Tailoring of ketoprofen particle morphology via novel crystallocoagglomeration technique to obtain a directly compressible material

Main Article Content

Vikash Chavda
Rajesh Kumar Maheshwari


Purpose: The purpose of this research was to develop a novel crystallo-co-agglomeration (CCA) method for ketoprofen to obtain its directly compressible spherical agglomerates with improved flowability and compressibility.
Methodology: Dichloromethane-water system containing polyethylene glycol (PEG) 6000, polyvinyl alcohol (PVA), and hydroxypropylmethylcellulose (HPMC) 100 Centi Poise was used as the crystallization system. Ketoprofen was crystallized from dichloromethane and agglomerated with talc. Experimental parameters (concentration of PEG, PVA, and HPMC; effect of temperature; and agitation speed) were optimized. The agglomerates were evaluated for micrometric properties, mechanical properties, moisture content, compressibility, packability, and drug-release properties. The agglomerates were
characterized by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), infrared (IR) spectroscopy, and scanning electron microscopy (SEM). Main Findings: Remarkable improvement in micromeritic properties (angle of repose <22°, percentage compressibility <10, and Hausner ratio near to 1) and compactibility (mean yield pressure 55-93 MPa) enabled direct compression without any defect. Results of friability showed higher surface strength of agglomerates containing higher amount of talc. DSC, PXRD, and IR results showed no change in the crystalline form of ketoprofen. Dissolution study
of batches KA, KB, KC, and KD(composition given in Table 1) showed 90% drug release in 120, 180, 240, and 420 min respectively. Principal Conclusions: Crystallo-co-agglomeration process can be considered as a suitable alternative to
conventional granulation process to obtain agglomerates of ketoprofen with improved micromeritic and compressibility parameters. The CCA technique can be used for the design of sustained-release ketoprofen talc agglomerates containing
lower amounts of polymers.


Download data is not yet available.

Article Details

How to Cite
Chavda, V., & Maheshwari, R. K. (2014). Tailoring of ketoprofen particle morphology via novel crystallocoagglomeration technique to obtain a directly compressible material. Asian Journal of Pharmaceutics (AJP), 2(1). https://doi.org/10.22377/ajp.v2i1.177


Nicholasm G, Frampton CS. Physicochemical characterization of the

orthorhombic polymorph of paracetamol crystallized from solution.

J Pharm Sci 1998;87:684-93.

Alsaidan SM, Abdulhakeem AA, Eshra AG. Improved dissolution rate of

indomethacin by adsorbents, Drug Dev Ind Pharm 1998;24:389-94.

Wang H, Zhang R. Compaction behavior of paracetamol powders of

different crystal shapes. Drug Dev Ind Pharm 1995;21:863-8.

Kawashima Y, Okumara M, Takenaka H. The effect of temperature on the spherical crystallization of salicylic acid. Powder Technol 1984;39:41-7.

Paradkar AR, Pawar AP, Chordiya JK, Patil VB, Ketkar AR. Spherical

crystallization of celecoxib. Drug Dev Ind Pharm 2002;28:1213-20.

Kawashima Y, Aoki S, Takenama H, Miyake Y. Preparation of spherically

agglomerated crystals of aminophylline. J Pharm Sci 1984;73:1407-9.

Kawashima Y, Cui F, Takeuchi H, Niwa T, Hino T, Kiuchi K. Improvement

in flowability and compressibility of pharmaceutical crystals for direct

tableting by spherical crystallization with a two solvent system. Powder

Technol 1994;78:151-6.

Ueda M, Nakamura Y, Makita H, Kawashima Y. Preparation of micro-

capsules masking the bitter taste of enoxacin by using one continuous

process of agglomeration and microencapsulation. J Microencapsul


Kawashima Y, Lin SY, Naito M, Takenama H. Direct agglomeration of

sodium theophylline crystals produced by salting out in liquid. Chem

Pharm Bull 1982;30:1837-43.

Kadam SS, Mahadik KR, Paradkar AR, inventors. A process for making

agglomerates for use as or in a drug delivery system. Indian patent

February 14, 1997.

Kadam SS, Mahadik KR, Paradkar AR. Inventors: A process for making

agglomerates for use as or in a drug delivery system. Indian patent

February 14, 1997.

Pawar AP, Paradkar AR, Kadam SS, Mahadik KR. Agglomeration of

ibuprofen with talc by novel crystallo-co-agglomeration technique,

AAPS PharmSciTech 52004, E55.

Pawar AP, Paradkar AR, Kadam SS, Mahadik KR. Crystallo-co-

agglomeration: A novel process to obtain ibuprofen-paracetamol

agglomerates, AAPS PharmSciTech 2004;5:E44.

Jadhav N, Pawar A, Paradkar A. Design and evaluation of deformable

talc agglomerates prepared by crystallo-co-agglomeration technique for

generating heterogeneous matrix. AAPS PharmSciTech 2007;8:E1-7.

Martin A, Swarbrick J, Cammarata A. Physical pharmacy, 3rd ed, Mumbai: KM Varghese Co; 1991. p. 497-500.

Vela MT, Fernandez AM, Rabasco AM. Rheological study of lactose

coated with acrylic resins. Drug Dev Ind Pharm 1990;16:295-300.

Lachman L, Lieberman HA, Kanig JL., The Theory and Practice of

Industrial Pharmacy, 2nd ed. Fourth Indian Reprint. Mumbai: Varghese

Publishing House; 1991. p. 184.

Jaros PJ, Parrot EJ. Comparison of granule strength and tablet strength. J Pharm Sci 1983;72:530-5.

Pawar PH, Pawar AP, Mahadik KR, Paradkar AR. Evaluation of tableting

properties of agglomerates obtained by spherical crystallization of

trimethoprim. Indian J Pharm Sci 1998;60:24-8.

Heckel RW. Density-pressure relationships in powder compaction. Trans

Mettall Soc AIME 1961;221:671-5.

Heckel RW. An analysis of powder compaction phenomena. Trans Mettall

Soc AIME 1961;221:1001-8.

Martino PD, Cristofara RD, Barthelemy C, Joiris E, Filippo GP, Sante M.

Improved compression properties of propyphenazone spherical

crystals. Int J Pharm 2000;197:95-106.

Kawashima Y, Imai M, Takeuchi H, Yamamoto H, Kamiya K, Hino T.

Improved flowability and compactibility of spherically agglomerated

crystals of ascorbic acid for direct tabletting designed by spherical

crystallization. Process Powder Technol 2003;130:283-9.

Niwa T, Takeuchi H, Hino T, Itoh A, Kawashima Y, Kiuchi K. Preparation

of agglomerated crystals for direct tabletting and microencapsulation

by the spherical crystallization technique with a continuous system.

Pharm Res 1994;11:478-84.