An Updated Review on Microballoon for Better Approach in Gastro Retention

 

Audumbar Digambar Mali*, Ritesh Suresh Bathe

Department of Pharmaceutics, Sahyadri College of Pharmacy, Methwade,

Sangola-413307, Solapur, Maharashtra, India.

*Corresponding Author E-mail: maliaudu442@gmail.com

 

ABSTRACT:

The purpose of this review on microballoons is to accumulate the recent literature with special focus on the recent development on floatation to achieve gastric retention. Microballoons are emerging as the most promising drug delivery as it overcome many limitations of conventional drug delivery system. As microballoons delivery system provides longer retention in gastric pH, hence longer is the residence time and therefore enhance the solubility of drugs that are less soluble in high pH environment. The formation of cavity inside the microsphere depends upon the preparation temperature and the surface smoothness determines the floatability and the drug release rate of the microballoons.

 

KEYWORDS: Microballoons, Gastroretentive, Bioavailability, Sustained Effect, Oral Administration.

 

 


INTRODUCTION:

One of the most interesting fields of research in pharmaceutics is the development of new delivery systems for the controlled release of drugs [1]. Gastroretentive drug delivery is an approach to prolong gastric residence time, thereby targeting site-specific drug release in the upper gastrointestinal tract (GIT) for local or systemic effects. Gastroretentive dosage forms can remain in the gastric region for long periods and hence significantly prolong the gastric retention time (GRT) of drugs. 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. [1, 2]

 

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. Prolonged gastric retention improves bioavailability, increases the duration of drug release, reduces drug waste and improves the drug availability that is less soluble in a high pH environment. [3, 4]

 

Classification: - Floating systems can be classified into two systems:

1) Effervescent systems

Volatile liquid containing systems

Gas-generating Systems

2) Non-Effervescent Systems

Colloidal gel barrier systems

Microporous Compartment System

Alginate beads

Microballoons

 

Microballoons: -

Floating microballoons are gastro-retentive drug delivery systems based on non-effervescent approach. Microballoons are in strict sense, spherical empty particles without core. These microballoons are characteristically free flowing powders consisting of proteins or synthetic polymers, ideally having a size less than 200μm. Solid biodegradable microballoons incorporating a drug dispersed or dissolved throughout particle matrix have the potential for controlled release of drugs. Gastro-retentive floating microballoons are low density systems that have sufficient buoyancy to float over gastric contents and remain in stomach for prolonged period. As the system floats over gastric contents, the drug is released slowly at desired rate resulting in increased gastric retention with reduced fluctuations in plasma drug concentration. Microballoons loaded with drugs in their other polymer shelf were prepared by simple solvent evaporation or solvent diffusion / evaporation methods to prolong the gastric retention time (GRT) of the dosage form with continuously floating over the surface of an acidic dissolution media containing surfactant for >12 h. [5, 6]

 

Fig. : Microballoons

 

Advantages: -

a. Reduces the dosing frequency and thereby improve the patient compliance.

 

b. Better drug utilization will improve the bioavailability and reduce the incidence or intensity of adverse effects and despite first pass effect because fluctuations in plasma drug concentration is avoided, a desirable plasma drug concentration is maintained by continuous drug release.

c. Hollow microballoons are used to decrease material density and Gastric retention time is increased because of buoyancy.

 

d. Enhanced absorption of drugs which solubilise only in stomach

e. Drug releases in controlled manner for prolonged period.

 

f. Site-specific drug delivery to stomach can be achieved.

g. Superior to single unit floating dosage forms as such microballoons releases drug uniformly and there is no risk of dose dumping.

 

h. Avoidance of gastric irritation, because of sustained release effect.

 

i. Better therapeutic effect of short half-life drugs can be achieved. [7, 8]

 

Limitations:

Some of the disadvantages were found to be as follows

a. The modified release from the formulations.

 

b. The release rate of the controlled release dosage form may vary from a variety of factors like food and the rate of transit though gut.

 

c. Differences in the release rate from one dose to another.

 

d. Controlled release formulations generally contain a higher drug load and thus any loss of integrity of the release characteristics of the dosage form may lead to potential toxicity.

 

e. Dosage forms of this kind should not be crushed or chewed. [9]

 

Methods of Preparation: -

a. Solvent Evaporation Method: Floating multiparticulate dosage form can be prepared by solvent diffusion and evaporation methods to create the hollow inner core. The 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 suitable additive (surfactants / polymer) 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 oil/water interface of droplets, forming cavity and thus making them hollow to impart the floating properties. The polymers studied for the development of such systems include cellulose acetate, chitosan, Eudragit, Acrycoat, Methocil, polyacrylates, polyvinyl acetate, carbopol, agar, polyethylene oxide and polycarbonate.

 

 


 

Fig. 2: Formulation of floating microballoon

 


b. Emulsion Solvent Diffusion Method: In the emulsion solvent diffusion method the affinity between the drug and organic solvent is stronger than that of organic solvent and aqueous solvent. The drug is dissolved in the organic solvent and the solution is dispersed in the aqueous solvent producing the emulsion droplets even though the organic solvent is miscible. (The organic solvent diffuse gradually out of the emulsion droplets in to the surrounding aqueous phase and the aqueous phase diffuse in to the droplets by which drug crystallizes. [10]

 

Characterization of the Optimized Microballoons: -

1. Determination of bulk density, tapped density and particle density: - Different fractions of the optimized formulation (1g) were taken into a 10ml graduated measuring cylinder separately and the volume was noted down. The graduated measuring cylinder was tapped 50 times using USP bulk density apparatus .The bulk density and tapped densities were determined using the following formula:

 

 

 

Particle density of different fractions was determined by the liquid displacement method by suspending the microballoons in a solvent in which the microballoons were insoluble like distilled water. [11]

 

2. Particle size analysis: - Particle size analysis was carried out using the optical microscopic method with the help of a calibrated eye piece micrometer. The size of around 100 particles was measured and median diameter was calculated. [12]

3. Scanning Electron Microscopy (SEM): - SEM was performed for morphological characterization of microballoons using scanning electron microscope. They were mounted directly onto the SEM sample stub using double-sided sticking tape and coated with gold film (thickness, 200nm) under reduced pressure (0.001mmHg). [13]

 

4. In vitro drug release study: - A USP (United State Pharmacopoeia) basket apparatus has been used to study in vitro drug release from microballoons. In this, drug release was studied using a USP dissolution apparatus type I at 100 rpm in distilled water and 0.1 mol HCl (pH 1.2) as dissolution fluid (900 ml) maintained at 370.5C. Withdrawn samples were analyzed spectrophotometrically. The volume was eplenished with the same amount of fresh dissolution fluid each time to maintain the sink condition. [14]

 

5. Buoyancy percentage: - Appropriate amount of microballoons were placed in 900 ml of 0.1 N hydrochloric acid. The mixture was stirred at 100 rpm in a dissolution apparatus for 8 hrs. After 8 hrs, the layer of buoyant microballoons were pipetted and separated by filtration. Particles in the sinking particulate layer were separated by filtration. Particles of both types were dried in a dessicator until constant weight. Both the fractions of microballoons were weighed and buoyancy was determined by the weight ratio of floating particles to the sum of floating and sinking particles.

 

% Buoyancy = [Wf / Wf + Ws)] x 100;

 

Where Wf and Ws are the weights of the floating and settled microspheres. [15]

 

6. Stability Studies: - During the storage if one performs studies at normal temp it will take a longer time and hence it would be convenient to carry out the accelerated stability studies where the product is stored under extreme conditions of temperature. Optimized formulation sealed in aluminum packaging coated inside with polyethylene, and various samples were kept in the humidity chamber maintained at 40C and 75% RH for 2 months. At the end of studies, samples were analyzed for the physical appearance, drug content and drug release. [16]

 

7. Release kinetics: - Data obtained from in-vitro release studies were fitted to various kinetic equations to find out the mechanism of drug release from the ethyl cellulose microsphere. The kinetic models used were:

 

Qt = K0 t (zero-order equation)

ln Qt = ln Q0 - K1 t (first-order equation)

Qt = Kh t1/2 (Higuchi equation)

 

Where Qt is the amount of drug release in time t, Q0 is the initial amount of drug in the microsphere, and K0, K1, and Kh are rate constants of zero order, first order and Higuchi equations, respectively. Further to confirm the mechanism of drug release, the first 60% of drug release was fitted in Korsemeyer- Peppas model (power law).

 

Mt / M= k tn

 

where Mt is the amount of drug release at time t and Mis the amount release at time t = , thus Mt / Mis the fraction of drug released at time t, k is the kinetic constant, and n is the diffusion exponent which can be used to characterize both mechanism for both solvent penetration and drug release. [17]

 

Applications: -

1.       Solid and hollow microballoons vary widely in density and, therefore, are used for different applications. Hollow microballoons are typically used as additives to lower the density of a material. Solid microballoons have numerous applications depending on what material they are constructed of and what size they are.

 

2.       Hollow microballoons can greatly improve the pharmacotherapy of the stomach through local drug release, leading to high drug concentrations at the gastric mucosa, thus eradicating helicobacter pylori from the submucosal tissue of the stomach and making it possible to treat stomach and duodenal ulcers, gastritis and oesophagitis.

 

3.       These microballoons systems provide sustained drug release behavior and release the drug over a prolonged period of time.

 

4.       The drugs recently reported to be entrapped in hollow microballoons include Prednisolone, Lansoprazole, Celecoxib, Piroxicam, Theophylline, Diltiazem hydrochloride, Verapamil hydrochloride and Riboflavin, Aspirin, Griseofulvin, Ibuprofen, Terfenadine.

 

5.       Floating microballoons can greatly improve the pharmacotherapy of stomach through local drug release. Thus, eradicating Helicobacter pylori from sub-mucosal tissue of the stomach are useful in the treatment of peptic ulcers, chronic gastritis, gastro esophageal reflux diseases etc. Hollow microballoons of ranitidine HCl are also developed for the treatment of gastric ulcer.

 

6.       Floating microballoons are especially effective in delivery of sparingly soluble and insoluble drugs. It is known that as the solubility of a drug decreases, the time available for drug dissolution becomes less adequate and thus the transit time becomes a significant factor affecting drug absorption. For weakly basic drugs that are poorly soluble at an alkaline pH, hollow microballoons may avoid chance for solubility to become the rate-limiting step in release by restricting such drugs to the stomach. The gastro-retentive floating microballoons will alter beneficially the absorption profile of the active agent, thus enhancing its bioavailability.

 

7.       The floating microballoons can be used as carriers for drugs with so-called absorption windows, these substances, for example antiviral, antifungal and antibiotic agents (Sulphonamides, Quinolones, Penicillins, Cephalosporins, Aminoglycosides and Tetracyclines) are taken up only from very specific sites of the GI mucosa.

 

8.       Hollow microballoons of non-steroidal anti inflammatory drugs are very effective for controlled release as well as it reduces the major side effect of gastric irritation; for example floating microballoons of Indomethacin are quiet beneficial for rheumatic patients. [18, 19]

 

CONCLUSION:

In recent review we concluded that the floating hollow microcapsules showed gastroretentive controlled release delivery system, promises to be a potential approach for gastric retention. Although there are number of difficulties to be worked out to achieve prolonged gastric retention, a large number of companies are focusing toward commercializing this technique. Hollow microballoons are low-density, sufficient buoyancy to float over gastric contents and remain in stomach for prolonged period. As the system floats over gastric contents, the drug is released slowly at desired rate resulting in increased gastric retention with reduced fluctuations in plasma drug concentration. Floating hollow microcapsules of melatonin showed gastroretentive controlled release delivery system.

 

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Received on 03.07.2015 Accepted on 02.08.2015

Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 5(3): July-Sept.; Page 188-192

DOI: 10.5958/2231-5659.2015.00028.4