Microballoons: An Advanced Avenue for Gastro Retentive Drug Delivery System

 

Pratibha. B. Wakchaure1, Maya. Y. Gaikwad2*

1Student, SMBT Institute of D. Pharmacy, Dhamangaon, Nashik.

2Lecturer, SMBT Institute of D. Pharmacy, Dhamangaon, Nashik.

*Corresponding Author E-mail: gaikwadmau012@gmail.com

 

ABSTRACT:

The motivation of writing this review on micro balloons is a Gastro retentive drug delivery system are micro balloons (hollow microsphere) are a drug delivery system that promises to be a potential approach for gastric retention. Microballoons drug delivery system is novel drug delivery on the foundation of non- effervescent system that containing empty particles of spherical shape without core ideally having a size less than 200 micrometers which is designed to be retained in the stomach for a prolonged period of time and release their active ingredients and thereby enable sustained and prolonged input of the drug in the upper part of the gastrointestinal (GI) tract. They are gastro retentive drug-delivery systems, which provide controlled release properties for a drug. Recently gastro retentive drug delivery system (GRDDS) are gaining wide acceptance for drugs with narrow absorption windows, decreased stability at high alkaline pH, and increased solubility at low pH. The design of this article is to compose the various gastro retentive arrive. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling retention i.e. high density, floating, bio-or that adheres to a mucous membrane (adjective), extensile, attractor etc. In addition of central element controlling gastro retention, superiority and finally future potential are discussed.

 

KEYWORDS: Microballoons, Gastro retentive drug delivery system, Holloshperes, Polymers, Cross linking agents.

 

 


INTRODUCTION:

Gastro retentive drug delivery system (GRDDS) can overcome drawbacks associated with oral drug delivery, by defeating natural physiological principles - The oral delivery of drugs with a narrow absorption window in the gastrointestinal tract (GIT) is often restricted by poor bioavailability with conventional.

 

Dosage forms due to incomplete the recent era various technologies have been made in research and development of controlled various physiological difficulties extended release tablet to increase the development of a gastro retentive drug delivery system in this work, the details of formulation of tablets. Tabletting and in the development of controlled- release gastro retentive drug delivery system. Elimination of side effect reducing the fluctuation of drug concentration and frequency of dosing; it optimized thereby and better patient compliance.

 

Gastro retentive drug delivery system (GRDDS):

Gastro retentive 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 effects11.

 

Floating drug delivery system:

The floating drug delivery system (FDDS) is also called hydrodyanamically balanced system (HBS). in FDDS, the carries float in gastric juice to ensure that drugs do not leaves stomach shortly. The drug is slowly at the constant rate from the system. Floating drug delivery systems (FDDS) are those systems which have a bulk density less than gastric fluids and because of this, these article system remains buoyant (3-4hours) for a prolonged periods of time in the stomach without affecting the gastric emptying rate.

 

It can be classified into two systems.

      Effervescent system:

Effervescent floating drug delivery system means release of carbon dioxide gas due to reaction of acids and bicarbonates. e.g. of acids are citric acid, tartaric acid and e.g. of bicarbonate/carbonate are sodium bicarbonate, calcium carbonate.

 

      Non-Effervescent System:

The study included the non effervescent system formulation of floating tablets using polymers like chitosan and karaya gum as matrix forming agents.

Micro porous compartment system

Hydro colloidal gel barrier system

Hollow microsphere (micro balloons)2.

 

      Microballoons:

Microballoons (Hollow microsphere) are a drug delivery system that promises to be a prospective approach for gastric retention - micro balloons drug delivery system are based on a non -effervescent system containing empty particles of spherical shape without core identically having a size less than 200 micrometers1.

 

The floating micro balloons showed gastro retentive controlled release delivery with competent means of enhancing the bioavailability and promises to be a, Microballoons are considered as one of the most like approving floating systems with the unique advantage of multiple units system as well as better floating properties, because of central hollow space within the microsphere. Hollow or unfilled microspheres (micro balloons) of acrylic resins, eudragit, hydromellose, polyethylene oxide, cellulose acetate, polystyrene floatable shells, polycarbonate floating balloons and glucire floating granules are the current advancements9.

 

      Mechanism of Microballoons:

When micro balloons come in contact with gastric fluid, the drug is released slowly at desired rate ensuing in increased gastric retention with condensed fluctuation in plasma drug concentration. However a minimal gastric content needed to allow proper attainment of buoyancy.

 

Materials for Preparation of Microballoons:

1.    Drugs:

Drug is defined as, a medicine or other substances which has a physiological effect when ingested or otherwise introduced into the body. Drug with narrow therapeutic index in GI tract, mainly absorbed from stomach and retain upper part of GIT. Locally act in the stomach, degrade or corrupt in the colon and disturb normal colonic bacteria. e.g. Aspirin, salicylic acid, para amino benzoic acid, furosemide, calcium, supplements, Riboflavin, levodopa, Antacids, microprostol, Rantidine Hcl.

 

2.    Polymers:

Polymers like Cellulose acetate, chitosan, eudragit, arycoat, methocil, polyacrylates, polyvinyl acetate, carpool, agar, polyethylene oxide, polycarbonates, acrylic resins and polythene.

 

3.    Solvents:

Microspheres can be defined as spherical solid particles with an inside and internal matrix structure. Method by which to determine the presence or absence of residual solvent in microspheres. It should have superior volatile properties, so that it should easily come out from the emulsion leaving hollow microspheres. Commonly used solvents are e.g. ethanol, dichloromethane (DCM), isopropyl alcohol (IPA).

 

4.    Processing medium:

It is used to harden the drug polymer emulsified droplets when the drug polymer solution is poured into it, should not act together with the former, mainly used processing medium are liquid paraffin, polyvinyl alcohol and water.

 

5.    Surfactant:

They are stabilizers and emulsifiers, play the role of hardening the microspheres as well. e.g. tween 80, span 80 and SLS.

 

6.    Cross linking agent:

The cross linking agent such as formaldehyde, glutaraldehyde or by using di acid chlorides such as terephthalogy chloride. The method is inadequate to drugs that do not have any chemical interaction with the cross- linking agent.

 

7.    Hardening agent:

This helps to consolidate the microspheres formed in the processing medium. Most of the hardening agents are as follows.e.g. n-hexane, petroleum ether (in case the processing ordispensation medium is liquid paraffin).

 

      Method of Preparation:

1.    Solvent evaporation method:

The resulting solution is poured into 100 ml of liquid paraffin rotating at 1500rpm. The emulsion is formed and heated at 35C temperature for 3 hrs. After the formation of a stable emulsion, the acetone or dichloromethane is finally evaporated and resulting solidified microspheres is filtered using whattman filter paper. These hollow microspheres impart the floating and sustained properties5.

 

Figure 1: Solvent evaporation method

 

2.    Emulsion solvent diffusion method:

In this method emulsion solvent diffusion, 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 aqueous solvent producing the emulsion droplets even though the organic solvent is miscible.

 

Figure 2: Emulsion solvent diffusion method

 

3.    Solvent diffusion evaporation technique:

This method stirred using propeller agitator for 1-hour evaporation of organic solution and then filtered it. The best formulation is selected on the basis of optimized result of various process variables such as polymer ratio, drug polymer ratio, stirring speed concentration of emulsifier.

 

Figure 3: Solvent diffusion evaporation technique

 

4.    Spray drying:

Spray drying is a process subsequently, a solid shell appears leading toward formation of microspheres.

 

Figure 4: Spray drying

 

      Evaluation of Hollow Microspheres:

1.    Percentage yield:

The percentage yield of the hollow microsphers is determined for drug and is calculated using the following questions.

 

Yield = M/M0 into 100

 

Where

M = Weight of beads

Mo = Total expected weight of drug and polymer8.

 

2.    Micromeritic properties:

Micrometric is a properties of a particle size is determined by an optical microscopy and average diameter of particle is calculated with the help of calibrated ocular micrometer. True density is determined by liquid displacement method; trapped density and compressibility index are calculated by measuring the change in volume using a bulk density apparatus; angel of expose is determined by fixed funnel method.

 

I = vb-vt /vb into 1008.

3.    In vitro buoyancy:

Appropriate quantity of hollow empty microspheres are placed in 900 ml of 0.1 N HCl. The mixture is stirred at 100 rpm for 8-10 hours in dissolution apparatus. After 8 to10 hours, the layers of floating microspheres are pipetted and separated by filtration. Both the fractions of hollow microspheres are weighed. And in vitro buoyancy is determined by the weight ratio of floating microspheres to the sum of floating and sinking microsphers. Buoyancy (%)={wf/(wf+ws)} into 100.

wf and ws are the weights of the floating and settled microspheres12.

 

4.    Scanning electron microscopy:

Dry hollow microspheres are placed on an electron microscope brass stub a coated with gold in a sputter.

 

5.    In -vitro drug release studies:

A weighed amount of hollow microspheres (filled into a hard gelatin capsule) equivalent to dose of drug and place in the basket of dissolution rate apparatus containing dissolution medium. The dissolution fluid is maintained at 371C and rotation speed at a precise rpm.

 

6.    Swelling studies:

Swelling studies are determined by using dissolution apparatus, optical microscopy and other sophisticated techniques, which include H1NMR imaging confocol laser. Scanning microscopy (CLSM). The swelling studies is done using dissolution apparatus.

 

Swelling ratio = weight of wet formulation /weight of formulations.

 

7.    In - vivo studies:

In vivo refers to when research or work is done with or within an entire, living organism. The floating behavior can be investigated by radio graphical studies using barium sulphate microballoons2,4.

 

Applications of Microballoons:

1.    These are filler materials designed as special function additives empty microspheres allow sustained drug release behavior and release the drug over a prolonged period of time.

2.    It is recently described that drugs is to be entrapped in hollow microspheres and reduces the fluctuation included prednisolone, lansoprazole, celecoxib, piroxicam, Theophylline, Aspirin, Griseofulvin, ibuprofen, Terfenadine.

3.    Floating microspheres are site specific drug delivery especially for those drugs which are specifically absorbed from stomach or the proximal part of small intestine.

4.    Empty microspheres of NSAIDS drugs are very successful for controlled release as well as it reduces the side effect of gastric irritation.

5.    Avoidance of gastric irritation because of sustained release effect.

6.    Microsphere morphology allows a controllable variability in degradation and drug release.

 

Advantages:

1.    Drug release in controlled manner for prolonged period.

2.    Hollow microsphers are used to decreases. Material density and gastric retention time is increased because of buoyancy.

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

4.    Site -specific drug delivery to stomach can be achieved microspheres morphology allows a controllable variability in degradation and drug release.

 

DISADVANTAGES:

1.    Controlled - release release formulation generally contains a higher drug load and thus any loss of integrity of the release characteristics of the dosage form may lead to potential toxicity.

2.    Difference in the release rate from one dose to another.

3.    The modified release from the formulations.

4.    Dosage forms of this kind should not be crushed or chewed.

 

Future Potential:

      Exploring the eradication of helicobacter pylori by using various antibiotics.

      Development of various anti-reflux formulation utilizing gastro retentive technologies.

      Design of an array of gastro retentive drug delivery systems, each having narrow GRT for use according to the clinical need. e.g. dosage and state of disease.

 

Table 1: List of Drug Formulated as Microballoons

Drugs

Polymers

Method

Ref

Atenolol

Ethyl cellulose & HPMC

Emulsion solvent evaporation technique

 

8

Captopril

HPMC & Ethyl cellulose

Technique emulsion solvent

 

9

Aceclofenac

Ethyl cellulose

Solvent evaporation

 

10

Metformin

Eudragit RS 100 Eudragit RL

Evaporation

11

Curcumin

Ethyl cellulose, Eudragit S100 & HPMC

Evaporation technique Non-aqueous solvent

 

12

 

Developed once daily sustained release floating dosage form of salbutamol sulfate coated with Eudragit RL 100 using solvent evaporation method and its in vitro characterizations. In vitro drug release studies were carried out in both acidic medium pH 1.2 and pH 6.8 buffers for 12 hours and observed that drug release was faster in pH 6.8 owing to polymer solubility in pH 6.

 

CONCLUSION:

The purpose of this review article on microballoons is to accumulate the recent literature with focus on the development of formulation and applications. We concluded that the micro balloons showed gastro retentive controlled release drug delivery and proved as the most capable drug delivery than conventional drug delivery system.

 

ACKNOWLEDGEMENTS:

We would like to express our thanks to our beloved parents for their blessing. And management of SMBT Sevabhavi trust as well as SMBT Institute of Diploma Pharmacy Dhamangaon, Nashik and wishes for the successful completion of this review article.

 

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10.   Kumar k, Rai AK-Development and evaluation of floating microspheres of curcumin. Tropical Journal of Pharmaceutical Research. 2012; 6(3): 190-197.

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Received on 30.04.2022 Modified on 13.05.2022

Accepted on 20.05.2022 AandV Publications All Right Reserved

Res. J. Pharma. Dosage Forms and Tech.2022; 14(3):233-237.

DOI: 10.52711/0975-4377.2022.00038