MICROBALLOONS DELIVERY SYSTEM: AN INNOVATIVE ACCEPTABLE APPROACH IN GASTRORETENTIVE DRUG DELIVERY

About Authors:
Yashodhara Choubey*, Mr. Govind Bhandari, Mr. Avnish Sharma, Mr. Mukesh Mehra
Mahakal Institute of Pharmaceutical Studies,
Ujjain (M.P.), India
*yashodhara.juhipharma@gmail.com

Abstract
Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The Microballoons delivery systems are useful in such application. Microballoons are gastro-retentive drug delivery systems based on non-effervescent approach. Microballoons are in strict sense, spherical empty particles without core and ideally having a size less than 200 micrometer. Microballoons are low-density systems that have sufficient buoyancy to float over gastric contents and remain in stomach for prolonged period. The drug is released slowly at desired rate resulting in increased gastric retention with reduced fluctuations in plasma drug concentration. Microballoons improve patient compliance by decreasing dosing frequency; better therapeutic effect of short half-life drugs can be achieved. These are primarily controlled release drug delivery systems, which gets retained in the stomach for longer periods of time, thus helping in absorption of drug for the intended duration of time. Gastric retentive drug delivery devices can be useful for the spatial and temporal delivery of many drugs because of buoyancy.

REFERENCE ID: PHARMATUTOR-ART-1892

INTRODUCTION
Oral administration is the most convenient and preferred means of any drug delivery to the systematic circulation. Oral controlled release drug delivery have recently been of increasing interest in pharmaceutical field to achieve improved therapeutic advantages, such as ease of dosing administration, patient compliance and flexibility in formulation. Drugs that are easily absorbed from gastrointestinal tract (GIT) and have short half-lives are eliminated quickly from the systemic circulation. Frequent dosing of these drugs is required to achieve suitable therapeutic activity. To avoid this limitation, the development of oral sustained-controlled release formulations is an attempt to release the drug slowly into the gastrointestinal tract (GIT) and maintain an effective drug concentration in the systemic circulation for a long time. Microballoons is an approach to prolong the gastric retaintion which have a bulk density lower than gastric fluids and thus remain buoyant in stomach for a prolonged period of time, without affecting the gastric emptying rate. This results in an increase in gastric retention time and a better control of fluctuations in plasma drug concentrations. These microballoons are characteristically free flowing powders consisting of proteins or synthetic polymers, ideally having a size less than 200 micrometer.

ADVANTAGES OF MICROBALLOONS
1. Improves patient compliance by decreasing dosing frequency.
2. Bioavailability enhances despite first pass effect because fluctuations in plasma drug concentration is avoided, a desirable plasma drug concentration is maintained by continuous drug release.
3. Gastric retention time is increased because of buoyancy.
4. Enhanced absorption of drugs which solubilise only in stomach
5. Drug releases in controlled manner for prolonged period.
6. Site-specific drug delivery to stomach can be achieved.
7. Superior to single unit floating dosage forms as such microspheres releases drug uniformly and there is no risk of dose dumping.
8. Avoidance of gastric irritation, because of sustained release effect.
9. Better therapeutic effect of short half-life drugs can be achieved.

MECHANISM OF FLOATING MICROBALLOONS
When microballoonscome in contact with gastric fluid the gel formers, polysaccharides, and polymers hydrate to form a colloidal gel barrier that controls the rate of fluid penetration into the device and consequent drug release. As the exterior surface of the dosage form dissolves, the gel layer is maintained by the hydration of the adjacent hydrocolloid layer. The air trapped by the swollen polymer lowers the density and confers buoyancy to the microspheres. However a minimal gastric content needed to allow proper achievement of buoyancy.

METHODS OF PREPARATION OF MICROBALLOONS
Microballoonsare prepared by solvent diffusion and evaporation methods to create the hollow inner core. Polymer is dissolved in an organic solvent and the drug is either dissolved or dispersed in the polymer solution. The solution containing the drug is then emulsified into an aqueous phase containing polyvinyl alcohol to form oil in water emulsion. After the formation of a stable emulsion, the organic solvent is evaporated either by increasing the temperature under pressure or by continuous stirring. The solvent removal leads to polymer precipitation at the o/w interface of droplets, forming cavity and thus making them hollow to impart the floating properties.

CHARACTERIZATION OF MICROBALLOONS
Micromeritic properties

particle size,
tapped density,
compressibility index,
true density and flow properties

Floating Behavior

In-VitroRelease Studies

In-VivoStudies

CONCLUSION
Drug absorption in the gastrointestinal tract is a highly variable phenomenon and prolonging gastric retention of the dosage form extends the time for drug absorption and attempts to make it more uniform as well as reproducible. Microballoons Drug Delivery promises to be a potential approach for gastric retention.The microballoons become an additional advantage for drugs that are absorbed primarily in the upper part of GI tract, i.e., the stomach, duodenum, and jejunum. Some of the unresolved, critical issues like the quantitative efficiency of floating delivery systems in the fasted and fed states, role of buoyancy in enhancing GRT of FDDS and more than that formulation of an ideal dosage form to be given locally to eradicate H.Pylori, responsible for gastric ulcers world wide.

References

Atyabi, F., Sharma, H.L., Mohammad, H., Fell, J. T., In-vivo evaluation of a novel gastroretentive formulation based on ion exchange resins, J. Control. Rel. 1996; 42: 105-13.
Baumgastner, S., Kristel, J., Vreer, F., Vodopivec, P., Zorko, B., Optimisation of floating matrix tablets and evaluation of their gastric residence time, Int J Pharm 2000; 195:125 35.
Davis, S. S., Formulation strategies for absorption windows, Drug Dev Tech 2005; 10(4):249-58.
Derivative for the treatment of gastritis. Int.J.Pharm. 2008,356,88-94
Deshpande, A. A., Shah, N.H., Rhodes, C.T., Malick, W., Development of a novel controlled release system for gastric retention, Pharm. Res. 1997; 14 (6): 815-9.
Floating microspheres, Int.J.Pharm. 2008, 358,82-90
Goole J, Vanderbist F, Aruighi K. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms. Int J Pharm 2007; 334: 35-41.
Iannucelli V, Coppi G, Bernabei MT, Camerorni R. Air compertment multiple- unit system for prolonged gastric residence. Part-I Formulation study. Int J Pharm 1998; 174: 47-54.
Jain N K. Controlled Novel Drug Delivery. Ist Eds CBS Publishers and Distributors, New Delhi.2002 pp.236-55.
Janga S., Lee J., Park S. Gastroretentive drug delivery system of DA-6034, a new flavonoid
Nasa,Praveen, Mahant, Sheefali,Sharma Deepika,”Floating system: A Novel approach towards gastroretentive drug delivery system”,International journal of pharmacy and pharmaceutical science, vol-2,issue-3,p.no-2-7
Ninan M., Lu X., Wanga Q., Zhanga X. Development and evaluation of new sustainedrelease
Rajesh Patel; Microbubble: An ultrasound contrast agent in molecular imaging, Pharma Times, May 2008;Vol. 40 ; Pg 15.
Sharma S, Pawar A. Low density multiparticulate system for pulsatile release of meloxicam. Int J Pharm 2006; 313:150-58.
Shirwalkar, A. A., Kumar, S. M., Jacob, S., Recent developments in floating drug delivery systems for gastric retention of drugs, An overview. Indian drugs. 2006:43(9); 697-704.