Abstract
The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration (CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical agglomerates containing ∼95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc governed the drug release rate. The batch containing a higher proportion of talc showed zeroorder kinetics and drug release was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with talc as an excipient.
Keywords: ibuprofen, talc, crystallo-co-agglomeration, miniscular drug form, drug release retardation
Full Text
The Full Text of this article is available as a PDF (278.5 KB).
References
- 1.Lovgren K, Lundberg PJ. Determination of sphericity of pellets prepared by extrusion/spheronization and the impact of some process parameters. Drug Dev Ind Pharm. 1989;14–15:2375–2392. doi: 10.3109/03639048909052536. [DOI] [Google Scholar]
- 2.Gokonda SR, Hileman GA, Upadrastha SM. Development of matrix controlled release beads by extrusion-spheronization techniques technology using a statistical screening design. Drug Dev Ind Pharm. 1994;20:279–292. doi: 10.3109/03639049409050183. [DOI] [Google Scholar]
- 3.Hideji O, Kiyoji K, Masayuki H, Takao G, Chikanori T. inventors. Ibuprofen-containing granule: its preparation, and internal medicine comprising it. JP patent 56-120616. Nov. 22, 1981.
- 4.Paradkar AR, Maheshwari M, Ketkar AR, Chauhan B. Preparation and evaluation of ibuprofen beads by melt solidification technique. Int J Pharm. 2003;255:33–42. doi: 10.1016/S0378-5173(03)00081-4. [DOI] [PubMed] [Google Scholar]
- 5.Paradkar AR, Maheshwari M, Tygi AK, Chauhan B, Kadam SS. Preparation and characterization of flurbiprofen beads by melt solidification technique. AAPS PharmSciTech. 2003;4(4):E65–E65. doi: 10.1208/pt040465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Schaefer T, Holm P, Kristensen HG. Melt granulation in a laboratory scale high shear mixer. Drug Dev Ind Pharm. 1990;16:1249–1277. doi: 10.3109/03639049009115960. [DOI] [Google Scholar]
- 7.Johansen A, Schaefer T, Kristensen HG. Evaluation of melt agglomeration properties of polyethylene glycols using a mixer torque rheometer. Int J Pharm. 1999;183:155–164. doi: 10.1016/S0378-5173(99)00093-9. [DOI] [PubMed] [Google Scholar]
- 8.White JL, Szdlowski W, Min K, Kim MH. Twin screw extruders: development of technology analysis of flow. Adv Polym Technol. 1987;7:295–332. doi: 10.1002/adv.1987.060070306. [DOI] [Google Scholar]
- 9.Sprockel OL, Sen M, Shivanand P, Prapaitrakul W. A melt extrusion process for manufacturing matrix drug delivery systems. Int J Pharm. 1997;155:191–199. doi: 10.1016/S0378-5173(97)00165-8. [DOI] [Google Scholar]
- 10.Kawashima Y, Lin SY, Naito M, Takenama H. Direct agglomeration of sodium theophylline crystals produced by salting out in liquid. Chem Pharm Bull (Tokyo) 1982;30:1837–1843. [Google Scholar]
- 11.Sano A, Kuruki T, Handa T, Takeuchi H, Kawashima Y. Particle design of tolbutamide in the presence of soluble polymer or surfactant by the spherical crystallization technique: improvement of dissolution rate. J Pharm Sci. 1987;76:471–474. doi: 10.1002/jps.2600760612. [DOI] [PubMed] [Google Scholar]
- 12.Paradkar AR, Pawar AP, Chordiya JK, Patil VB, Ketkar AR. Spherical crystallization of celecoxib. Drug Dev Ind Pharm. 2002;28:1213–1220. doi: 10.1081/DDC-120015354. [DOI] [PubMed] [Google Scholar]
- 13.Pawar AP, Paradkar AR, Kadam SS, Mahadik KR. Crystallo-co-agglomeration: a novel process to obtain ibuprofen-paracetamol agglomerates. AAPS PharmSciTech. 2004;5(3):E44–E44. doi: 10.1208/pt050344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Lin K, Peck GE. Development of agglomerated talc. I. Evaluation of fluidized bed granulation parameters on the physical properties of agglomerated talc. Drug Dev Ind Pharm. 1995;21:159–173. doi: 10.3109/03639049509048101. [DOI] [Google Scholar]
- 15.Lin K, Peck GE. Development of agglomerated talc. II. Optimization of the processing parameters for the preparation of granulated talc. Drug Dev Ind Pharm. 1995;21:447–460. doi: 10.3109/03639049509026634. [DOI] [Google Scholar]
- 16.Bodmeier R, Chen H. Preparation and characterization of microspheres containing the anti-inflammatory agents, indomethacin, ibuprofen and ketoprofen. J Control Release. 1989;10:167–175. doi: 10.1016/0168-3659(89)90059-X. [DOI] [Google Scholar]
- 17.Kawashima Y, Niwa T, Takeuchi H, Hino T, Ito Y. Control of prolonged release and compression properties of ibuprofen microspheres with acrylic polymer, Eudragit RS, by changing their intraparticle porosity. Chem Pharm Bull. 1992;40:196–201. doi: 10.1248/cpb.40.196. [DOI] [PubMed] [Google Scholar]
- 18.Durig T, Fassihi R. Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experimental extended release formulation. J Pharm Sci. 1997;86:1092–1098. doi: 10.1021/js970052v. [DOI] [PubMed] [Google Scholar]
- 19.Kadam SS, Mahadik KR, Paradkar AR inventors. A process for making agglomerates for use as or in a drug delivery system. Indian Patent 183036. Feb. 14, 1997.
- 20.Kadam SS, Mahadik KR, Paradkar AR. inventors. A process for making agglomerates for use as or in a drug delivery system. Indian Patent 183481. Feb. 14, 1997.
- 21.Morishima K, Kawashima Y, Kawashima Y, Takeuchi H, Niwa T, Hino T. Micromeritic characteristics and agglomeration mechanisms in the spherical crystallization of bucillamine by the spherical agglomeration and the emulsion solvent diffusion methods. Powder Technol. 1993;76:57–64. doi: 10.1016/0032-5910(93)80041-8. [DOI] [Google Scholar]
- 22.Sethi PD. Quantitative Analysis of Drugs in Pharmaceutical Formulations. 2nd ed. Delhi, India: CBS Publication; 1993. Paracetamol, Ibuprofen. [Google Scholar]
- 23.United States Pharmacopeial Convention.United States Pharmacopoeia. Rockville, MD: United States Pharmacopeia; 1975.
- 24.Shirakura O, Yamada M, Hashimoto M, Ishimaru S, Takayama K, Nagai T. Particle size design using computer optimization technique. Drug Dev Ind Pharm. 1991;17:471–483. doi: 10.3109/03639049109044257. [DOI] [Google Scholar]
- 25.Jarosz PJ, Parrot EJ. Comparison of granule strength and tablet strength. J Pharm Sci. 1983;72:530–535. doi: 10.1002/jps.2600720513. [DOI] [PubMed] [Google Scholar]
- 26.Pawar PH, Pawar AP, Mahadik KR, Paradkar AR. Evaluation of tableting properties of agglomerates obtained by spherical crystallisation of trimethoprim. Indian J Pharm Sci. 1998;60:24–28. [Google Scholar]
- 27.Rubinstein MH, Musikabhumma P. A universal friability test for tablet granules. Pharm Acta Helv. 1978;53:125–129. [PubMed] [Google Scholar]
- 28.Leuenberger H. The compressibility and compactibility of powder systems. Int J Pharm. 1982;12:41–55. doi: 10.1016/0378-5173(82)90132-6. [DOI] [Google Scholar]
- 29.Sanghavi NM, Sivanand R, Kotwaney HN. Dissolution pattern of miniscular sulfisoxazole. Ind J Pharm Sci. 1979;41:116–117. [Google Scholar]
- 30.Alsaidan SM, Abdulhakeem AA, Eshra AG. Improved dissolution rate of indomethacin by adsorbents. Drug Dev Ind Pharm. 1998;24:389–394. doi: 10.3109/03639049809085635. [DOI] [PubMed] [Google Scholar]
- 31.Kawashima Y, Handa T, Tekeuchi H, Okumara M, Katou H, Nagata O. Crystal modification of phenytoin with polyethylene glycol for improving mechanical strength, dissolution rate and bioavailability by spherical crystallization technique. Chem Pharm Bull (Tokyo) 1986;34:3376–3383. doi: 10.1248/cpb.34.3376. [DOI] [PubMed] [Google Scholar]
- 32.Kawashima Y, Handa T, Takeuchi H, Okumura M. Effects of polyethylene glycol on size of agglomerated crystals of phenytoin prepared by the spherical crystallization technique. Chem Pharm Bull (Tokyo) 1986;34:3403–3407. doi: 10.1248/cpb.34.3403. [DOI] [PubMed] [Google Scholar]