to the slow release and extended absorption. This sustained release formulation was more effective than the immediate release formulation of glipizide suspension in reducing fasting plasma glucose level and side effects (Fig. 1).

 

CONCLUSION:

The floating microspheres of Glipizide prepared with a suitable ratio of ethylcellulose and HPMC may provide a convenient dosage form for achieving best performabnce regarding ease of preparation, good floating ability, high encapsulation efficiency and sustained drug release over several hours. The microspheres could be dispensed by filling them into the capsules. Thus, the prepared floating microspheres may prove to be potential candidate for multiple unit delivery devices.

 

Acknowledgement:

Authors are thankful to Micro-laboratories Pvt. Ltd. Kolkata for providing generous gift of Glipizide. We are also thankful to members of animal ethical committee to providing Animals for in-vivo study.

 

REFERENCES:

1.       Kawashima Y., Niwa T., Takeuchi H., Hino T., Ito Y., Preparation of multiple unit hollow microspheres (microballoons) with acrylic resins containing tranilast and their drug release characteristics (in vivo). J Control Release. 16(1991), 279-290.

2.       Khan G. M., Controlled Release Oral Dosage Forms. Some Recent Advances in matrix type drug delivery systems. The Sciences, 1 (5) (2001), 350-354.

3.       A. J. Moes, Gasteopretentive dosage forms, Crit. Rev. Ther. Drug. Carrier Syst. 10 (1993) 143-195.

4.       A. A. Deshpande, C.T. Rhodes, N.H. Shah and A.W. Malick, Controlled release drug delivery system for prolonged gastric residence an overview. Drug Dev. Ind. Pharm. 22. (1996) 531-539. 

5.       Lee J. W., Park J .H, Robinson J.R., Bioadhesive-Based Dosage forms: The Next Generation. J. Pharm. Sci. 89(7), (2000), 850-866Ozdemir N., Ordu S., Ozkan Y., Studies of floating dosage forms of furosemide: in vitro and in vivo evaluation of bilayer tablet formulation. Drug Dev Ind Pharm. 26(2000), 857-866.

6.       Shrivatva A. K., Floating microspheres of cimetidine: Formulation, characterization and in vitro evaluation. Acta Pharm. 55(2005), 277-285.

7.       Ray S., In vitro evaluation and optimization of controlled release drug delivery system of Metformin Hydrochloride. DARU, 14(2), (2006).

8.       Ozdemir N., Ordu S., Ozkan Y., Studies of floating dosage forms of furosemide: in vitro and in vivo evaluation of bilayer tablet formulation. Drug Dev Ind Pharm. 26(2000), 857-866.

9.       Williams DA, Lemke TL, Williams L. Insulin and Oral Hypoglyecemic drugs. In  Foye’s Principles of Medicinal Chemistry, 5th Ed. New York Lippincott Williams and Wilkins: 2002. P. 641-648.

10.     Foster RH, Plosker GL, Glipizide : a review of the pharmacoeconomic implication of the extended release formulation in type 2 diabetes mellitus capsules encapsulated excipients.

11.    Kahn C.R., Shechter Y., Oral hypoglycemic agents and the pharmacology of the endocrine pancreas. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hil; 8(1991), 1461-1495.

 

 

 

 

 

Received on 06.02.2009       Modified on 02.04.2009

Accepted on 28.05.2009      © RJPT All right reserved

Research J. Pharm. and Tech.2 (3): July-Sept. 2009,;Page 474-476