Approaches to Creating and Past Successful Attempts on Microspheres: A Primer for Aspiring Researchers


Kappala Sailaja, Hindustan Abdul Ahad, Haranath Chinthaginjala, Renuka Gudisipalli,

Sugali Indravath Rajyalakshmi, Yamuna Vagganagari

Department of Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research

(RIPER) - Autonomous, K.R. Palli Cross, Chiyyedu (P), Ananthapuramu - 515721, AP, India.

*Corresponding Author E-mail:



The work was aimed at the gathering and projection of literature on microspheres. A targeted drug delivery system is intended to increase the concentration of medication in the areas of interest while reducing its concentration in the rest of the body. Thus, the drug is localized at the target site. It does not affect the surrounding tissues. Carriers have therefore proven to be a useful approach to drug delivery since the drug is coupled with a carrier particle such as microspheres, nanoparticles, liposomes, niosomes, and so on, that controls the release and absorption of the drug. A microsphere is a free-flowing powder consisting of proteins or synthetic polymers that are biodegradable in nature and, ideally, have a particle size of under 200 m. If it is modified, it is a reliable way to deliver the drug to the target site with high specificity and to maintain the desired concentration without unintended side effects. As a result of their long-term release, microspheres have been receiving a lot of attention, especially for their ability to target anticancer drugs to the tumor. By combining microspheres with a variety of other strategies, microspheres will have a key role in the delivery of pharmaceuticals, especially in diseased cell sorting, diagnostics, gene delivery, and safe, targeted, and effective in vivo delivery. This article will help research to get a quick reference to the past work done on microsphere dosage forms.


KEYWORDS: Delivery, microspheres, release, review, target.




In the novel drug delivery system, a drug is delivered at a rate determined by the needs of the body during the duration of treatment, and its active ingredients are delivered to the site of action. Currently, no drug delivery system can fulfill all the lofty goals, however, sincere efforts are being made to achieve them through novel approaches to drug delivery1.


Different routes of administration are available for controlled and targeted drug delivery, resulting in a variety of novel drug delivery systems. In recent years, there has been considerable interest in using microspheres for drug delivery2. In terms of sustained or controlled release, microspheres of biodegradable and nonbiodegradable polymers have been studied. Microspheres are characterized by a microphase separation morphology, which acts as a catalyst to control degradation rate and drug release3.


Methods for preparation of microspheres:

The following techniques were adopted in making microspheres4,5:

1. Single emulsion techniques

2. Double emulsification techniques

3. Polymerization

    a. Normal polymerization

·     Bulk

·     Suspension

·     Emulsion

    b. Inter-facial polymerization

4. Coacervation phase septation technique

5. Spray drying and spray congealing technique

6. Solvent evaporation method

7. Solution- strengthening distribution method

8. Wax coating and Hot-melt method


Pharmaceutical application of microspheres

The main inputs of microspheres in pharma field are as follows6.

·      Vaccine delivery

·      Monoclonal antibodies

·      Imaging

·      Topical porous microsphere

·      Nasal drug delivery

·      Oral drug delivery

·      Targeting drug delivery

·      Gastro-retentive controlled delivery system

·      Bio-medical applications

·      Pharmaceutical application


Advantages of microspheres:

Microspheres have these merits7

·      Microspheres show constant and long-lasting therapeutic action.

·      Dosing frequency can be changed, and so we can improve patient compliance.

·      Due to their spherical shape and smaller size, they could be injected into the body.

·      good bioavailability and low risk of side effects

·      Microsphere morphology all depends on controllable variability in degradation and drug release.


Disadvantages of microspheres:

The demerits of microspheres are as follows8

·      The modified release from the formulations

·      The release rate of the controlled release dosage form may vary due to a variety of factors, like food and the rate of transit through the gut.

·      differences in the release rate from one dose to another.

·      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.

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


For quick reference to the researchers who want to work on microspheres, Table 1 summarizes previous successful attempts on microspheres.


Table 1: Past work done on drugs and polymers in making microspheres





Poly lactic acid (PLA)

9Juni et al., 1985

Diclofenac sodium


10Hideshi et al., 1990

5-fluro uracil

PLA, and Polyglycolide (PGA)

11Moritera et al., 1991


Poly anhydride (PA)

12Bhagat etal., 1994


Gelatin, poly glycolic acid-co-DL-lactic acid (PGLA)

13Habib et al., 1999



14Kwak et al., 2000



15Dinarvand et al., 2003

Metaprolol tartrate

Egg albumin, ethyl cellulose (EC), and Eudragit RL 100

16Rajinikanth et al., 2003

Cyclosporin A


17B Malaekeh et al., 2005


Chitosan, and Pectin

18Orhan et al., 2006


Mucuna gum

19Amaechi et al., 2007


Polyethylene glycol 600

20Nappinnai et al., 2007


Poly lactic acid

21Im et al., 2008

Ketorolac tromethamine

Polycaprolactone (PCL), and PLA

22Sinha et al., 2008



23Sankavarapu et al., 2009

Theophylline, xanthine derivative


24Jelvehgari et al., 2010


Bovine serum albumin

25Parashar et al., 2010



26Chandiran et al., 2010



27Swapna et al., 2010


EC, and HPMC

28Ganesh et al., 2010


Carboxy Methyl Cellulose

29Arya et al., 2010



30Venkatesan et al., 2011


Chitosan, sodium alginate, and egg albumin

31Jelvehgari et al., 2011

Tetanus toxoid


32Arthanari et al., 2011


Bovine serum albumin

33Malviya et al., 2011



34Sibeko et al., 2012


poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), and PLA

35Bazzo et al., 2012

Ropinirole HCl


36Madan et al., 2013



37Gokhale et al., 2013

Enalapril maleate

Egg albumin

38Nanjwade et al., 2014



39Reddy et al., 2014


Hydroxyethyl methacrylate (HEMA)

40Jafari et al., 2015



41Guan et al., 2015.


Egg albumin, EC, and Eudragit L 100

42Bose et al., 2016

Mefenamic acid

Ethyl cellulose

43Anusha et al., 2016

Venlafaxine HCl


44Jain et al., 2016



45Ni et al., 2016



46Masaeli et al., 2016


chitosan-graft-polyacrylamide (CS-g-PAM)

47Bulut et al., 2016


Olibanum gum, Guar gum (GG), and sodium alginate

48Pandey et al., 2016



49Kenechukwu et al., 2016

Losartan potassium


50Khairnar et al., 2017


Xanthan gum, and GG

51Bhattacharjee et al., 2018

Ivabradine HCl (IBH)

Egg albumin, and EC

52Singh et al., 2019

Metformin hydrochloride 

Khaya gum, and sodium alginate

53Ozoude et al., 2020



54Jabar et al., 2021


Carbopol 934, chitosan and sodium alginate

55Palanivelu et al., 2021



Microsphere has the advantage of target specificity and better patient compliance compared to many other types of drug delivery systems. From the foregoing, it is concluded that microspheres are a promising candidate for sustained and targeted drug delivery in various targeted organs. Aside from drug delivery, microspheres are also used for imaging tumors, detecting biomolecule interactions for diagnostics, and cancer treatment, among other things. Therefore, in the future, microspheres will play a very important role in the advancement of medicine. Researchers will be provided with a quick reference to past literature on microspheres through this review.



The authors are thankful to the college management for the encouragement and the support.



1.     Jwalapuram R, Ahad HA, Haranath C, Thadipatri R, Varshitha CV, Kumar YB. A desktop reference to the solubility enhancement of drugs with the aid of surfactants. (2020). Int. J. Life Sci. Pharma Res.;11(5): P11-16.

2.     Ahad HA, Haranath C, Rahul Raghav D, Gowthami M, Naga Jyothi V, Sravanthi P. Overview on Recent Optimization Techniques in Gastro Retentive Microcapsules by Factorial Design. Int J Pharm Sci Res. 2019;10(9):247-54.

3.     Ahad HA, Chinthaginjala H, Rahamtulla S, Pallavi BP, Shashanka C, Prathyusha J. A Comprehensive report on Solid Dispersions by Factorial Design. Asian Journal of Research in Chemistry. 2021 Aug 3;14(4):297-301.

4.     Harsha SS, Ahad HA, Haranath C, Dasari RR, Gowthami M, Varam NJ, Musa GB. Exfoliation Technique of Composing and Depictions of Clopidogrel Bisulphate Afloat Microspheres. Journal of Evolution of Medical and Dental Sciences. 2020 Apr 6;9(14):1156-61.

5.     Ahad HA, Sreenivasulu R, Mallapu Rani E, Reddy BV. Preparation and evaluation of famotidine high density gastro retentive microspheres with synthetic and natural polymers. Journal of Pharmaceutical Education & Research. 2011 Jun 1;2(1).

6.     Ahad HA, Reddy BK, Ishaq BM, Kumar CH, Kumar CS. Fabrication, and in vitro evaluation of glibenclamide Abelmoschus esculentus fruit mucilage-controlled release matrix tablets. J Pharm Res. 2010;3(5):943-6.

7.     Ahad HA, Kumar BP, Haranath C, Reddy KS. Fabrication and evaluation of glimepiride Cordia dichotoma G. Forst fruit mucilage sustained release matrix tablets. Int J Chem Sci. 2009;7(4):2555-60.

8.     Ahad HA, Yesupadam P, Guruprakash P, Sravanthi M, Ramyasree P. Phytochemical, and hypoglycemic evaluation of Alangium salviifolium root extract. Journal of Scientific Research. 2011 Apr 28;3(2):393-402.

9.     Juni K, Ogata J, Nakano M, Ichihara T, Mori K, Akagi M. Preparation, and evaluation in vitro and in vivo of polylactic acid microspheres containing doxorubicin. Chemical and pharmaceutical bulletin. 1985 Jan 25;33(1):313-8.

10.   Hideshi N, Kenji S, Kazuhiko J, Yasunori M, Toshikatsu S, Sigeru F. Preparation, and evaluation of biodegradable albumin microspheres containing mitomycin C. International journal of pharmaceutics. 1990 Jan 15;58(1):79-87

11.   Moritera T, Ogura Y, Honda Y, Wada R, Hyon SH, Ikada Y. Microspheres of biodegradable polymers as a drug-delivery system in the vitreous. Investigative ophthalmology & visual science. 1991 May 1;32(6):1785-90.

12.   Bhagat HR, Hollenbeck RG, Pande PG, Bogdansky S, Fait CD, Rock M. Preparation, and evaluation of methotrexate-loaded biodegradable polyanhydride microspheres. Drug development and industrial pharmacy. 1994 Jan 1;20(10):1725-37.

13.   Habib M. Preparation and characterization of ofloxacin microspheres for the eradication of bone associated bacterial biofilm. Journal of microencapsulation. 1999 Jan 1;16(1):27-37.

14.   Kwak SH, Hwang SJ, Lee BC. Preparation and Evaluation of Bupivacaine Microspheres by a Solvent Evaporation Method. Yakhak Hoeji. 2000;44(6):511-20.

15.   Dinarvand R, Moghadam SH, Mohammadyari-Fard L, Atyabi F. Preparation of biodegradable microspheres and matrix devices containing naltrexone. Aaps Pharmscitech. 2003 Sep;4(3):45-54.

16.   Rajinikanth P, Sankar C, Mishra B. Sodium alginate microspheres of metoprolol tartrate for intranasal systemic delivery: development and evaluation. Drug delivery. 2003 Jan 1;10(1):21-8.

17.   B Malaekeh, N., SA Sajadi, T. and MR, J., 2005. Preparation of biodegradable microspheres encapsulated with Cyclosporine A and evaluation of some factors affecting microsphene properties.

18.   Orhan Z, Cevher E, Mülazimoglu L, Gürcan D, Alper M, Araman A, Özsoy Y. The preparation of ciprofloxacin hydrochloride-loaded chitosan and pectin microspheres: their evaluation in an animal osteomyelitis model. The Journal of bone and joint surgery. British volume. 2006 Feb;88(2):270-5.

19.   Amaechiattama AN, Nwabunze OJ. Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation. Acta Pharmaceutica. 2007 Jun 1;57(2):161-71.

20.   Nappinnai M, Kishore VS. Formulation and evaluation of microspheres of diltiazem hydrochloride. Indian journal of pharmaceutical Sciences. 2007;69(4):511.

21.   Im JS, Oh DH, Li DX, Sung JH, Yoo BK, Kim J, Woo JS, Lee YB, Kim SM, Choi HG, Yong CS. Preparation and Evaluation of Meloxicam-loaded Poly (D, L-lactic acid) Microspheres. Journal of Pharmaceutical Investigation. 2008;38(1):63-72.

22.   Sinha VR, Trehan A. Development, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres as a depot system for parenteral delivery. Drug delivery. 2008 Jan 1;15(6):365-72.

23.   Sankavarapu V, Aukunuru J. Preparation, characterization, and evaluation of hepatoprotective activity of NNDMAC biodegradable parenteral sustained release microspheres. Asian Journal of Pharmaceutical Research and Health Care. 2009;1(2):240-59.

24.   Jelvehgari M, Barar J, Valizadeh H, heydari N. Preparation and evaluation of poly (ε-caprolactone) nanoparticles-in-microparticles by W/O/W emulsion method. Iranian Journal of Basic Medical Sciences

2010; 13 (3): 85-96.

25.   Parashar V, Ahmad D, Gupta SP, Upmanyu N, Parashar N, Mudgal V. Formulation, and evaluation of biodegradable microspheres of tinidazole. International Journal of Drug Delivery. 2010 Jul 1;2(3): 238-241.

26.   Chandiran IS, Sivakumar T, Kumar BP. Preparation, and evaluation of aceclofenac loaded biodegradable microspheres. Int J Pharm Biomed Res. 2010;1(1):19-23.

27.   Swapna N, Jithan AV. Preparation, Characterization in vivo Evaluation of Parenteral Sustained Release Microsphere Formulation of Zopiclone. Journal of Young Pharmacists. 2010 Jul 1;2(3):223-8.

28.   Ganesh S, Kumar DS, Kumar BS, Abhilash R, Bharadwaj PS, Raj KV, Mohammed I, Pravalika T. Controlled release formulation and evaluation of idarubicin microsphere using biodegradable hydrophilic and hydrophobic polymer mixtures. Asian J Pharm Clin Res. 2010;3(3):179-82.

29.   Arya RK, Singh R, Juyal V. Mucoadhesive microspheres of famotidine: preparation characterization and in vitro evaluation. International Journal of Engineering science and technology. 2010;2(6):1575-80.

30.   Venkatesan P, Manavalan R, Valliappan K. Preparation, and evaluation of sustained release loxoprofen loaded microspheres. Journal of basic and clinical pharmacy. 2011 Jun;2(3):159.

31.   Jelvehgari M, Barar J, Valizadeh H, Shadrou S, Nokhodchi A. Formulation, characterization, and in vitro evaluation of theophylline-loaded Eudragit RS 100 microspheres prepared by an emulsion-solvent diffusion/evaporation technique. Pharmaceutical development and technology. 2011 Dec 1;16(6):637-44

32.   Arthanari S, Renukadevi P, Mani KR. Preparation, and evaluation of sucrose stabilized tetanus toxoid encapsulated into chitosan microspheres. Genomic Medicine, Biomarkers, and Health Sciences. 2011 Sep 1;3(3-4):91-7.

33.   Malviya R, Singh A, Singh PK, Sharma PK. Formulation development and evaluation of magnetic microspheres containing caffeine as model drug. Int J Pharm Res Technol. 2011;3(1):1-2.

34.   Sibeko B, Choonara YE, du Toit LC, Modi G, Naidoo D, Khan RA, Kumar P, Ndesendo VM, Iyuke SE, Pillay V. Composite polylactic-methacrylic acid copolymer nanoparticles for the delivery of methotrexate. Journal of drug delivery. 2012 Jul 5; 579629.

35.   Bazzo GC, Macedo AT, Crenca JP, Silva VE, Pereira EM, Zétola M, Pezzini BR. Microspheres prepared with biodegradable PHBV and PLA polymers as prolonged-release system for ibuprofen: in vitro drug release and in vivo evaluation. Brazilian Journal of Pharmaceutical Sciences. 2012 Dec;48(4):773-80.

36.   Madan J, Kadam V, Bandavane S, Dua K. Formulation, and evaluation of microspheres containing ropinirole hydrochloride using biodegradable polymers. Asian journal of pharmaceutics. 2013 Jan 1; 7 (4): 184 - 188

37.   Gokhale KS, Jonnalagadda S. Preparation and evaluation of sustained release infliximab microspheres. PDA journal of pharmaceutical science and technology. 2013 May 1;67(3):255-66.

38.   Nanjwade BK, Patel UD, Kadam VT, Idris NF, Srichana T. Formulation, and evaluation of enalapril maleate biodegradable microspheres. Journal of Pharmaceutical Sciences and Pharmacology. 2014 Sep 1;1(3):200-10.

39.   Reddy AS, Sailaja AK. Preparation and characterisation of aspirin loaded ethylcellulose nanoparticles by solvent evaporation technique. World Journal of Pharmaceutical Sciences. 2014 Apr 8; 3:1781-93.

40.   Jafari M, Kaffashi B. Preparation, and In vitro Evaluation of Isoniazid-Containing Dex-HEMA-Co-PNIPAAm Nanogels. Ciência e Natura. 2015 Dec 21; 37:55-62.

41.   Guan Q, Chen W, Hu X. Development of lovastatin-loaded poly (lactic acid) microspheres for sustained oral delivery: in vitro and ex vivo evaluation. Drug design, development, and therapy. 2015; 9:791.

42.   Bose PS, Nagaraju R, Saritha D, Padmasri B, Reddy PS. Preparation and evaluation of indomethacin loaded alginate microspheres. Ceska a Slovenska farmacie: casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti. 2016 Jan 1;65(3):104-10.

43.   Anusha K, Krishna SA. Preparation and evaluation of mefenamic acid loaded microspheres using synthetic and natural polymers. Der Pharmacia Lettre. 2016;8(1):197-205.

44.   Jain S, Datta M. Montmorillonite-alginate microspheres as a delivery vehicle for oral extended release of venlafaxine hydrochloride. Journal of Drug Delivery Science and Technology. 2016 Jun 1; 33:149-56.

45.   Ni Q, Chen W, Tong L, Cao J, Ji C. Preparation of novel biodegradable ropivacaine microspheres and evaluation of their efficacy in sciatic nerve block in mice. Drug design, development, and therapy. 2016; 10:2499.

46.   Masaeli R, Kashi TS, Dinarvand R, Tahriri M, Rakhshan V, Esfandyari-Manesh M. Preparation, characterization, and evaluation of drug release properties of simvastatin-loaded PLGA microspheres. Iranian journal of pharmaceutical research: IJPR. 2016;15(Suppl): 205–211.

47.   Bulut E. Controlled delivery of the popular nonsteroidal anti-inflammatory drug, paracetamol, from chitosan-g-polyacrylamide microspheres prepared by the emulsion crosslinking technique. Artificial cells, nanomedicine, and biotechnology. 2016 Aug 17;44(6):1482-90.

48.   Pandey N, Sah NA, Mahara K. Formulation and evaluation of floating microspheres of nateglinide. International Journal of Pharma Sciences and Research. 2016;7(11):453-64.

49.   Kenechukwu FC, Momoh MA. Formulation, characterization, and evaluation of the effect of polymer concentration on the release behavior of insulin-loaded Eudragit®-entrapped mucoadhesive microspheres. International journal of pharmaceutical investigation. 2016 Apr;6(2):69.

50.   Khairnar G, Naik J, Mokale V. A statistical study on the development of micro particulate sustained drug delivery system for Losartan potassium by 32 factorial design approach. Bulletin of Faculty of Pharmacy, Cairo University. 2017 Jun 1;55(1):19-29.

51.   Bhattacharjee S, Dutta G, Guha N, Banerjee D, Roy T, Maiti S. Formulation and Evaluation Study of Azithromycin Tablets by Various Natural Polymers and their Comparative Preformulation Study. Research Journal of Pharmacy and Technology. 2018;11(3):1107-11.

52.   Singh P, Mani TT, Goswami S, Singh P. Comparative evaluation of ivabradine hydrochloride loaded natural and synthetic microspheres 2019; 4(1): 368-379

53.   Ozoude CH, Azubuike CP, Ologunagba MO, Tonuewa SS, Igwilo CI. Formulation and development of metformin-loaded microspheres using Khaya senegalensis (Meliaceae) gum as co-polymer. Future Journal of Pharmaceutical Sciences. 2020 Dec;6(1):120.

54.   Jabar A, Madni A, Bashir S, Tahir N, Usman F, Rahim MA, Jan N, Shah H, Khan A, Khan S. Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization. Plos one. 2021 Apr 30;16(4): e0250876.

55.   Palanivelu M, Prashob A, Ramalingam N, Muniyandi SK. Formulation and Evaluation of Ranitidine Hydrochloride Loaded Floating Microspheres for the Treatment of Gastric Ulcer. International Journal of Current Science Research and Review, 2021; 4(8), 833-845.





Received on 03.02.2022        Modified on 18.02.2022

Accepted on 27.02.2022   ©AandV Publications All Right Reserved

Res.  J. Pharma. Dosage Forms and Tech.2022; 14(3):245-248.

DOI: 10.52711/0975-4377.2022.00040