Anhydrous Dibasic Calcium Phosphate Research Articles

Formulation and Evaluation of Eszopiclone Film Coated Immediate Release Tablets by Direct Compression Method

Eszopiclone is a class of drug with hypnotic effect and mainly used in the treatment of Insomnia. The main objective of the present study was to develop a pharmaceutically equivalent, stable, cost effective and quality improved formulation of immediate release tablets of Eszopiclone using different concentration of disintegrants and diluents mainly MCC. Pre formulation studies were performed prior to formulation. The tablets were compressed using lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, anhydrous dibasic calcium phosphate, magnesium stearate and opadry blue (white for 2mg) was used for coating the tablets. The tablets were formulated by direct compression method. And prior to the formulation, the pre formulation parameters analysed are bulk density, tapped density, compressibility index, Hausner's ratio, angle of repose and post compression characteristics like thickness, hardness, friability, disintegration time, drug release and assay. The stability studies were carried out for the reproducible batch F010 (3mg), F009 (1mg) and F010 (2mg) for three months. The results of the present study showed that among all the formulations, F008 for 3mg, F009 for 1mg and F010 for 2mg was better in all terms of pre formulation and post compression parameters and showed comparably a good dissolution profile like that of the marketed product, LUNESTA ®.

To study physical compatibility between dibasic calcium phosphate and cohesive actives using powder rheometer and thermal methods

Aim: An attempt is made to provide better understanding of the compatibility aspect of excipients with different properties of active pharmaceutical ingredient (API) using various rheological, thermal and morphological studies conducted on binary mixtures of Dibasic Calcium Phosphate anhydrous (DCP-A) and Dibasic Calcium Phosphate dihydrate (DCP-D) forms with cohesive API’s (Acetaminophen and Aspirin).Method: Binary mixtures of DCP’s were prepared by addition of 0% w/w to 50% w/w of the API in each powder blend. Powder rheological analysis were conducted using FT4 powder rheometer, rotational shear cell and empirical approaches such as angle of repose (AOR), Hausner ratio (HR) and Carr’s index (CI). Thermal analysis was conducted using differential scanning calorimetry (DSC) and thermal effusivity. Morphological studies were conducted using Scanning Electron Microscopy (SEM) to determine the fundamental differences between powder materials.Result/Conclusions: Powder rheometer showed distinctive understanding in the flowability behavior of binary mixtures with addition of increasing proportion of API’s than empirical approaches. Thermal approaches revealed the potential interaction of water of crystallization DCP-D while such interaction was absent in DCP-A. Binary mixtures prepared using DCP-D were better flowable while blends containing DCP-A were better in stability (physical), compressibility and permeability. This study allows the scientist to understand the powder packing of different blends with their flowability and compressibility parameter and helps selection of appropriate form of hydrate for relevant API.

Quantitative on-line vs. off-line NIR analysis of fluidized bed drying with consideration of the spectral background

Quantitative dehydration studies of dibasic calcium phosphate anhydrous (DCPA) in a small-scale cold-model fluidized bed dryer with process air control were conducted. Near-infrared spectroscopy (NIRS) with partial least squares regression (PLSR) was used to predict DCPAs’ residual moisture content. Loss-on-drying (LOD) was employed as a reference method and confirmed the actual moisture content of DCPA. First, dynamic PLSR modeling was carried out, i.e., the NIR spectra were on-line recorded and predicted throughout the drying process. Secondly, PLSR off-line modeling was performed, i.e., samples were consecutively thief-probed from the processor, put into glass vials and analyzed off-line. Furthermore, two background spectra were collected prior to the in- and off-line measurements in an attempt to increase the method’s sensitivity, i.e., (i) dry DCPA that was fluidized at respective process air velocity (on-line) or inside a glass vial (off-line) and (ii) Spectralon® – a highly reflecting standard reference material made of fluoropolymer. Benefits and drawbacks of the in- and off-line approaches with different spectral backgrounds are discussed in detail. The results indicated that (i) the thief-probed sample amount from the processor and thus the sample weight and (ii) the downtime between thief-probing a sample and its actual analysis via NIRS and LOD can bias the moisture content predictions.

The impact of roller compaction and tablet compression on physicomechanical properties of pharmaceutical excipients

Material properties play a significant role in pharmaceutical processing. The impact of roller compaction (RC) and tablet compression on solid fraction (SF), tensile strength (TS) and flexural modulus (FM) of Avicel DG [co-processed excipient with 75% microcrystalline cellulose (MCC) and 25% anhydrous dibasic calcium phosphate (DCPA)], lactose and 1:1 Mixture of the two was studied. Materials were roller compacted at different force and roller type and compressed into tablets over a range of compression pressures (CP). SF, TS and FM were determined for ribbons and tablets. Roller force was a significant variable affecting SF while roller type was not. Both SF and TS of tablets increased with CP with Avicel DG exhibiting greater TS than that of 1:1 Mixture while tablets of lactose had the lowest TS. The TS of tablets decreased exponentially with tablet porosity. Ribbon of Avicel DG had higher TS and lower SF than lactose and greater reworkability. This is attributed to plastic deformation of MCC resulting in high degree of bonding and fragmentation of DCPA that fills the void spaces during tablet compression. The lack of significant increase in SF and low tablet TS for lactose upon compression is likely due to its brittle fragmentation and some elastic recovery as shown by the high FM.

Comparison of retention and prececal digestibility measurements in evaluating mineral phosphorus sources in broilers ,

The objectives of this study were to compare measurements of retention and prececal (pc) digestibility in evaluating mineral phosphorus (P) sources in 3- and 5-wk-old broilers. A corn-soybean meal-based basal diet was used (0.35% P on DM basis). Anhydrous monosodium phosphate (MSP(a)) or anhydrous dibasic calcium phosphate (DCP(a)) was supplemented to increment the P concentration by 0.08%, 0.16%, and 0.24%. Titanium dioxide was used as the indigestible marker. Two retention trials with excreta collection from d 16 to 20 and d 30 to 34 were conducted (n = 8 birds per diet). Another 8 pens of 10 birds from the same hatch were allocated to each diet on d 11 or 25 each to measure pc digestibility in both age periods. After 10 d of feeding, these birds were euthanized and the content of a defined section of the terminal ileum was obtained. Percentage P retention and pc digestibility for MSP(a) and DCP(a) were calculated by linear regression analysis. In 3-wk-old broilers, P retention for MSP(a) was 70% and significantly higher (P < 0.001) than for DCP(a) (29%). Values determined for pc digestibility at the same age were very similar (67% for MSP(a) and 30% for DCP(a); P < 0.001). In 5-wk-old broilers, P retention was 63% (MSP(a)) and 29% (DCP(a); P < 0.001) and pc digestibility was 54% (MSP(a)) and 25% (DCP(a); P = 0.002). We concluded that both retention and pc digestibility can be used for evaluating mineral P sources in broilers based on a regression approach. In 3-wk-old broilers, results obtained with both approaches were the same. In 5-wk-old broilers, the ranking of the 2 P sources was also the same for both approaches. Values did not differ significantly between the 2 age periods, but further studies on the relevance of broilers' age in P evaluation are suggested.

Matrix tablets: the effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests.

Different hydroxypropyl methylcellulose (HPMC)/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed aiming to evaluate the influence of both components ratio in the control release of a water-soluble drug (theophylline). In order to characterise the matrix tablets, swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralised water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid). The HPMC/ADCP ratio has turned out to be the determinant in the matrix behaviour: the HPMC characteristic swelling behaviour was modulated, in some cases, by the ADCP characteristic acidic dissolution. When the HPMC/ADCP ratio was ≥0.69, buoyancy, continuous swelling and low theophylline dissolution rate from the matrices (H1, H2 and H3) were observed in all dissolution media. Consequently, these formulations could be adequate as gastro-retentive drug delivery systems. Additionally, HPMC/ADCP ratio ≤0.11 (H5 and H6) induces a pH-dependent drug release which could be applied to design control drug release enteric formulations (with a suitable enteric coating). Finally, a HPMC/ADCP ratio between 0.11 and 0.69 (H4) yield a gastrointestinal controlled drug release, due to its time-dependent buoyancy (7h) and a total drug delivery in 17h in simulated colonic fluid.

Comparison and evaluation of bone measurements for the assessment of mineral phosphorus sources in broilers ,

The main objective of this study was to compare different bone measurements in response to supplements of mineral P sources. Comparisons were also made with P retention and digestibility responses determined in a companion study and with blood inorganic phosphate (P(i)) responses. A corn-soybean meal-based basal diet was used (0.35% total P on DM basis). Anhydrous monosodium phosphate (MSP(a)) or anhydrous dibasic calcium phosphate (DCP(a)) was supplemented to increment the P concentration by 0.08%, 0.16%, or 0.24%. Each of the 7 diets was fed for 10 d starting 11 d (period 1) or 25 d posthatch (period 2). Bone ash and P were determined, and density criteria were measured using quantitative computed tomography. Responses were evaluated and compared based on linear regression analysis. In general, responses to MSP(a) had a greater slope than DCP(a) for all criteria studied. In period 1, differences between the slopes were significant (P < 0.05) for almost all bone criteria. In period 2, the slopes significantly differed for the amounts of ash and P of all bones studied, for tibia, tarsometatarus, and foot ash percentage, for total and cortical density of tibiae, but not for the other criteria. For the different bones, the ratio of slopes for MSP(a) and DCP(a) was very similar based on the amount of ash in both periods. Foot ash proved to be as sensitive as tibia ash for evaluation of mineral P sources in both periods. Ninety-four percent of the variance of the corticalis content based on quantitative computed tomography measurements could be explained by the amount of tibia ash in period 1. Blood serum P(i) and BW gain were not suitable for P evaluation. We concluded that the ranking of mineral P sources based on bone criteria differed from the ranking that was based on P retention or prececal digestibility. This underlines the need for developing a standard protocol of determination of available P in poultry.

Preparation and Characterization of Highly Porous Direct Compression Carrier Particles with Improved Drug Loading During an Interactive Mixing Process

The aim of this study was to prepare highly porous carrier particles by emulsion solvent evaporation and compare the loading capacity of these beads with two traditional carriers, sugar beads, and microcrystalline cellulose granules during an interactive mixing process. The porous carrier particles were prepared by an emulsion solvent evaporation process using cellulose propionate as a binder, anhydrous dibasic calcium phosphate, and ion exchange resins as a fillers, and polyethylene glycol as a pore inducer. Micronized furosemide or griseofulvin powder was mixed with the same volume of each carrier in an interactive mixing process. The tableting properties, drug loading per unit volume of carrier, content uniformity of the mixtures, and dissolution of the drugs from the mixtures were measured. The results showed that highly porous microcapsules with desirable hardness equivalent to that of sugar beads and MCC granules were successfully prepared. On average the loading capacity of the new carrier was 310% that of sugar beads and 320% that of MCC granules during an interactive mixing process with very good content uniformity. The tableting properties of the microcapsules were equivalent to that of microcrystalline cellulose granules, and the dissolution of the drugs from interactive mixtures prepared with the new carrier was equivalent to that of drug suspensions. This showed that the prepared microcapsule carrier could be used to improve the loading capacity during an interactive mixing and to prepare tablets by direct compression.

Physical Characterization of Dibasic Calcium Phosphate Dihydrate and Anhydrate

The dehydration of different commercial brands of dibasic calcium phosphate dihydrate (DCPD; CaHPO4·2H2O) was examined over a range of temperatures and water vapor pressures. To determine the main factors affecting the physical stability of DCPD, the baseline characterization of DCPD and dibasic calcium phosphate anhydrate (DCPA; CaHPO4) was conducted by thermogravimetric analysis, differential scanning calorimetry and X-ray diffractometry. The surface area and the DCPA content (present as an impurity) depended on the commercial source of DCPD. The larger particles contained a higher concentration of DCPA and the anhydrate exhibited a concentration-dependent acceleratory effect on the dehydration of DCPD. Unlike DCPD, DCPA is physically stable and resisted hydration even when dispersed in water for over 7 months in the temperature range of 4–50°C. In dosage forms containing DCPD, there is a potential for phase transformation to DCPA, while the reverse transition, that is, DCPA→DCPD appears to be extremely unlikely. Thus, the risk of physical transformation can be minimized by using DCPA in formulations.

Formulation of controlled-release baclofen matrix tablets. II. Influence of some hydrophobic excipients on the release rate and in vitro evaluation.

The aim of this study was to investigate the influence of polymer level and type of some hydrophobic polymers, including hydrogenated castor oil (HCO); Eudragit RS100 (E-RS100); Eudragit L100 (E-L100), and some fillers namely mannitol [soluble filler], Dibasic calcium phosphate dihydrate (Emcompress) and anhydrous dibasic calcium phosphate [insoluble fillers] on the release rate and mechanism of baclofen from matrix tablets prepared by a hot-melt granulation process (wax tablets) and wet granulation process (E-RS100 and E-L100 tablets). Statistically significant differences were found among the drug release profile from different classes of polymeric matrices. Higher polymeric content (40%) in the matrix decreased the release rate of drug because of increased tortuosity and decreased porosity. At lower polymeric level (20%), the rate and extent of drug release was elevated. HCO was found to cause the strongest retardation of drug. On the other hand, replacement of Emcompress or anhydrous dibasic calcium phosphate for mannitol significantly retarded the release rate of baclofen, except for E-L100 (pH-dependent polymer). Emcompress surface alkalinity and in-situ increase in pH of the matrix microenvironment enhanced the dissolution and erosion of these matrix tablets. The release kinetics was found to be governed by the type and content of the excipients (polymer or filler). The prepared tablets showed no significant change in drug release rate when stored at ambient room conditions for 6 months.

THE EFFECT OF TABLET MAKING ON THE MIGRATION OF CYANOCOBALAMIN FROM GRANULES DURING DRYING

The migration of cyanocobalamin upon drying of its wet granules was studied through the formulation of different granules using different diluents (lactose monohydrate and anhydrous dibasic calcium phosphate), different binders in different. concentrations; polyvinyl pyrrolidone (PVP k25), hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and gelatin at different drying temperatures (50°C and 70°C). Also, different layers of the dried granulation bed were separately compressed into their respective tablets and evaluated. The in vitro drug release from different formulated tablets was performed. The results showed that, granules prepared with dibasic calcium phosphate showed relatively a higher migration for the drug than those prepared with lactose. Also, drug migration decreased with increasing the binder concentration and viscosity. Mottling was extensively observed for batches prepared with low viscous binder solutions, while, it is diminished on using a highly viscous binder solutions. The tablets prepared with 10 % w/w gelatin were found to be the least mottled ones. In addition, they showed least friability percentage, highest hardness value, highest disintegration time and lowest dissolution rate. However, those prepared with 0.5 % MC showed highest friability percentage, lowest hardness value, lowest disintegration time and high dissolution rate. Generally, increasing the binder concentration resulted in slowing both mottling and the in vitro drug release from tablets.

Insensitivity of Compaction Properties of Brittle Granules to Size Enlargement by Roller Compaction

Pharmaceutical granules prepared by roller compaction often exhibit significant loss of tabletability, that is, reduction in tensile strength, when compared to virgin powder. This may be attributed to granule size enlargement for highly plastic materials, for example, microcrystalline cellulose. The sensitivity of powder compaction properties on granule size variations impacts the robustness of the dry granulation process. We hypothesize that such sensitivity of compaction properties on granule size is minimum for brittle materials because extensive fracture of brittle granules during compaction minimizes differences in initial granule size. We tested the hypothesis using three common brittle excipients. Results show that the fine (44-106 microm), medium (106-250 microm), and coarse (250-500 microm) granules exhibit essentially identical tabletability below a certain critical compaction pressure, 100, 140, and 100 MPa for spray-dried lactose monohydrate, anhydrous dibasic calcium phosphate, and mannitol, respectively. Above respective critical pressure, tabletability lines diverge with smaller granules exhibiting slightly higher tablet tensile strength at identical compaction conditions. Overall, tabletability of brittle granules is insensitive to granule size enlargement. The results provide a scientific basis to the common practice of incorporating brittle filler to a typical tablet formulation processed by roller compaction granulation.

Investigations on the availability of inorganic phosphate from different sources with growing White Pekin ducks

Methodological aspects of determination of P availability in ducks were addressed in this study. Three balance experiments with quantitative excreta collection were performed with growing male White Pekin ducks that were 3 wk of age. When P from monobasic calcium phosphate (MCP) was added in graded levels below the requirement to a low-P basal diet, ducks responded nonlinearly in P accretion. With increases in dietary Ca:P ratio from 1.2:1 to 1.6:1 to 2.0:1, ymax in P accretion increased from 0.91 to 0.97 to 1.03 g/duck during the 5-d period of measurement, and marginal efficiency of utilization (δy/δx) of P from MCP increased from 75 to 85 to 91%. The overall utilization of plant P from the low-P basal diet was adversely affected by increasing dietary Ca:P ratio and decreased from 49 to 45 to 40%. Seven inorganic P sources were supplemented to a low-P basal diet to increase P content by 0.9 or 1.9 g/kg. Utilization of P from the sources was lower at 1.9 g/kg compared with at 0.9 g/kg, although supply was still below requirement, indicating that ducks fed 1.9 g/ kg were in the diminishing part of the response curve. Thus, only the values determined at the low level of supplementation were considered as a measure of availability. P availabilities were 100% for monosodium phosphate, 96% for anhydrous dibasic calcium phosphate, 92% for calcium sodium magnesium phosphate, 91% for monodibasic calcium phosphate, 86% for 2 batches of dihydrated dibasic calcium phosphate, and 77% for calcium sodium phosphate. It was concluded that availability studies aiming to characterize the capacity of an ingredient require standardization with regard to the level of P supply and the dietary Ca:P ratio. Similar to results from other species, the availability of inorganic feed phosphates for ducks is on an overall high level, but differences between P sources should be considered in diet formulation.

Formulation design of double-layer in the outer shell of dry-coated tablet to modulate lag time and time-controlled dissolution function: Studies on micronized ethylcellulose for dosage form design (VII)

The dry-coated tablet with optimal lag time was designed to simulate the dosing time of drug administration according to the physiological needs. Different compositions of ethylcellulose (EC) powder with a coarse particle (167.5 microm) and several fine particles (< 6 microm), respectively, were mixed to formulate the whole layer of the outer shell of dry-coated tablets. The formulations containing different weight ratios of coarse/fine particles of EC powders or 167.5 microm EC powder/excipient in the upper layer of the outer shell to influence the release behavior of sodium diclofenac from dry-coated tablet were also explored. The results indicate that sodium diclofenac released from all the dry-coated tablets exhibited an initial lag period, followed by a stage of rapid drug release. When the mixture of the coarse/fine particles of EC powders was incorporated into the whole layer, the lag time was almost the same. The outer shell broke into 2 halves to make a rapid drug release after the lag time, which belonged to the time-controlled disruption of release mechanism. When the lower layer in the outer shell was composed of 167.5 microm EC powder and the upper layer was formulated by mixing different weight ratios of 167.5 microm and 6 microm of EC powders, the drug release also exhibited a time-controlled disruption behavior. Its lag time might be freely modulated, depending on the amount of 6 microm EC powder added. Once different excipients were respectively incorporated into the upper layer of the outer shell, different release mechanisms were observed as follows: time-controlled explosion for Explotab, disruption for Avicel and spray-dried lactose, erosion for dibasic calcium phosphate anhydrate, and sigmoidal profile for hydroxypropyl methylcellulose.

Effects of lubricant mixing on compression properties of various kinds of direct compression excipients and physical properties of the tablets

The effects of lubricant [magnesium stearate MgSt] mixing time on the characteristics of tablet formulation were investigated by using two types of mixers (twin-shell and high-speed mixers). Three kinds of excipients for the direct compression — spray-dried lactose (SDL), microcrystalline cellulose (MCC) and dibasic calcium phosphate anhydrous (DCPA) — were mixed with a lubricant, MgSt, by using a twin-shell or high-speed mixer, respectively. The tablets were compressed from the mixed powders at 98 MPa. The compression parameters of the tablets, such as the tensile strength, compression energy, compression availability and elastic recovery ratio, were evaluated based on the compression profiles and the tablet hardness. The tablet hardness of MCC decreased with an increase in mixing time in the high-speed mixer and the related compression properties of MCC changed depending on the hardness, but those of DCPA did not. The order of the effect of mixing was MCC > SDL > DCPA and the high-speed mixer was more effective than the twin-shell mixer. We conclude that the compression properties of DCPA did not fluctuate by mixing with MgSt under any conditions compared with other excipients.

Properties of Fujicalin®, a New Modified Anhydrous Dibasic Calcium Phosphate for Direct Compression: Comparison with Dicalcium Phosphate Dihydrate

The novel, commercially available, free-flowing spherically granulated dicalcium phosphate anhydrous (SGDCPA) Fujicalin for direct tableting was compared with directly compressible dicalcium phosphate dihydrate (DCPD), the properties of which are well known. The two excipients were investigated and compared with regard to their physical and powder properties, compressibility, and compactibility. As a consequence of the spherical shape of its particles, SGDCPA shows the same good flowability and even better compactibility. In contrast to DCPD, SGDCPA shows significant uptake of moisture when exposed to relative humidities (RHs) exceeding 70%. For both excipients, the main deformation mechanism is fragmentation, with SGDCPA yielding significantly stronger tablets.

Effect of Diluents on Tablet Integrity and Controlled Drug Release

The objective of this study was to evaluate the effect of diluents and wax level on tablet integrity during heat treatment and dissolution for sustained-release formulations and the resultant effect on drug release. Dibasic calcium phosphate dihydrate (DCPD), microcrystalline cellulose (MCC), and lactose were evaluated for their effect on tablet integrity during drug dissolution and heat treatment in wax matrix formulations. A newly developed direct compression diluent, dibasic calcium phosphate anhydrous (DCPA), was also evaluated. Compritol® 888 ATO was used as the wax matrix material, with phenylpropanolamine hydrochloride (PPA) as a model drug. Tablets were made by direct compression and then subjected to heat treatment at 80°C for 30 min. The results showed that MCC, lactose, and DCPA could maintain tablets intact during heat treatment above the melting point of wax (70°C–75°C). However, DCPD tablets showed wax egress during the treatment. MCC tablets swelled and cracked during drug dissolution and resulted in quick release. DCPD and lactose tablets remained intact during dissolution and gave slower release than MCC tablets. DCPA tablets without heat treatment disintegrated very quickly and showed immediate release. In contrast, heat-treated DCPA tablets remained intact through the 24-hr dissolution test and only released about 80% PPA at 6 hr. In the investigation of wax level, DCPD was used as the diluent. The drug release rate decreased as the wax content increased from 15% to 81.25%. The dissolution data were best described by the Higuchi square-root-of-time model. Diluents showed various effects during heat treatment and drug dissolution. The integrity of the tablets was related to the drug release rate. Heat treatment retarded drug release if there was no wax egress.

The bio-availability of phosphorus from feed phosphates for broilers as influenced by bio-assay method, dietary Ca-level and feed form

The apparent retention of P from feed phosphates was investigated in two balance trials (experiments 1 and 3) using a nearly P-free basal diet and fed respectively as pellets and crumbles. Experiment 2 was a 3-factorial comparative bio-assay growth trial, involving 2688 male broiler chicks, in which a low-P mash diet (0.7 g/kg non-phytin P) was supplemented to P levels of 1.3, 1.9, 2.5, 3.1 and 3.7 g/kg from commercial monobasic calcium phosphate monohydrate (MCPh) Ca(H 2PO 4) 2 · H 2O, dihydrated dibasic calcium phosphate (DCPh) CaHP0 4 · 2H 2O and anhydrous dibasic calcium phosphate (DCPa) CaHP0 4. Asymptotic regression models were fitted to the response parameter toe ash-% to derive relative P bio-availability values for the feed phosphates. The effect of two Ca levels (9.1 vs. 10.5 g/kg in experiment 1 and 8.5 vs. 10 g/kg in experiment 2) on P utilization was also studied. The apparent P retention with the pelleted diet was on average 78.1, 74.2 and 63.6% respectively for MCPh, DCPh and DCPa and significantly different (LSD = 3.3%). The effect of Ca was not significant. With the crumbled diet the apparent P retention appeared to be distinctly higher, being 85.5 ± 1.9 and 82.3 ± 1.6 for MCPh and DCPh. The results suggest that apparent P retention is markedly influenced by diet form (hardness of the pellets) and that the results of the latter balance trial are more useful for the formulation of crumbled or mash diets. The relative bio-availability of P from MCPh, DCPh and DCPa, obtained in the comparative trial was respectively 100, 93 and 85. This ranking was comparable with the relative ranking based on the apparent P retention in the feed phosphates in the balance trials. The results from the three experiments suggest the use of relative P utilization values in diet formulation for broilers.

Changes in Volume and Compression Energy upon Compression of Calcium Silicate Tablets

The compression mechanism of calcium silicate (Florite®RE, FLR)was evaluated by determining the physicochemical properties such as compression energy, volume reduction percentage during the compression process, and elastic recovery of FLR tablets. The results obtained were compared with those of microcrystalline cellulose (MCC), anhydrous dibasic calcium phosphate (ADCP), cornstarch (CS), and lactose (LAC). FLR is found to have higher plasticity in the compression process and lower elastic recovery in a wide range of tablet hardnesses compared with the other 4 excipients. The results also indicate that a large part of compression energy was consumed for plastic deformation and fragmentation of particles. These characteristics are attributable to FLR's porous structure and are responsible for FLR tablets' high hardness, an important propen'y in tablet formulation. As a consequence, it was suggested that FLR would be a useful excipient for the formation of tablets in the pharmaceutical industry.

Explosive properties of a nitroderivative compound (ITF 296), in bulk and mixed with anhydrous dibasic calcium phosphate: Involving a formulation approach

The explosive and explodibility parameters of a new organic nitrate drug, ITF 296, have been studied. ITF 296 does not possess explosive properties, as determined by European Community standard testing methods (heat, impact and friction tests). The decomposition and auto-ignition temperature, determined by differential scanning calorimetry, are substantially higher than the working temperature which can be achieved with this compound. However, the explodibility properties of ITF 296, as determined by a hot-wire ignition method (Hartmann modified apparatus) and a heat oven auto-ignition method, place ITF 296 in Dust Hazard Class I. The addition of anhydrous dibasic calcium phosphate strongly attenuates the explodability properties of ITF 296 and, consequently, the need for expensive anti-explosion measures in the development and production environment.