Calcium phosphate granules

Becker, G. L-, Chen, C., Grcenwalt, J. W., Lehninger, A. L. Calcium phosphate granules in the hepatopancreas of the blue crab Caltinetes sapidus. J. Cell. Biol. 61, 316 (1974)... 

D. Le Nihouannen, L.L. Guehennec, T. RouiUon, P Pilet, M. Bilban, P Layrolle, G. Daculsi, Micro-architecture of calcium phosphate granules and fibrin glue composites for bone tissue engineering. Biomaterials 27 (13) (2006) 2716-2722. 

Klein CP, van der Lubbe HB, de Groot K. A plastic composite of alginate with calcium phosphate granulate as implant material an in vivo study. Biomaterials. 1987 Jul 8(4) 308-10. 

Figure 9 The effect of moisture content on the porosity of -12+16 mesh calcium phosphate granules processed for 10 min circles, pan granulated squares, massed and screened. (From Ref. 6.)...

Daculsi, G., et al., 2010. Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels. J. Mater. Sci. Mater. Med. 21 (3), 855-861. Available at http //www.ncbi.nhn.nih.gov/pubmed/19882306. 

Curran, J. M., Gallagher, J. A., Hunt, J. A. (2005). The inflammatory potential of bipha-sic calcium phosphate granules in osteoblasts/macrophage co-culture. Biomaterials 26, 5313-5320. 

Native starches are used as disintegrants, diluents, and wet binders. However, their poor flow and high lubricant sensitivity make them less favorable in direct compression. Different chemical, mechanical, and physical modifications of native starches have been used to improve both their direct compression and controlled-release properties (Sanghvi, 1993 van Aerde and Remon, 1988). Schinzinger and Schmidt (2005) used potato starch as an excipient and compared its granulating behavior with a-lactose-monohydrate and di-calcium phosphate anhydrous in a laboratory fluidized bed granulator using statistical methods. 

In summary, when tested, the grades of calcium phosphate dibasic discussed above exhibited mechanical properties that were very appropriate for tablet compaction and thus for formulation processing by direct compression, dry granulation, or wet granulation. With this in mind, it is easy to understand the popularity of DCP in pharmaceutical tablet formulations. 

The insoluble Ca(II) salts of weak acids, such as calcium phosphate, carbonate, and oxalate, serve as the hard structural material in bone, dentine, enamel, shells, etc. About 99% of the calcium found in the human body appears in mineral form in the bones and teeth. Calcium accounts for approximately 2% of body weight (18,19). The mineral in bones and teeth is mosdy hydroxyapatite [1306-06-5] having unit cell composition Ca10(PO4)6(OH)2. The mineralization process in bone follows prior protein matrix formation. A calcium pumping mechanism raises the concentrations of Ca(II) and phosphate within bone cells to the level of supersaturation. Granules of amorphous calcium phosphate precipitate and are released to the outside of the bone cell. There the amorphous calcium phosphate, which may make up as much as 30—40% of the mineral in adult bone, is recrystallized to crystallites of hydroxyapatite preferentially at bone collagen sites. These small crystallites do not exceed 10 nm in diameter (20). 

Figure 18-1 Thin section of mitochondria of a cultured kidney cell from a chicken embryo. The small, dark, dense granules within the mitochondria are probably calcium phosphate. Courtesy of Judie Walton.

In addition to bacterialike mitochondrial ribosomes and small circular molecules of DNA, mitochondria may contain variable numbers of dense granules of calcium phosphate, either Ca3(P04)2 or hydroxylapa-tite (Fig. 8-34),4/18 as well as of phospholipoprotein.4... 

Diluents. In general, diluents make up most of the dosage form. The selection of diluents is very important, especially for low-dose formulations, since they may make up 85-95% of the granulation. These diluents may be soluble or insoluble. The most commonly used soluble fillers include lactose, mannitol and sucrose. Commonly used insoluble fillers include microcrystalline cellulose, starch, calcium sulfate, and dibasic calcium phosphate. 

Calcium Phosphate, Monobasic, occurs as white crystals or granules or as a granular powder. It is anhydrous or contains one molecule of water of hydration, but because of its deliquescent nature, more than the calculated amount of water may be present. It is sparingly soluble in water and is insoluble in alcohol. 

Diluents, although commonly presumed inert, do have the ability to influence the stability or bioavailability of the dosage form. For example, dibasic calcium phosphate (both anhydrous and dihydrate forms) is the most common inorganic salt used as a filler-binder for direct compression. It is particularly useful in vitamin products as a source of both calcium and phosphorous. Milled material is typically used in wet-granulated or roller-compacted formulations. The coarse-grade material is typically used in direct compression formulations. It is insoluble in water, but its surface is alkaline and it is therefore incompatible with drugs sensitive to alkaline pFI. Additionally, it may interfere with the absorption of tetracyclines [7]. 

Manufacturing (Wet Granulation) A mixture of a-methyldopa with lactose or calcium phosphate (for formulations FI or F2, respectively) is granulated with isopropanol solution of Kollidon 30 and passed through a sieve, the dry granules are mixed with Kollidon CL and magnesium stearate, and pressed with medium compression force. 

Calcium phosphate, dibasic offers high hardness and faster dissolution profile than lactose for a-methyldopa tablets in wet granulation. 

Probably the second most commonly used diluent in the wet granulation process is dibasic calcium phosphate. This substance is virtually insoluble in water and hence is always used in conjunction with a disintegrating agent. Its properties have been reviewed by Carstensen and Ertell. ... 

Two particle-size grades of anhydrous dibasic calcium phosphate are used in the pharmaceutical industry. Milled material is typically used in wet-granulated or roller-compacted formulations. The unmilled or coarse-grade material is typically used in direct-compression formulations. 

Takami K, Machimura H, Takado K, Inagaki M, Kawashima Y. Novel preparation of free-flowing spherically granulated dibasic calcium phosphate anhydrous for direct tabletting. Chem Pharm Bull 1996 44(4) 868-870. 

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