Calcium phosphate dihydrate

Christofferson, J. Christofferson, M.R. (1976) The kinetics of dissolution of calcium phosphate dihydrate in water. J. Crystal Growth 35 79-88... 

For methylcellulose, increased matrix material concentration did not affect the release profile (Table 4). The sustained action can be directly attributed to the formation of a hydration layer by this polymer. This hydration layer, however, did not resist attrition and remain intact. Consequently, attrition becomes more important than diffusion the hydrated layer dissolves away almost as rapidly as it is formed. On the contrary, the dibasic calcium phosphate dihydrate did not diffuse outward, but rather became entrapped within the matrix and effected an increase in release of drug because its presence necessarily decreased the polymer concentration. 

The stability of excipients is almost always taken for granted. Obviously, there is the potential for a phase change with certain lower melting excipients, e.g., semisolid materials, however, this is not a chemical phenomenon although it may enhance the potential for interaction by increasing the effective interface available at which the interaction can take place. However, some materials are not stable under conditions encountered in excipient compatibility screening or accelerated stability testing. A notable example is dibasic calcium phosphate dihydrate. At temperatures as low as 37°C, under certain conditions, the dihydrate can dehydrate to form the anhydrous material with the concomitant loss of water of crystallization (25), and at 25°C, it is a stable solid with a shelf life, when stored correctly, of more than two years. 

Excipients both typically contain water and are required to interact with it. The water associated with excipients can exist in various forms. Studies with different materials have shown that water can exist in association with excipients in at least four forms that may be termed free water, bound water, structural water, and water of crystallization. Water associated with a particular excipient may exist in more than one form (26). The type of water will govern how it is implicated in interactions between the excipient and the API or another excipient. The so-called free water is the form that is most frequently implicated in excipient interactions. Bound water is less easily available for interaction, and structural water is usually the least available one. Water of crystallization can be very tightly bound into the crystal structure however, there are some comparatively labile hydrates, e.g., dibasic calcium phosphate dihydrate (see above). If water of crystallization remains tightly bound within the crystal structure, it is unlikely to participate in an excipient interaction. However, any material that is in equilibrium with air above 0% RH will have some free moisture associated with it. In reality, below about 20% RH, the amount of moisture will probably be insufficient to cause problems. However, if sufficient moisture is present (e.g., at a higher RH), it can facilitate the interaction between components of the formulation. 

The dibasic calcium phosphate dihydrate example discussed above is probably an extreme example of the instability of an excipient relating to the release of water. But many excipients exist in a hydrated state, and heating them for the purposes of compatibility studies, or accelerated stability testing, can cause any free water, and sometimes other types of water, to be released, which can then influence any potential interaction, or even interact itself with the drug. 

Landin M, Rowe RC, York P. Structural changes during the dehydration of calcium phosphate dihydrate. Eur J Pharma Sci 1994 2 245-252. 

Microcrystalline cellulose Dibasic calcium phosphate dihydrate Magnesium stearate Sodium stearyl fumarate Stearic acid 175 175 5... 

The water of hydration is relatively easily lost from dibasic calcium phosphate dihydrate, and this may have consequences for the stability of products containing it.P "... 

Dibasic calcium phosphate dihydrate has been reported to be incompatible with a number of drugs and excipients and many of these incompatibilities are expected to occur with dibasic calcium phosphate, anhydrous see Calcium phosphate, dibasic dihydrate. 

Schlack H, Bauer-Brandl A, Schubert R, Becker D. Properties of Fujicalin, a new modified anhydrous dibasic calcium phosphate dihydrate. Drug Dev Ind Pharm 2001 27(9) 789-801. 

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

Dibasic calcium phosphate dihydrate is nonhygroscopic and stable at room temperature. However, under certain conditions of temperature and humidity, it can lose water of crystallization below 100°C. This has implications for certain types of packaging and aqueous film coating since the loss of water of crystallization appears to be initiated by high humidity and by implication high moisture vapor concentrations in the vicinity of the dibasic calcium phosphate dihydrate particles. ... 

Dibasic calcium phosphate dihydrate is also used in toothpaste and dentifrice formulations for its abrasive properties. 

Dibasic calcium phosphate dihydrate is a white, odorless, tasteless powder or crystalline solid. It occurs as monoclinic crystals. 

Dibasic calcium phosphate dihydrate is widely used in tablet formulations both as an excipient and as a source of calcium and phosphorus in nutritional supplements. It is one of the more widely used materials, particularly in the nutritional/ health food sectors. It is also used in pharmaceutical products because of its compaction properties, and the good flow properties of the coarse-grade material. The predominant deformation mechanism of dibasic calcium phosphate coarse-grade is brittle fracture and this reduces the strain-rate sensitivity of the material, thus allowing easier transition from the laboratory to production scale. However, dibasic calcium phosphate dihydrate is abrasive and a lubricant is required for tableting, for example about 1% w/w of... 

Excipient Dibasic calcium phosphate dihydrate, coarse grade Manufacturer JRS Pharma LP. 

Excipient Dibasic calcium phosphate dihydrate Manufacturer Rhodia. 

Moisture content dibasic calcium phosphate dihydrate contains two molecules of water of crystallization, which can be lost at temperatures well below 100°C. 

Dibasic calcium phosphate dihydrate is widely used in oral pharmaceutical products, food products, and toothpastes and is generally regarded as a nontoxic and nonirritant material. However, oral ingestion of large quantities may cause abdominal discomfort. 

Grades of dibasic calcium phosphate dihydrate available for direct compression include Calstar (FMG Biopolymer), Di-Cafos (Ghemische Fabrik Budenheim), DI-TAB (Rhodia), and Emcompress (JRS Pharma LP). 

Accelerated stability studies carried out at elevated temperatures on formulations containing significant proportions of dibasic calcium phosphate dihydrate can give erroneous results owing to irreversible dehydration of the dihydrate to the anhydrous form. Depending on the type of packaging and whether or not the tablet is coated, the phenomenon can be observed at temperatures as low as 40°G after 6 weeks of storage. As the amount of dibasic calcium phosphate dihydrate in the tablet is reduced, the effect is less easy to observe. 

Lausier JM, Chiang C-W, Zompa HA, Rhodes CT. Aging of tablets made with dibasic calcium phosphate dihydrate as matrix. J Pharm Sci 1977 66(11) 1636-1637. 

Free-flowing materials that do not disintegrate Dibasic calcium phosphate dihydrate Excellent flow properties. Very brittle material, and is best used in combination with microcrystalline cellulose or directly compressible starch. 

Calcium monohydrogen phosphate dihydrate Calcium phosphate, dibasic, dihydrate Dicalcium phosphate dihydrate Phosphoric xid, caicium salt (1 1), dihydrate. Dibasic calcium phosphate dihydrate USP/BP excipient tor production of pharmaceutical tablets by direct compression process. Penwest Pharmaceuticals Co. 

Diluent lactose microcrystalline cellulose (M.C.C.) corn starch calcium phosphate dihydrate mannitol (see experimental design, table 9.10) 91%... 

According to Lalande and Rene [1987], in an analysis of milk deposits the calcium deposit appears to be calcium phosphate dihydrates (CoHPO. lHfi), octocalcium phosphates CaJd PO g.5HJJ) and hydroxyopatite Ca (PO. Oil) which is the least soluble form [Sandu and Lund 1985]. 

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