Abstract
This study investigated the basic physico-chemical property and binding functionality of commonly used commercial direct compression binders/fillers. The compressibility of these materials was also analyzed using compression parameters derived from the Heckel, Kawakita, and Cooper-Eaton equations. Five classes of excipients were evaluated, including microcrystalline cellulose (MCC), starch, lactose, dicalcium phosphate (DCP), and sugar. In general, the starch category exhibited the highest moisture content followed by MCC, DCP, lactose, and finally sugars; DCP displayed the highest density, followed by sugar, lactose, starch, and MCC; the material particle size is highly processing dependent. The data also demonstrated that MCC had moderate flowability, excellent compressibility, and extremely good compact hardness; with some exceptions, starch, lactose, and sugar generally exhibited moderate flowability, compressibility, and hardness; DCP had excellent flowability, but poor compressibility and hardness. This research additionally confirmed the binding mechanism that had been well documented: MCC performs as binder because of its plastic deformation under pressure; fragmentation is the predominant mechanism in the case of lactose and DCP; starch and sugar perform by both mechanism.
Keywords: direct compression, binder, tensile strength, Heckel analysis, Kawakita analysis, Cooper-Eaton analysis
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References
- 1.Bolhuis GK. Materials for direct compaction. In: Alderborn G, Nyström C, editors. Pharmaceutical Powder Compaction Technology. New York, NY: Marcel Dekker Inc; 1996. pp. 419–478. [Google Scholar]
- 2.Wade A, Weller PJ. Handbook of Pharmaceutical Excipients. 2nd ed. Washington, DC: American Pharmaceutical Association; 1994. [Google Scholar]
- 3.Rudnic EM, Kottke MK. Tablet dosage forms. In: Banker GS, Rhodes CT, editors. Modern Pharmaceutics. New York, NY: Marcel Dekker Inc; 1996. pp. 333–391. [Google Scholar]
- 5.Parrott EL. Compression. In: Lieberman HA, Lachman L, Schwartz JB, editors. Pharmaceutical Dosage Forms: Tablets. New York, NY: Marcel Dekker Inc; 1990. pp. 153–182. [Google Scholar]
- 6.Paronen P, Iilla J. Porosity-pressure functions. In: Alderborn G, Nyström C, editors. Pharmaceutical Powder Compaction Technology. New York, NY: Marcel Dekker Inc; 1996. pp. 55–75. [Google Scholar]
- 7.Habib Y, Ausburger L, Reier G, Wheatley T, Shangraw R. Dilution potential: a new perspective. Pharm Dev Technol. 1996;1(2):205–212. doi: 10.3109/10837459609029895. [DOI] [PubMed] [Google Scholar]
- 8.Fell JT, Newton JM. The tensile strength of lactose tablets. J Pharm Pharmacol. 1968;20(8):657–758. doi: 10.1111/j.2042-7158.1968.tb09832.x. [DOI] [PubMed] [Google Scholar]
- 9.Heckel RW. An analysis of powder compaction phenomena. Trans AIME. 1996;221:1001–1008. [Google Scholar]
- 10.Nicklasson F, Alderborn G. Analysis of the compression mechanics of pharmaceutical agglomerates of different porosity and composition using the Adams and Kawakita equations. Pharm Res. 2000;17(8):949–954. doi: 10.1023/A:1007575120817. [DOI] [PubMed] [Google Scholar]
- 11.Lavoie F, Cartilier L, Thibert R. New methods characterizing avalanche behavior to determine powder flow. Pharm Res. 2002;19(6):887–893. doi: 10.1023/A:1016125420577. [DOI] [PubMed] [Google Scholar]
- 12.Lee YSL, Poynter R, Podczeck F, Newton JM. Development of a dual approach to assess powder flow from avalanching behavior.AAPS Pharm SciTech. 2000;1(3): Article 21. [DOI] [PMC free article] [PubMed]
- 13.Tsai T, Wu JS, Ho HO, Sheu MT. Modification of physical characteristics of microcrystalline cellulose by codrying with β-cyclodextrins. J Pharm Sci. 1998;87(1):117–122. doi: 10.1021/js960486a. [DOI] [PubMed] [Google Scholar]
- 14.Taylor MK, Ginsburg J, Hickey AJ, Gheyas F. Composite method to quantify powder flow as a screening method in early tablet or capsule formulation development.AAPS PharmSciTech. 2000, 1(3): Article 18. [DOI] [PMC free article] [PubMed]
- 15.van der Voort Maarschalk K, Bolhuis GK. Improving properties of materials for direct compression. Pharm Technol Europe. 1998;10(9):30–35. [Google Scholar]
- 16.van der Voort Maarschalk K, Bolhuis GK. Improving properties of materials for direct compression. Pharm Technol Europe. 1998;10(10):28–36. [Google Scholar]
- 17.Cole ET, Rees JE, Hersey JA. Relations between compaction data for some crystalline pharmaceutical materials. Pharm Acta Helv. 1975;50(1–2):28–32. [PubMed] [Google Scholar]
- 18.Roberts RJ, Rowe RC. The young's modulus of pharmaceutical materials. Int J Pharm. 1987;37:15–18. doi: 10.1016/0378-5173(87)90004-4. [DOI] [Google Scholar]
- 19.Olsson H, Nyström C. Assessing tablet bond types from structural features that affect tablet tensile strength. Pharm Res. 2001;18(2):203–210. doi: 10.1023/A:1011036603006. [DOI] [PubMed] [Google Scholar]