INTRODUCTION:

There are different novel drug delivery carriers like microspheres, nanoparticles, nano capsules, liposomes, phytosomes, nano emulsions, ethosomes and transferosomes are available for herbal formulations. Main advantages of novel herbal formulation are less toxicity, improved solubility, enhancement of bioavailability, protection from degradation, controlled drug release, improved stability and better therapeutic efficiency.

Bacterial infections in skin:

Most of the people in the universe are suffering from bacterial skin infections. This is one of the common problems which encountered in the clinical practice. The bacterial skin infections which caused by the bacteria, mainly the gram positive and gram negative bacteria¹.

The gram positive bacteria which includes Staphylococcus aureus A and B, Streptococcus viridans and Enterococcus faecalis.

The gram negative bacteria that which effect very less that are Capnocytophaga species, Haemophilus influenza, Pasteurella multocida, Mycobacterium species, Proteus species, Pseudomonas species and other anaerobes. Staphylococcus aureas, one of major species in bacteria which mainly causes the bacterial skin infections². Styphylocccus aureus and streptococcus pyrogens are the commonly recognized sources of skin infections.

Nair A et.al studied skin and soft tissue infections (SSTIs) are mainly caused by Staphylococcus aureus and streptococcus pyogens. SSTIs are caused by methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistance is common for both community-associated (CA)-MRSA and health associated (HA)-MRSA infections³.

Herbal medicines for the treatment of bacterial infections in skin:

In the current years, our medicinal practices were largely dominated by plant based medicines. In the contrast, many developing nations continued to benefit from the rich knowledge of medicinal herbalism. The various advantages of herbal medicines are lesser side effects, low cost, wide spread availability and effectives with chronic conditions. Kulkarni GT et.al studied that plant based drugs are used for many ailments but is having some stability issues and also poor lipid solubility. So that in order to overcome these problems herbal novel drug delivery system for phytomedicines have emerged. Herbal novel drug delivery system includes liposomes, phytosomes, ethosomes, transferosomes and particulate delivery systems includes microspheres, micropellets, nanoparticles and micro - nano emulsions. When herbal drugs incorporated to this system it improved stability, bioavailability and reduce toxicity⁴. Thillaivanan S et.al, conducted the study regarding the constraints, opportunities and challenges regarding the herbal medicines. In developing and developed countries, the herbal medicine is used widely in past years. According to the studies the herbal medicines have lesser side effects when compared to the conventional medicines⁵.

Microspheres:

Microspheres are very small spherical particles, which is having diameter in the micrometer range mostly 1μm -1000μm⁶. Natural polymers and synthetic polymers are used for the preparation of microspheres. In microspheres, drugs are dispersed as crystalline or finely divided form⁷.

Figure 1. Classification of microspheres.

Types of Microspheres

1 Bio adhesive microspheres

2 Magnetic microspheres

3 Radioactive microspheres

4 Floating microspheres

5 Polymeric microspheres

a) Biodegradable polymeric microspheres

b) Synthetic polymeric microspheres

1. Bio adhesive microspheres:

Bio adhesive microspheres, it will adhere to the mucosal membrane such as ocular, rectal, buccal etc. This adhesion is due to the sticking property of polymer⁸. In these types of microspheres produces better and enhanced therapeutic efficiency due to its prolonged contact at the site of application⁹.

2. Magnetic microspheres:

This is another important class of microspheres because it localizes drug towards the disease site¹⁰. In this, there are many magnetic carriers which will receive magnetic responses to magnetic field from the incorporated materials¹¹. In this only less amount of drug is required, because magnetically targeted drugs are used¹².

3. Radioactive microspheres:

These types of microspheres are more effective in case of tumors. After injecting in to the arteries, the radioactive microspheres exactly located into cancerous tissue and deliver the radiation without affecting the normal tissues¹³.

4. Floating microspheres:

The bulk density of floating microspheres is less than that of gastric fluid so that it will float in stomach. In this type, drugs are given as floating microspheres and it is having prolonged therapeutic effect¹⁴. In these types of microspheres showed enhanced gastric residence time due to its floating nature and slow drug release. Another advantage of floating microspheres is reduced dose dumping¹⁵.

5. Polymeric microspheres:

It can be classified into two

a) Biodegradable polymeric microspheres:

Starch is biodegradable as well as bio adhesive in nature. Here microspheres showed high residence time due to its prolonged contact with the mucous membrane¹⁶. They will easily convert to gel form because of its swelling nature in water. The main disadvantage of degradable polymer microspheres are low drug loading efficiency and drug release is difficult to control^17.18.

b) Synthetic polymeric microspheres:

It is mostly used as fillers, drug delivery vehicles etc. and it’s having wide clinical applications but in these types of microspheres, it is having chances of moving away from the site of injection and leads to embolism, organ damage etc¹⁹.

Ideal Characteristics of Microspheres:

· It should incorporate reasonably high concentration of drug.

· Controlled particle size and solubility in aqueous vehicles for injection.

· Biocompatibility with a controllable biodegradability.

· It should be stable with satisfactory shelf life.

· Control release of the drug over long period.

General Methods of Preparation of Microspheres:

1. Spray Drying:

In this polymer is dissolved in suitable solvents such as acetone, dichloromethane etc²⁰. Solid form of drug then dispersed in the above solution by the help of high-speed homogenization and atomized in hot air. After atomization, solvent evaporates it will results in the formation of small droplets (1-100μm). During this procedure, traces of solvent can be removed by vacuum drying and micro particles are removed by using cyclone separator²¹.

2. Solvent evaporation:

Solvent evaporation is mainly carried out in liquid vehicle phase and this microcapsule coating will dispersed in the volatile solvent²². For microencapsulation, core material is dispersed in coating polymer solution. The core material is dissolved in liquid manufacturing vehicle phase to get particular size of microcapsule^23,24. Core materials are of two types i.e., water soluble as well as water insoluble materials, if core is soluble in polymer solution then it is matrix type microcapsule. Solvent evaporation is the one of the method which widely used in the preparation of microspheres²⁵.

3. Single emulsion techniques:

The process involves dissolving of natural polymers in aqueous phase and then dispersion is transferred in to a non aqueous phase and finally cross linking of dispersed globule will occur. The cross linking can occur either by chemical cross linkers or by heat²⁶. Chemical cross linkers such as formaldehyde are used for heat sensitive substances. But drawback of chemical cross linker is that more exposure of chemicals to the active pharmaceutical ingredients at the time of manufacturing²⁷.

4. Double emulsion techniques:

In this technique, multiple emulsion of type w/o/w is formed. This techniques most useful in case of water soluble drugs, proteins, peptides, vaccines, etc. Here both natural and synthetic polymers can be used²⁸.

5. Phase separation coacervation technique:

In this method, coacervates are formed. Coacervates are polymer rich phase formed by decreasing solubility of polymer in the organic phase. Here incompatible polymer is added to the solution of polymer, where the drug particles are dispersed in it and non-solvent is added for solidification of polymer. In this process, the formation of coacervates determines rate of polymer film distribution, particle size etc. The agglomerates are avoided using high speed stirring and this will results in microsphere formation²⁹.

6. Spray drying and spray congealing:

In this method, polymers are dissolved in suitable volatile organic solvent such as acetone, dichloromethane. Under high speed homogenization, the drug is then dispersed in polymer solution. This dispersion is atomized in a steam of hot air. This will results the formation of the small droplets due to atomization¹⁷.

7. Solvent Extraction:

This method is used in manufacturing of microspheres. In this method, organic phase is removed by means of extraction with non-aqueous solvent. Here water miscible organic solvent such as isopropanol is used mainly³⁰. In this process, the holding time for microspheres decreases. The organic phase can be easily removed by extraction with water. The one and only difference of this process is direct incorporation of drug or protein to polymer organic solution¹⁸. The solvent removal rate by this process depends on temperature, solubility profile of polymers and ratio of emulsion volume to the water ¹⁹.

8. Quassi emulsion solvent diffusion:

This method is used for the manufacturing of micro sponges and controlled release microspheres. Controlled release microspheres are usually prepared with acrylic polymer³¹. It consists of two phases. Internal phase is prepared at 60⁰C. Here external phase is added to internal phase at room temperature. Then stirred for 2 h after formation of emulsion and then filtered to separate micro sponges, then it is washed and dried in vacuum²⁰.

General Applications^{21, 22, 23}

· The solubility of poorly soluble drug can be increased by means of particle size reduction.

· It provides prolonged therapeutic effect and decreases toxicity.

· Constant drug concentration in blood can be achieved.

· It prevents the drug from photolytic and enzymatic cleavage so it is found to be the best for the drug delivery of proteins.

· It helps to mask the unpleasant taste by converting liquid to solid form.

· Can delay volatilization.

· Use for ophthalmic, nasal, buccal, gastrointestinal, transdermal, colonic, vaginal drug delivery

Evaluation of Microspheres:

1. Particle shape and size:

It is usually observed by means of scanning electron microscopy (SEM)^12,32.

2. Density determination:

Density of microsphere is determined by using multi volume pycnometer¹³.

3. Isoelectric point:

Isoelectric point is determined by micro electrophoresis and the electrophoretic mobility of microspheres is measured during this process ^14,33.

4. Swelling index:

It can be calculated from the following formula,

Swelling index = *100.

5. Drug entrapment efficiency:

It is calculated by using the following formula³⁴,

% entrapment = ×100

CONCLUSION :

This review highlighted the importance of microspheres as a novel drug delivery carrier for plant extracts for antibacterial activity. The herbal drugs can be in cooperated to the microspheres for the better release of the drug and also better entrapment efficiency which in turn enhances the therapeutic efficiency

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Received on 10.11.2017 Modified on 13.12.2017

Research J. Pharm. and Tech 2018; 11(4):1681-1684.

DOI: 10.5958/0974-360X.2018.00313.X