international journal of innovative pharmaceutical ...mahammad rafi. shaik department of...
TRANSCRIPT
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 97
SPHERICAL CRYSTALLIZATION – A NOVEL PARTICLE
DESIGN TECHNIQUE FOR SOLUBILITY ENHANCEMENT
1Mahammad Rafi. Shaik*,
2Hajira Abdul Jabbar,
3Kafia Firdouse,
4Renuka,
5T. Rajitha,
6R. Krishna prasad
Department of Pharmaceutics, MAK College of Pharmacy, Chilkoor (V), Moinabad, Greater
Hyderabad, INDIA
Corresponding Author
Mahammad Rafi. Shaik
Department of Pharmaceutics,
MAK College of Pharmacy, Hyderabad, INDIA
Email: [email protected]
Phone: +919700983502
International Journal of Innovative
Pharmaceutical Sciences and Research www.ijipsr.com
Abstract
Direct compression of powders is simple and easy way of making tablets. In direct compression of drugs Good
compressibility and flowability plays a major role. There are several techniques available to impart required
compressibility to drugs. Spherical crystallization methods are very useful methods in which the drug crystals are
modified using different solvents to directly compressible spherical agglomerates, which cost effective and time
saving. Spherical crystallization is a fast developing technique of particle design in which crystallization and
agglomeration can be achieved simultaneously in one step. Spherical crystallization is “An agglomeration process
that changes crystals directly into compact spherical forms during the crystallization process” It is the novel
agglomeration technique that can transform directly as fine crystals produced in the crystallization process into a
spherical shape. Spherical agglomeration, emulsion solvent diffusion and ammonia diffusion method are general
methods in Spherical crystallization. In this spherical crystallization poor solvent, good solvents and bridging
liquid are used. The principle steps involved in the process of spherical crystallization are zero growth zone,
flocculation zone, constant size zone and fast growth zone. Factor controlling the process of agglomeration are
intensity of agitation, solubility profile mode, residence time and temperature of the system. This crystal habit
(form, surface, size and particle size distribution) can be modified during the process of crystallization. The
modifications of such consequences in certain micrometric properties, physicochemical properties (solubility,
dissolution rate, bioavailability and stability) and crystal habit are also modified. Spherical crystallization have
applications in pharmaceuticals like improvement of flowability and compressibility of poor compressible of
drugs, masking bitter taste of drugs and improve the solubility and dissolution rate of poor solublility drugs.
Characterization of spherical crystals determine by optical microscopy, Fourier Transform Infrared spectrometer
(FTIR), Differential scanning calorimeter (DSC).
Keywords: Spherical crystallization, flowability, compactability and agglomeration.
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 98
INTRODUCTION
Tablet is very specific dosage form, accounting for 50% of all oral drug delivery system and 70%
of all pharmaceutical preparation produced. [1] Today the most popular dosage form as Tablets in
all pharmaceutical preparations produced. From the manufacturing point of view tablets can be
produced at much higher rate than any other dosage form. Tablet is the most stable readily
portable and consumed dosage form. [2]. The most popular dosage form (Tablets) of all
pharmaceutical preparations for oral route administration because of easy administration, least
content variations and great accuracy. Along with these advantages, manufacturing of tablets is
most efficient and easy process. flowability and compressibility of materials are important factors
which influences the success of tablets. Direct compressibility is one of the best, economical and
simple techniques for manufacturing of tablets. This facilitates formulation without the moisture,
heat and involves small number of formulating steps. But, the method depends on, the particle
size, flowability, the particle size distribution, bulk density and compressibility of the crystalline
drug substances. Most of the drugs like NSAIDs shows poor flowability and compressibility and
were not suitable for direct compression. For enhancing the flow properties and compressibility of
such drugs several methods have been introduced. Recently pharmaceutical companies are using
modified crystalline techniques for reducing the formulation cost as well as increasing the
production process. Spherical agglomeration is one of the efficient techniques among those. [3].
In 1986, kawashima used the spherical crystallization technique for size enlargement of the drug
in the field of pharmacy. Spherical crystallization was defined by kawashima as “An
agglomeration process that transforms crystals directly in to a compact spherical forms during the
crystallization process.”[4] Spherical crystallization is a particle design technique, by which
crystallization and agglomeration can be carried out simultaneously in one step and which has
been successfully utilized for improvement of flowability and compactability of crystalline drugs.
[5] Presently, particle design techniques are widely used in pharmaceutical industries to modify
primary properties like particle shape, size, crystal habit, crystal form, density, porosity etc. as
well a secondary properties like flow ability, compressibility, compact ability, reduction in air
entrapment, etc Spherical crystallization process transforms the fine crystal obtain during
crystallization into a spherical agglomerates. Agglomerates formed further improves the
flowability and compressibility of pharmaceutical ingredient which enables direct tabletting of
drug instead of further processing like mixing, granulation, sieving, drying etc. There are certain
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 99
parameters which have to be optimized in order to obtain the maximum amount of spherical
crystals. [6]
METHODS OF SPHERICAL CRYSTALLIZATION:-
Quasi emulsion solvent diffusion (QESD):-
It was first mentioned in 1989. This technique was usually applied for the preparation of
microspheres. [7] The drug dissolved in the good solvent (solvent that easily dissolves the
compound to be crystallized), and the solution is dispersed into the poor solvent (an antisolvent
generating the required super saturation), producing emulsion (quasi) droplets, even though the
pure solvents are miscible. The good solvent gradually diffuses out of the emulsion droplets into
the surrounding poor solvent phase, and the poor solvent diffuses into the droplets by which the
drug crystallizes inside the droplets due to the interfacial tension between the two solvents. The
crystallization of the drug occurs by the counter diffusion of the good solvent and poor solvent.
The method is said to be simpler than the SA method, but it can be difficult to find a suitable
additive to keep the system emulsified and to improve the diffusion of the poor solute into the
dispersed phase. At increasing stirring rate the agglomeration was reduced in case of lactose
because of increasing disruptive forces. [8] Higher stirring rate produces agglomerates that are
less porous and more resistant to mechanical stress, and the porosity decreases when the solid
increases. [9] The choice of bridging liquid has an influence on the rate of agglomeration and on
the strength of the agglomerates. In this process, the emulsion is stabilized by the selection of the
suitable polymer which is required for the proper crystallization. In the droplets, the process of
solidification proceeds inwards and the liquid are not maintained on the surface and the
agglomerate formed without coalescence.
Steps involved in QESD method:-
Drug + good solvent
Into poor solvent
Formation of emulsion
(With agitation)
Good solvent which acts as a bridging liquid diffuses out into the poor solvent phase
Formation of spherical agglomerates
Polymeric solution
Stabilized spherical crystal
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 100
Spherical agglomeration:
In spherical agglomeration involve implications of three different solvents. One liquid acts as a
perfect solvent for the drug moiety, second liquid is categorized as antisolvent/poor solvent for
the chemical moiety and third liquid significantly used as bridging liquid should be added in
smaller quantity for promoting the formation of agglomerates. A nearly saturated solution of drug
in good solvent is poured in to the poor solvent, provided that the poor and the good solvents are
freely miscible and affinity between good and poor solvent is stronger than the affinity between
the drug and the good solvent, this leads to the formation of crystals immediately. Further third
solvent called bridging liquid is added in smaller amount to promote the formation of
agglomerates. Under continuous agitation, the bridging liquid is added. The bridging liquid
should not be miscible with the poor solvent and must wet the precipitated crystals. As a result of
interfacial tension effects and capillary forces, the bridging liquid act to adhere the crystals to one
another to form agglomerates. The spherical agglomeration has been applied to several drugs and
it has been found that the product properties are quite sensitive to the amount of bridging liquid.
Relatively less amount of optimum bridging liquid produces plenty of fine crystals and vice versa.
Also the choice of bridging liquid, the starring speed and concentration of solute are of
importance. Higher stirring rate produces agglomerates that are less porous and are more resistant
to mechanical stress, porosity decreases as the concentration of the solid increases.
Ammonium diffusion (AD) method:
In this method, the mixture of three partially immiscible solvent i.e. acetone, ammonia water,
dichloromethane was used as a crystallization system. In this system ammonia water acts as a
bridging liquid as well as good solvent, acetone was the water miscible but a poor solvent, thus
drug precipitated by solvent change without forming ammonium salt. Water immiscible solvent
such as hydrocarbons or halogenated hydrocarbons. [10]
E.g. dichloromethane induced liberation of ammonia water.
This technique usually meant for the amphoteric drugs which cannot be agglomerated by
conventional procedures [11] the whole process is completed in three steps. [12] First the drug
dissolved in ammonia water is precipitated while the droplets collect the crystals. Simultaneously,
ammonia in the agglomerate diffuses to the outer organic solvent. Its ability to act as a bridging
liquid weakens and subsequently spherical agglomerates are formed.
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 101
Steps involved in ammonia diffusion method:
Drug + ammonia water
Added to
Acetone
Dichloromethane added drop wise
Spherical agglomerates
Neutralization technique (NT):
This technique involves the formation of fine crystals by neutralization and consequently their
agglomeration by a bridging liquid. Spherical crystallization of tolbutamide and phenytoin was
reported by this technique. [13] The drug was dissolved in sodium hydroxide solution. Aqueous
solution of hydroxypropyl methylcellulose and hydrochloric acid was added to neutralize sodium
hydroxide solution of tolbutamide, which was then, crystallized out. [14]
Steps involved in neutralization technique (NT):
Drug + good solvent
Added in
Neutralizing solution
Crystallization
Adding bridging liquid
Drop wise
Spherical agglomerates
Traditional crystallization process:
Spherical agglomerates shall be produced in these methods by controlling the physical and
chemical properties and can be called as non typical spherical crystallization processes. [15]
These are salting out precipitation, cooling crystallization, crystallization under melting. Heat
some solvent to boiling. Place the solid to be recrystallized in an Erlenmeyer flask. Pour a small
amount of the hot solvent into the flask containing the solid. Swirl the flask to dissolve the solid.
Place the flask on the steam bath to keep the solution warm. If the solid is still not dissolved in
solution, set it on the bench top. Do not disturb it. After a while, crystals should appear in the
flask. Simultaneously bridging liquid was added drop wise at a definite rate, followed by
crystallization of the crystal form of the drug takes place.
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 102
Solvent change method (SC):
Solvent change method involves simultaneous crystallization and agglomeration of two or more
drugs from a good solvent and bridging liquid by addition of a non-solvent. To obtain fine
crystals the solution of the drug and a good solvent is poured into a poor solvent under controlled
condition of temperature and speed. The bridging liquid is used for agglomeration of the crystals.
The poor solvent has miscibility with good solvent but has low solubility with solvent mixture, so
that, during agitation of the solvent system the crystals are formed. The drawback of this system
is that it provides low yield, due to co-solvency effect of crystallization solvent. The bridging
liquid, the stirring speed and the concentration of the solids are the influencing factors for the
spherical crystallization [16]. Lesser amount of bridging liquid will yield fine particles where as
larger amount of bridging liquid will produce coarse particles. [17] By increasing stirring rate the
agglomeration get reduced because of increasing disruptive forces. [18] Higher stirring rate
produces agglomerates that are less porous and more resistant to mechanical stress. The porosity
decreases when the concentration of the solid increases. [19] The viscosity of the continuous
phase has an effect on the size distribution of the agglomerates. The choice of bridging liquid has
an influence on the rate of agglomeration and also on the strength of the agglomerates.
Steps involved in solvent change method:
Good solvent + drug
In bad solvent
Formation of crystals with addition of bridging liquid (drop wise) and continuous agitation
Precipitated crystals and aggregation with the bridging liquid
Spherical agglomerates
Enlarged spherical agglomerates
Crystallo-co-agglomeration(CCA):
Crystallo-co-agglomeration was invented by kadam and coworkers as an attempt to overcome the
limitations of spherical crystallization techniques, which were restricted to size enlargements of
single high-dose drugs only. Similar to spherical agglomeration, a good solvent is used in this
method to solubilize the drug, the poor solvent to form liquid bridges during the agglomeration
process. CCA is complex process and is influenced by many formulation and process variables.
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 103
Techniques there are two different methods used in spherical crystallization, i.e. typical and non-
typical methods. Non-typical technique is also called as traditional crystallization method which
involves different steps as salting out, cooling and precipitation. The controlling factors are
physical and chemical properties.
Typical technique employs three solvents:
a) Good solvent (dissolution medium).
b) Bridging liquid (partially dissolves the drug and have wetting property).
c) Bad solvent (immiscible with the drug substance).
Spherical agglomeration is a novel agglomeration technique involving agglomerate formation
based on addition of bridging solvent. In typical spherical agglomeration method the drug
dissolved in a good solvent is poured in a poor solvent under controlled condition of agitation
with the addition of bridging solvent which wets the crystal surface to form agglomerate. The
bridging liquid should be immiscible in the suspending medium but capable of cementing the
particles to be agglomerated [20].
Table 1: Different techniques and solvents used in preparing spherical agglomeration of
Drug
Solvent system Drug Good solvent Bad
solvent
Bridging liquid Technique NSAIDS
Aceclofenac [21] Acetone Water Dichloromethane SA Aspirin [22] Acid buffer Methanol Chloroform SA
Acetylsalicyclic acid [23] Ethanol Water Carbon
tetrachloride
SA Celocoxib [24] Acetone Water Chloroform SA Fenbufen [25] THF Water Isopropyl acetate SA
Flubiprofen [26] Acetone Water Hexane SA Ibuprofen [27] Ethanol Water Ethanol SA
Ibuprofen-Paracetamol
[28]
Dichlorometha
ne
Water Dichloromethane CCA Ibuprofen-Talc [29] Dichlorometha
ne
Water Dichloromethane CCA Indomethacin [30] Dimethyl
formamide
Water Chloroform SA
Indomethacin Mepirizole
[31]
Ethyl acetate Water Ethyl acetate CCA Ketoprofen [32] Isopropyl
acetate
Water Choroform SA Ketoprofen-Talc [33] Dichlorometha
ne
Water Dichloromethane CCA Mefenamic acid [34] Ammonia-
water
Acetone Ammonia-water ADM Naproxane [35] Acetone-
ethanol
Water Chloroform SA Nabumetone [36] Ethanol Water Cyclohexane SA
Piroxicam [37] NaOH HCl Chloroform NT Propylphenazone [38] Ethyl alcohol Water Isopropyl acetate SA
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 104
Drug Solvent system Technique
Good solvent Bad solvent Bridging liquid
Antibiotics
Ampicillin Tri
ydrate(ATH) [39]
Ammonia water Acetone Dichloromethane ADM
Cefuroxime Axetil [40] Acetone Water Dichloromethane ESD
Enoxacin [41] Ammonia-water Acetone Ammonia-water ADM
Norfloxacin [42] Ammonia-water Acetone Ammonia-water ADM
Roxythromycin [43] Methanol Water Choroform SA Antihelminthic
Mebandazole [44] Acetone Water Hexane SA
Antiallergic
Tranilast [45] Acetone Water Dichloromethane SA
Antihypertensive
Felodipine [46] Acetone Water Dichloromethane ESD
Antiepileptic
Carbamazepine [47] Ethanol Water Chloroform ESD
Antifungal
Gresiofulvin [48] Dichloromethane Water Dichloromethane ESD
Bronchodialator
Aminophylline [49] Ethanol Water Chloroform SA
Theophylline [50] Ethylene diamine Sod. Chloride Water SA
ß-adrenergic blocker
Acebutalol HCl [51] Ethanol Water Isopropyl acetate ESD
Antidiabetic
Glibenclamide [52] Dichloromethane Water Chloroform SA
Tolbutamine [53] Ethanol Water Isopropyl acetate ESD,NT
Others
Ascorbic acid [54] Water Ethyl Acetate Ethyl Acetate SA,ESD
Aspartic acid [55] Methanol Water - SA
Benzoic acid [56] Ethanol Water Chloroform SA
Bromohexin HCl [57] Dichloromethane Water Dichloromethane CCA
DCP (`Dibasic
calcium Phosphate)
[58]
Citric acid Water Phosphoric acid SA
Valsartan [59] Acetone Water Choroform SA
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 105
SA = Spherical Agglomeration, ESDS = Quasi-Emulsion Solvent Diffusion System, ADS =
Ammonia Diffusion System, NT = Neutralization Technique, CCA = Crystal-co-agglomeration
technique.
REFERENCES
1. Rasmuson CA, katta J. spherical crystallization of benzoic acid. Int. J. pharm, 348, 1997,
61-69.
2. Shangraw RF. Compressed tablets by direct compression. In: Lieberman HA, Lachman L,
Schwartz JB. Pharmaceutical Dosage Forms: Tablets, vol. 1. Marcel dekker, New York,
1989; 195-246
3. Kawashima Y, Handa T, Takeuchi H, Okumura M, Katou H , Nagata O. Crystal
modification of phenytoin with polyethylene glycol for improving the mechanical
strength, dissolution rate and bioavailability by a spherical crystallization technique.
Chem. Pharm. Bull. 1986; 34(8): 3376-3383.
4. Yadav A.V, designing of pharmaceuticals to improve physicochemical properties by
spherical crystallization technique, journal of pharmacy Research Vol.1, Issue 2, Oct-Dec-
2008, 105-112.
5. A.R. Paradkar , A.P. Pawar, K.R. Mahadik, S.S. Kadam. Spherical crystallization: a novel
particle design technique. Indian drugs, 1994, 6: 229-233.
6. Y kawashima. Spherical crystallization as a novel particle design technique for oral drug
delivery system. Chin. Pharm J., 1989, 41:163-172
7. Cui F, Yang M, Jiang Y, Cun D, Lin W, Fan Y, Kawashima Y. Design of sustained-
release nitrendipine microspheres having solid dispersion structure by quasi-emulsion
solvent diffusion method. J. Control. Rel 2003; 91: 375-384.
8. A.S. Bos, F.J. Zuiderweg. Size of agglomerates in batch wise suspension agglomeration.
Chem. Eng .Res. Des., 1987, 65:187
9. A.F. Blandin, D. Mangin, A. Rivoire, J.P. Klein, J.M. Bossoutrot. Agglomeration in
suspension of salicylic acid fine particles: influence of some process parameters on
kinetics and agglomerate final size. Powder Technol., 2003, 130: 316-323.
10. Y. Kawashima, F. Cui, H. Takeuchi, T. Hino, T. Niwa, K. Kiuchi. Parameters
determining the agglomeration behavior and the micrometric properties of spherically
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 106
agglomerated crystals prepared by spherical crystallization technique with miscible
solvent system. Int J. Pharm., 1995, 119:139-147.
11. Hector GP, Jorge B, Carlo A. Preparation of norfolxacin spherical agglomerates using
the ammonium diffusion system. J. Pharm. Sci. 1998; 87(4): 519-523.
12. Ueda M, Nakamura Y, Makita H, Imasato Y, kawashima Y. particle design of enoxacin by
spherical crystallization technique. I principle of ammonium diffusion system (ADS).
Chem. Pharm.Bull.1990; 38 (9): 2537-2541.
13. Sano A, Kuriki T, kawashima Y, Takeuchi Hino T, Niwa T, Particle design of the
tolbutamide by the spherical crystallization technique III micrometric properties and
dissolution rate of tolbutamide spherical agglomerates produced by quasi-emulsion
diffusion method, Chem. Pharm. Bull. 1990; 38: 733-739.
14. A. Sano, T. Kuriki, Y. Kawashima, H. Takeuchi, T. Hino, T. Niwa. Particle design of
tolbutamide by the spherical crystallization technique IV, improved of dissolution and
bioavailability of direct compression tablets prepared using Tolbutamide agglomerated
crystals Chem Pharm Bull., 1992, 40: 3030-3035.
15. Narendra Kr. Goyal, Nitin Sharma, P.K. Sharma. Spherical crystallization: a method for
improving tablet and powder characteristics. Der pharmacia lettre, 2010, 2(4): 246-25.
16. Mudit dixit,p.k. Kulkarni, P Subhash Chandra Bose, Rami reddy. Spherical agglomeration
of indomethacin by solvent change method. IJPRD.2010, 2(9), 33.43.
17. A Bausch, H. Leuenberger. Wet spherical agglomeration of proteins as a new method to
prepare parentral fast soluble drug forms. Int J Pharm.1994;101:63-70
18. A.S. Bos,F.J. Zuiderweg, Size of agglomerates in batch wise suspension agglomeration.
Chem Eng Res Des. 1987; 65a:187.
19. A.F. Blandin, D. Mangin, A. Rivoire, J.P. Klein, JM Bossoutrot. Agglomeration in
suspension of salicylic acid fine particles: influence of some process parameters on
kinetics and agglomerate final size. Powder Technol.2003; 130: 316-323.
20. Mahanty S., Sruti J., Niranjan C., RaoM., “Particle design of drugs by spherical
crystallization techniques.” Int .j. of pharmaceutical sci. and Nanotech. 2010, 3(2), 912-
918.
21. Usha AN, Mutalik S, Reddy MS, Ranjith AK, Kushtagi P, Udupa N. Preparation
and in-vitro preclinical and clinical studies of aceclofenac spherical agglomerates. Eur
J Pharm Biopharm. 2008; 70, 674-683.
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 107
22. M.C. Deshpande, KR Mahadik, AP Pawar, AR Paradkar. Ind J Pharm Sci. 1997; 59 (1),
32-34.
23. H. Goczo, R.P. Szabo, M. HasznosNezdei, Chem Pharm Bulletin. 2000; 48(12), 1877-
81.
24. V.R. Gupta, M. Srinivas, M.M. Patel, G.K. Jani. Acta Pharm. 2007; 57, 173-184.
25. P.D. Martino, C. Barthelemy, F. Piva, E. Joiris, C. Marthelemy. Drug Dev. Ind. Pharm.
1999; 25 (10), 1073-1081.
26. M.K. Chourasia, S.K. Jain, N.K. Jain. Ind. Jr. Pharm. Sci. 2003; May-June, 287-291.
27. Y. Kawashima, T. Niwa, T. Handa, H. Takeuchi, T. Iwamoto. J Pharm Sci. 1989; 78(1),
68-72.
28. Mahadik KR, Pawar AP, Paradkar AR, Kadam S. Crystallo-co-agglomeration: A Novel
Technique to obtain Ibuprofen-Paracetamol Agglomerates. AAPS Pharm SciTech.2004.
5 (3), 1-8.
29. Pawar A, Paradkar A, Kadam S, Mahadik K. Agglomeration of Ibuprofen with Talc
by Novel Crystallo-Co- Agglomeration Technique. AAPS PharmSci Tech. 2004; 5(4),
1-6.
30. Mudit Dixit*, P. K. Kulkarni1, Spherical agglomeration o f Indomethacin by solvent
change method International Journal of Pharma Research and Development 2005; 2(9),
33-43.
31. Kawashima Y. Development of spherical crystallization technique and its application
to pharmaceutical systems. Arch Pharm. Res. 1984; 7(2), pp 145-151.
32. Mudit dixit*, Dr.P. K. Kulkarni and Ashwini G Kini Spherical agglomeration of
Ketoprofen by solvent change method International Journal of Pharmaceutical Sciences
Review and Research 2010;4(3), pp 129-135.
33. Chavda V, Maheshwari RK. Tailoring of ketoprofen particle morphology via novel
crystallo-coagglomeration technique to obtain a directly compressible material. Asian J.
Pharm. 2008; 2(1), pp 61-67.
34. Agrawal GP, Bhadra S, Kumar M, Jain S, Agrawal S. Spherical Crystallization of
Mefenamic Acid. Pharm. Tech. Feb-2004, 66-76.
35. Maghsoodi M, Hassan-Zadeh D,Barzegar-Jalali M, Nokhodchi A and Martin G.
Improved Compaction and Packing Properties of Naproxen Agglomerated Crystals
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 108
Obtained by Spherical Crystallization Technique. Drug Dev. Ind. Pharm 2007; 33,
1216-1224.
36. C.L. Viswanathan, S.K. Kulkarni, D.R. Kolwankar. AAPS Pharm Sci Tech 2006; 7 (2),
Article 48.
37. M. Dixit, .P. K. Kulkarni Preparation and characterization of spherical agglomerates
of Piroxicam by neutralization method American journal of drug discovery and
development 2011, 1-12.
38. Di Martino P, Di Cristofaro R, Barthélémy C, Joiris E, Palmieri FG, Sante M.
Improved compression properties of propyl phenazone spherical crystals. Int. J.
Pharm. 2000; 197 (1-2), 95-106.
39. Gohle MC, Parikh RK, Shen H, Rubey RR. Improvement in flowability and
compressibility of Ampicilline Trihydrate by spherical crystallization. Ind J Pharm Sci.
2003, 634-37.
40. Yadav VB, Yadav AV. Polymeric Recrystallized Agglomerates of Cefuroxime Axetil
Prepared by Emulsion Solvent Diffusion Technique. Trop. J. Pharm. Res. 2009; 8(4),
361-369.
41. Ueda M, Nakamura Y, Makita H, Imasato Y, Kawashima Y. Particle design of
Enoxacin by spherical crystallization technique. Chem. Pharm. Bulletin. 1990; 38 (9),
2537-2541.
42. Hector GP, Jorge B, Carlo A. Preparation of Norfloxacin spherical agglomerates using
the ammonia diffusion system. J. Pharm. Sci. 1998; 87(4), 519-523.
43. Bermer GG, Zuiderweg FG. Proceedings of international symposium of fine particles.
AIME, New York. 1992, 1524-46.
44. Kumar S, Chawla G, Bansal A. Spherical Crystallization of Mebendazole to Improve
Process ability. Pharm. Dev. Technol. 2008; 13(6), 559-568.
45. Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y, Furuyama S, Characterization of
polymorphs of Tranilast anhydrate and Tranilast monohydrate when crystallization by
two solvents changes spherical crystallization technique , J. Pharm. Sci. 1991;80(5),
472-78.
46. Amit R. Tapas, Pravin S. Kawtikwar Polymeric recrystallized spherical
agglomerates of felodipine by quasi-emulsion solvent diffusion method Pelagia
Research Library Der Pharmacia Sinica 2010; 1(1), 136- 146.
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 109
47. Nokhodchi A, Maghsoodi M, Hassanzadeh D. An Improvement of Physicomechanical
Properties of Carbamazepine Crystals. Iran. J. Pharm. Res. 2007 6(2), 83-93.
48. Yadav VB, Yadav AV. Effect of Different Stabilizers and Polymers on Spherical
Agglomerates of Gresiofulvine by Emulsion Solvent Diffusion (ESD) System. Int. J.
Pharm. Tech. Res. 2009; 1(2), 149-150.
49. Kawashima Y, Aoki S, Takenaka H, Miyake Y. Preparation of spherically agglomerated
crystals of Aminophylline. J. Pharm Sci 1984; 73(10), 1407-1410.
50. Kawashima Y. Development of spherical crystallization technique and its application
to pharmaceutical systems. Arch Pharm. Res. 1984; 7(2), 145-151.
51. Kawashima Y, Cui F, Takeuchi H, Niwa T, Hino T, Kiuchi K . Parameters
determining the agglomeration behavior and the micromeritic properties of spherically
agglomerated crystals prepared by the spherical crystallization technique with miscible
solvent systems Int. J. Pharm. 1995; 119(2), 139-147.
52. Vinay K. Mishra, Sumeet Dwivedi Method development for spherical crystallization of
glibenclamide and evaluation of micromeritic properties Drug Invention Today 2010; 2
(2), 119-122.
53. Sano A, Kuriki T, Kawashima Y, Takeuchi H, Hino T, Niwa T. Particle design of
Tolbutamide by the spherical crystallization technique IV, Improved of dissolution and
bioavailability of direct compression tablets prepared using Tolbutamide agglomerated
crystals, Chem. Pharm. Bull. 1992; 40, 3030-3035.
54. . Kawashima Y, Imai M, Takeuchi H, Yamamoto H, Kamiya K. Development of
agglomerated crystals of Ascorbic acid by the spherical crystallization techniques.
Powder Technol. 2003; 130, 283– 289.
55. Szabo-Revesz P, Goczo H, Pintye-Hodi K, Kasa P and Eros I, M. Hasznos-Nezdei M,
Farkas B. Development of spherical crystal agglomerate of an aspartic acid salt for
direct tablet making. Powder Technol. 2011; 114, 118–124.
56. Rasmuson CA, Katta J. Spherical crystallization of benzoic acid. Int. J. Pharm. 2008;
348, 61-69.
57. Paradkar A, Jadhav N, Pawar A. Design and Evaluation of Deformable Talc
Agglomerates Prepared by Crystallo-Co-Agglomeration Technique for Generating
Heterogeneous Matrix. AAPS PharmSciTech. 2007; 8(3), 1-7.
58. Takami K, Machimura H, Takado K, Inagaki M, Kawashima Y. Novel preparation of
REVIEW ARTICLE Mahammad et.al / IJIPSR / 3 (2), 2015, 97-110
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com February Issue 110
free flowing spherically agglomerated dibasic calcium phosphate anhydrous for direct
tabletting. Chem Pharm Bulletin. 1996; 44(4), 686-870.
59. Miss Bhosale Bhakti Bhimarao, Mr. D. M. Shivale Preparation and characterization
of spherical crystals of Valsartan for direct compression method International journal
of Pharma Research and Development March 2009;1 Article-4.