A Review on Floating Microsphere

Amuge Vilas, S.S. Siddheshwar

Pravara Rural College of Pharmacy, Pravaranagar A/P Loni – 413736, Tal – Rahata, Dist. – Ahmednagar.

*Corresponding Author E-mail: vilasamuge1@gmail.com

ABSTRACT:

The purpose of floating microsphere's is to improve gastric retention time. The Floating drug delivery systems are lower in the bulk thickness than the gastric juice and remain floating on gastric juice for long period of time without impacting gastric-emptying rate and increasing the bioavailability. The Gastro-retentive microspheres can particularly suitable for continuous and late release of the oral formulations with blending versatility to achieve the various release patterns, low dose risk as the reproducible and short gastric retention time. Ths gastric emptying is a complex process, one that is very highly variable and it makes in vivo performance of the drug delivery systems uncertain. The controlled drug delivery system with prolonged residence time in stomach can be of great practical importance for the drugs with absorption window in upper small intestine. The main limitations can attributed to inter- and intra-subject variability of the gastro intestinal (GI) transit time and to non-uniformity of the drug absorption throughout the alimentary canal. The floating or hydro dynamically controlled drug delivery systems are useful in such applications. Various gastro retentive dosage forms are available, including tablets, pills, laminated films, floating microspheres, capsules, granules and the powders. The floating microspheres (Hollow Microspheres) are the gastro-retentive drug delivery systems based on non-effervescent approach. Hollow microspheres are in strict sense, spherical empty particles without core, free flowing powders consisting of proteins or synthetic polymers, ideally having a size in the range 1-1000 micro meter. Gastro-retentive floating microspheres 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.

KEYWORDS: Microsphere, Gastro retentive, Hydrogels, Floating drug delivery system.

INTRODUCTION:

Among the different routes of the drug administration, oral route has achieved the most attention, partly due to ease of the administration and to important flexibility in the dosage form design¹.

The primary aim of the oral controlled drug delivery is most preferable route of the drug delivery system is to achieve the better bioavailability and release of drug from the system which should be reproducible and
predictable, easy for administration, patient compliances and flexibility in formulation for the effective therapy or to improve therapeutic efficiency of the drug through improved bioavailability. The gastro retentive dosage forms significantly extend for period of time, over which drug may be released and thus prolong dosing intervals and increase patient compliance. The gastric retention can be achieved by mechanism of mucoadhesive or bioadhesion systems, high density systems, magnetic systems, expansion system, super porous hydrogels, raft forming systems, low density system and the floating ion exchange resins.¹

1. In most of cases, the important variability of gastrointestinal tract physiology and its transit time leads to the unpredictable bioavailability and the nonreproducible therapeutic effects. One requisite for the successful performance of the oral controlled release drug delivery systems is the drug should have good absorption throughout gastrointestinal tract (GIT)².

2. The Floating drug delivery is intended to hold drug in the stomach and ideal for drugs with poor solubility and low intestinal fluid stability on basis that FDDS makes the dosage type less dense than the gastric fluid to allow it swim on them. Without impacting rate of gastric emptying. The drugs with shorter half-lives that are readily absorbed in GIT are highly removed from circulation of the serum. To resolve these difficulties, oral managed drug delivery mechanism has been risen as they release the drug into the GIT for longer periods of time and retain a steady concentration of the medication in the serum. In the gastric area, gastro retentive dosage type may last for few hours and thus significantly increase drug GRT to improve bioavailability, minimize the drug waste and improve the solubility of drugs with the low solubility. Floating microspheres are empty spherical particles without a center, inthe strict sense. With free-flowing particles ranging from 1 to 1000μm.³

Recent advances in the novel drug delivery system to enhance safety and efficacy of drug molecule by formulating a dosage form being convenient for the administration. The high level of the patient compliance has been observed in taking oral dosage forms is due to ease of administration and handling of these forms. There are lot of advancements have seen in the oral controlled drug delivery system in last few decades, this system has been of limited success in the case of the drugs with a poor absorption window throughout the GIT .To modify GIT time is one of main challenge in the development of the oral controlled drug delivery system.⁴

Fig 1: Anatomy of Stomach

Factors affecting floating microsphere:

The Gastric residence time of an oral dosage form is affected by the several factors. In order to pass through pyloric valve into the small intestine, the particle size should be within the range of 1 to 2mm. The pH of the stomach in fasting state is about ~1.5 to 2.0 and in fed state it is 2.0 to 6.0. he large volume of water administered with an oral dosage form raises the pH of stomach contents above 4. The stomach does not have time to produce sufficient acid when the liquid empties stomach, hence the basic drugs generally have a better chance of dissolving in the fed state than in fasting state.

The alcohol and opioids reduce rate of gastric empting, as do pain, fear, and anxiety (it acting via sympathetic nervous system which inhibits motility). Anti muscarinics, e.g., atropine, glycopyrrolate, also increase the gastric emptying time. Metoclopramide, a prokinetic drug.

The resting volume of stomach is about 25 to 50ml. The Volume of the liquids administered affects gastric emptying time. When volume is large, the emptying is faster. Fluids taken at body temperature leave stomach faster than the colder or warmer fluids. The Studies have revealed that gastric emptying of the dosage form in the fed state can also be influenced by its size. The Small-sized tablets leave stomach during the digestive phase, while large-sized tablets are emptied during housekeeping waves. The above data is again supported by study carried out by Rhie et al. (1998). They have found smaller pellets (0.7mm) emptying during the fed state and larger pellets (3.6mm) emptying during fasted state. Various gastric emptying times were observed for the non-disintegrating tablets of different sizes. The longest gastric emptying time was observed for 13mm tablets (171±13min), followed by 11mm tablets (128± 17min) and 7mm tablets (116±19min) (Khosla, Davis, 1990).

ADVANTAGES OF FDDS :

· Enhanced bioavailability

· Targeted therapy for the local ailments in upper GIT

· Sustained drug delivery reduced frequency of the dosing

· Reduced counter-activity of body

· Extended effective concentration.

· Minimized adverse activity at colon

· Improved selectivity in the receptor activation

· Reduced fluctuations of drug concentration.⁷

DISADVANTAGES OF FDDS:

· The drug substances that are unstable in acidic environment of stomach are not suitable candidates to be incorporated in systems. These systems require a high level of the fluid in the stomach for drug delivery to float and work efficiently.

· Not suitable for the drugs that have solubility or stability problem in GIT.

· These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently.

· Not suitable for drugs that have solubility or stability problem in GIT.

· Drugs such as nifedipine which is well absorbed along the entire GIT and which undergoes first pass metabolism, may not be desirable.

· Drugs which are irritant to gastric mucosa are also not suitable.

· The drug substances that are unstable in the acidic environment of the stomach are not suitable candidates to be incorporated in the systems.

· The dosage form should be administered with a full glass of water (200-250 ml).⁷

MECHANISM OF FLOATING MICROSPHERE :⁴

When the microspheres come in the contact with gastric fluid, gel formers, polysaccharides, and the polymers hydrate to form a colloidal gel barrier that controls rate of fluid penetration into device and the drug release. As exterior surface of the dosage form dissolves, the gel layer is maintained by hydration of the adjacent hydrocolloid layer. The air trapped by swollen polymer lowers density and confers buoyancy to microspheres. However, a minimal gastric content is needed to allow the proper achievement of buoyancy. They communicate with acid in stomach after administration of dosage type, since outer layer of the floating microspheres includes the polysaccharides and polymer.

Mechanism of drug release form microspheres following method .

1. Erosion

2. Diffusion

3. Osmosis

2. Ionic gelation method:

Ionotropic gelation is based ability of poly electrolytes to cross link in presence of the counter ions to form beads. Since, use of alginates, gellan gum, chitosan and the carboxymethyl cellulose for encapsulation of drug and even cells, ionotropic gelation technique has been used for this purpose.

3. Double emulsion technique:

The double-emulsion method used for preparation of microspheres involves formation of the double or multiple emulsions of water and oil. This method can be used with both natural and the synthetic polymers. The aqueous drug solution is dispersed in the lipophilic organic continuous phase.

4. Phase separation co-acervation technique:

In this method, drug particles are dispersed in the solution of polymer and an incompatible polymer is added to system which makes first polymer to phase separate and engulf the drug particles. Addition of non-solvent results in solidification of a polymer. The agglomeration must be avoided by stirring suspension using a suitable speed stirrer since as process of microspheres formation begins the formed polymerize globules start to stick and form the agg⁴.

5. Single emulsion technique:

In this method, the micro particulate carriers of the natural polymers i.e. those of proteins and the carbohydrates are prepared by single emulsion technique. The natural polymers are dissolved or dispersed in the aqueous medium followed by dispersion in non-aqueous medium like oil with help of cross linking agent.²

6. Quasi emulsion solvent diffusion:

Microsponges can be manufactured by a quasiemulsion solvent diffusion method using the external phase containing distilled water and polyvinyl alcohol. The internal phase consists of drug, ethanol, and the polymer. At first, internal phase is manufactured at 60ºC and then added to external phase at room temperature.

CHARACTERIZATION OF FLOATING MICROSPHERE:

Particle size:

Size is the measured using an optical microscope, and mean particle size is calculated by measuring 200–300 particles with help of a calibrated ocular micrometer. Different sizes of the microspheres and their distribution in each batch are measured by sieving the mechanical shaker, using a nest of standard sieves (ASTM) and shaking period of 15 minutes. Particle size distribution is determined and mean particle size of microspheres is calculated by using following formula¹.

Mean particle size = ∑(mean particle size of the fraction× weight fraction)/∑(weight fraction)

Tapped density:

The tapping method can be used to calculate the tapped densities. The volume of weighed quantity of the microspheres was determined after 100 taps as well as 1000 taps using tapped density apparatus.²

Tapped density = sample weight/sample volume

Density of bulk:

Density of Bulk Bulk density is defined as powder mass divided by the density of the bulk. (Expressed in gm/cm³). The Bulk Density = Sample Weight/Sample Volume⁶.

Compressibility index:

Tapped density – Bulk density

% Compressibility Index = ------------------------- x 100

Tapped density

Hausners ratio:

Tapped density

Housner ratio= --------------------------------------

Bulk density

Angle of repose:

The maximum angle which is formed between surface of a pile of powder and the horizontal surface is called the angle of repose.⁴

Tan Ө = h / r

Where Ө = angle of repose

h = height of the circle formed by the powder heap

r = radius of heap

APPLICATIONS:

· Delivery of site specific drugs

· Drug delivery sustained

· As a transporter

· Maintaining constant blood level

· Enhancement for absorption⁶.

CONCLUSION:

From the review paper we had concluded that, drug absorption in gastrointestinal tract is a highly variable procedure and prolonging gastric retention of dosage form extends the time for the drug absorption. As a competent strategy for increasing the bioavailability and regulated delivery of the various beneficial agents, the floating microspheres have emerged. Major worldwide efforts have been made to discover these systems, both in terms of the therapeutic efficacy and compliance, which meet patient needs.

REFERENCE:

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2. Jagtap Yogesh Mukund, Bhujbal Rohan Kantilal, Ranpise Nisharani Sudhakar. Floating microsphere: a review. Brazillian Journal of Pharmaceutical Sciences. 2012; 48: 17.

3. Gayatridevi M. J. Adlin Jino Nesalin, T. Tamizh Mani. Floating microsphere: A Review. International Journal of Research in Pharmacy and Chemistry. 2016; 501.

4. T.S. Shinde, A.N. Barate. A Review on Floating Microsphere. International Journal of Pharmaceutical and Biological Science. 2019; 7: 87.

5. Fmith Celvia Miranda, Krishnananda Kamath. Floating Microsphere: A Review. World Journal of Pharmacy and Pharmaceutical Sciences. 2019; 8: 379.

6. https://www.slideshare.net/shireenzeba/floating-drug-delivery-system-ppt

7. https://www.slideshare.net/DivyaThakur17/microspheres-67311278.

Received on 07.10.2023 Modified on 05.12.2023

Asian J. Pharm. Tech. 2024; 14(1):31-35.

DOI: 10.52711/2231-5713.2024.00007