This document discusses microspheres, including their definition, classification, preparation methods, evaluation, applications, and marketed preparations. Microspheres are spherical particles between 1-1000 μm in size that can be made of polymers, proteins, or synthetic materials. Common preparation methods include single/double emulsion, solvent evaporation, phase separation coacervation, spray drying, and polymerization. Microspheres are evaluated based on particle size, drug entrapment efficiency, swelling index, and in vitro drug release. They have applications in oral, nasal, ocular, and transdermal drug delivery due to their ability to provide sustained release and target drug delivery.

1. MICROSPHERES:
PREPARATION AND EVALUATIONS
Submitted By: Prachi Pandey*, Rahul Pal Submitted To: Mr. Arsh Chanana
M. Pharm (Pharmaceutics), IInd Sem.
Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University, Jaipur, Rajasthan.
Microparticles are particles between 0.1 and
100 μm in size. Commercially available
microparticles are available in a wide variety of
materials including ceramics, glass, polymers,
and metals.

2. DEFINITION
 Microspheres are small spherical particles, with diameter
1 µm to 1000 µm.
 They are spherical free flowing particles consisting of
proteins or synthetic polymers which are biodegradable in
nature.
Microspheres representation

3.  Microcapsules are those in which entrapped substance is distinctly surrounded by distinct capsule wall.
 Micrometrics in which entrapped substance is dispersed throughout the matrix.
CLASSIFICATION OF MICROSPHERES

4. CLASSIFICATION
Microspheres and Microcapsules Representation

5. MICROSPHERE TYPES
Types Description Application
Bio-adhesive Microsphere Prolong residence time Nasal Gentamycin
Floating Microsphere Bulk density less than gastric fluid NSAIDs, Antibiotics
Radioactive Microsphere Deliver high radiating dose to
target site
Diagnostics: Liver, spleen
Polymeric Microsphere Biodegredable and non-
biodegredable swells in aq media
Vaccine: Hepatitis
Local: Proteins
Magnetic Microsphere Localize the drug to release site Chemotherapeutics agents to liver

6.  Improve bioavailability.
 Provide constant and prolonged therapeutic effect.
 Provide constant drug concentration in blood.
 Decrease dose and toxicity.
 Protect the drug from enzymatic and photolytic cleavage so it is best for drug delivery of protein.
 Reduce the dosing frequency and thereby improve the patient compliance
ADVANTAGES

7. DISADVANTAGE
 The cost is more.
 Reproducibility is less.
 Process conditions like change in temperature, pH, solvent addition, and evaporation/agitation may
influence the stability of core particles.
 Degradation of product due to heat, hydrolysis, oxidation, solar radiation or biological agents.

8. MARKETED PREPARATION OF
MICROSPHERES
Marketed Formulations of Microspheres
BRAND NAME COMPANY DRUG APPLICATION
Protonix® Wyeth
Pharmaceutical
Germany
Pantaprazole Gastric Ulcer
Altinac® Janssen Cilag
Pharmaceutical inc.
Tritinoin Skin regeneration
Lumason® Bracco Diagnostics
inc.
Sulfa Hexafluoride
lipid microsphere
Diagnosis and
Investigation

9.  Single Emulsion Technique
 Double Emulsion Technique
 Solvent Evaporation
 Phase Separation Coacervation Technique
 Spray Drying and Spray Congealing
 Solvent Extraction
 Polymerization
METHODS OF PREPARATION

10. SINGLE EMULSION TECHNIQUE
Polymers in Aqueous Solution
Disperse in Organic Phase ( Oil/Chloroform)
Stir / Sonicate
Chemical crosslinking or heat denaturation
Microsphere in Organic Phase
Microsphere

11. DOUBLE EMULSION METHOD
Polymer in aqueous solution with drug
Disperse in organic phase
First Emulsion (W/O)
Multiple Emulsion
Microsphere in solution
Microsphere
Homogenization or sonication
Addition of Aqueous solution PVA
Addition of large aqueous solution
Separate , dry, wash

12. SOLVENT EVAPORATION
Core Material
Coating Polymer Solution
Core material disperse in liquid manufacturing vehical
phase
Evaporation of polymer solvent
Microsphere
Disperse
Agitate
Evaporate

13. PHASE SEPARATION COACERVATION
TECHNIQUE
Aquous / Organic solution in polymer
Drug disperse in polymer solution
Polymer rich globules
Microsphere in aquous / organic
phase
Microsphere
Add Drug
Phase separation induced by different means
Solidify
Separate, dry, wash

14. SPRAY DRYING / SPRAY CONGEALING
Polymer disperse in organic phase (acetone)
Drug disperse in polymer solution with high speed
homogenization
Atomizes in steam of hot air
Formation of small droplets
Microsphere
Solvent Evaporation

15. SPRAY DRYING / SPRAY CONGEALING
Polymer disperse in organic phase (acetone)
Coating Polymer Solution
Core material disperse in liquid manufacturing vehical
phase
Evaporation of polymer solvent
Microsphere
Separation by cyclone separator and drying by vacuum
drying

16. SOLVENT EXTRACTION

17. POLYMERIZATION

18. BULK POLYMERIZATION

19. SUSPENSION POLYMERIZATION

20. EMULSION POLYMERIZATION

21. INTERFACIAL POLYMERIZATION

22.  1) Particle size and shape: The most widely used
procedures to visualize microparticles are conventional
light microscopy (LM) and scanning electron microscopy
(SEM).
 2) Degradation behavior: The surface chemistry of the
microspheres can be determined using the electron
spectroscopy for chemical analysis (ESCA).
EVALUATION

23.  3) Angle of repose: The powder mass was allowed to flow
through the funnel orifice kept vertically to a plane paper
kept on the horizontal surface, giving a heap angle of
powder on paper. The angle of repose was calculated by
the following equation
tan ϕ =h/r
 Where, h & r are the height band radius of the powder
cone.
EVALUATION

24. EVALUATION
 4) Bulk density: Bulk density was obtained by dividing the mass
of powder by the bulk volume in cm³. It was calculated by using
equation;
Bulk density volume = Mass of microspheres / Bulk
 5) Tapped density: It is the ratio of total mass of the powder to
the tapped volume of the powder. It is expressed in g/ml.
Tapped Density = Mass of the microspheres (W) / Tapped Volume of the
microspheres (Vf)
Density Apparatus

25. EVALUATION
 6) Drug entrapment efficiency: It is the percentage of
drug that is successfully entrapped with in microspheres
 Drug entrapment efficiency can be calculated using
following equation
% Entrapment = Actual content / Theoretical content x
100

26. EVALUATION
 7) Swelling Index :
 It is conducted in a phosphate buffer of pH 6.8. Their
diameter is measured periodically by using laser
particle size distribution analyzer until they were
decreased by erosion and dissolution.
Swelling index= (mass of swollen microspheres -
mass of dry microspheres/mass of dried
microspheres) 100

27. EVALUATION
 8) In-Vitro methods:
 Release studies for different type of microspheres are carried out by
using phosphate buffer pH 7.4, mostly by rotating paddle apparatus.
 Agitated with 100 rpm, samples were collected at specific time intervals
and replaced by same amount and analyzed.
Dissolution Apparatus

28. EVALUATION
 9) Adhesion property:
 Freshly cut piece of pig intestine is used (5 cm long),clean and
wash it with isotonic saline solution.
 Accurate weight of microspheres was placed on mucosal surface,
phosphate buffer of pH 6.8 is warmed at 37 °c was peristaltically
pumped at a rate of 5 ml/min over the tissue.
 The duration of complete washing microspheres from pig intestine
was recorded.

29. APPLICATIONS
 Ophthalmic Drug Delivery
 Oral drug delivery
 Gene delivery (RISPERDAL CONTRA risperidone)
 Nasal drug delivery
 Buccal drug delivery
 Gastrointestinal drug delivery
 Transdermal drug delivery (TDDS)
 Prostate Cancer
 Opoids craving reducer (VIVITROL naltrexone)

30. REFERENCE
1. https://www.amazon.com/Microspheres-Microcapsules-Biotechnology-Preparation-
Applications/dp/9814316474
2. Dhadde, Gurunath S., et al. "A review on microspheres: Types, method of preparation, characterization and
application." Asian Journal of Pharmacy and Technology” 11.2 (2021): 149-155.
3. Vasava, Drashti, Jitendra Patel, and Umesh Upadhyay. "A review article on: Microsphere." National
Journal of Pharmaceutical Sciences 2.2 (2022): 148-154.