Powder blending

Given that NIRS is a rapid, nondestructive technique and that most pharmaceutical blend constituents absorb in the NIR, it has been applied off-line to assess blend homogeneity. In the mid-1990s scientists at Pfizer utilized on-line NIRS to successfully characterize powder blending.  

The application of NIRS does not resolve all concerns associated with accurate blend uniformity determination. Key questions arise, such as (1) is the NIR beam sampling within a unit dose and (2) are an effective number of unit doses being sampled throughout a blend These questions are not limited to NIRS, but are applicable to any diffuse reflectance optical technique. 

NIR methods are not the only on-line applications for blend monitoring FT-Raman and laser induced fluorescence (LIF) have been utilized. Refer to Chapter 11 for a comprehensive review of LIF. As stated herein, NIRS is well established as an effective and advantageous means to deem blend homogeneity and blending end point, however there are circumstances in which NIR is insufficient. For example, LIF can be more suitable for blends with low drug load. Lai and Cooney illustrated in a lab-scale experiment that LIE yielded a limit of detection below 0.02% w/w for a given API.  

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During the preformulation stage, the chemical and physical properties of the dmg moiety are studied exhaustively to ensure stabdity, safety, bioavadabdity, and therapeutic efficacy. Tablets are produced directly by compression of powder blends or granulations, which include a small percentage of fine, particle-sized powders. 

Several specialized technologies have been perfected for cosmetic products. Among these, emulsification, stick technology, and powder blending are prominent. 

Powder Blending. Cosmetic powders serve two primary functions. One group, commonly called body powders or talcs, is appHed to the skin to provide lubricity and to absorb excessive moisture. The second group, commonly referred to as face powders, exists in both loose and compressed forms and is used to impart some color to the skin and to dull excessive oiliness. 

The ductility of GRT-polyethylene blends drastically decreases at ground rubber concentration in excess of 5%. The inclusion of hnely ground nitrile rubber from waste printing rollers into polyvinyl chloride (PVC) caused an increase in the impact properties of the thermoplastic matrix [76]. Addition of rubber powder that is physically modihed by ultrasonic treatment leads to PP-waste ethylene-propylene-diene monomer (EPDM) powder blends with improved morphology and mechanical properties [77]. 

Alternatives to compounding in the melt are solution mixing or powder blending of solid particles. Mixing with the aid of solvents can be performed at lower temperatures with minimal shear. However, difficulties in removal of the solvent results in plasticization of tJie polymer matrix and altered erosion/drug release performance in addition to residual solvent toxicity concerns. Powder blending at room temperature minimizes thermal/shear stresses, but achieving intimate mixtures is difficult. 

Interesting attempts have been made to formulate water-setting cements by blending solid acid phosphates with the zinc oxide powder. The cement is then prepared by mixing this powder blend with water. These attempts may be considered to have failed. 

A more successful approach was that of Higashi et al. (1969a,b 1972). They blended solid add phosphate salts with zinc oxide powder. One add salt used was a predpitated hydrate of ZnH2P04. The cement was formed by mixing this powder blend with water. Work progressed to the point where three commercial brands of these so-called hydrophosphate cements appeared on the market. None met the spedfication requirements... 

Magnesium (or magnesia) phosphate cements are based on the reaction between ignited magnesium oxide and acid phosphates, which are generally modified by the addition of ammonium and aluminium salts. The phosphates may be either in solution or blended in solid form with the magnesium oxide. In the latter form the cement is formed by mixing the powder blend with water. 

Abdelrazig, Sharp El-Jazairi (1988, 1989) prepared a series of mortars based on a powder blend of MgO and ADP with a quartz sand filler. They were hydrated by mixing with water. A mortar I (MgO ADP silica water = 17T 12-9 70-0 12-5), with a water/solid ratio of 1 8, formed a workable paste which set in 7 minutes with evolution of ammonia. The main hydration product, struvite, was formed in appreciable amounts within 5 minutes and continued to increase. Schertelite also appeared, but only in minor amounts, within the first 5 minutes and persisted only during the first hour of the reaction. Dittmarite appeared in minor amounts after 15 minutes, and persisted. 

GM Irwin, GJ Dodson, LJ Ravin. Encapsulation of clomacron phosphate I. Effect of fiowability of powder blends, lot-to-lot variability, and concentration of active ingredient on weight variation of capsules filled on an automatic capsule filling machine. J Pharm Sci 59 547-550, 1970. 

The moisture uptake models we have discussed have been concerned with pure components. The deliquescing material could be a drug substance or an excipient material. In pharmaceuticals, however, mixtures of materials are also important. One possible situation involves mixing nondeliquescing and deliquescing materials that are formed into a porous tablet or powder blend. The obvious question is, Do the models for pure components apply to porous heterogeneous materials For pure components we have assumed that the mass and heat limiting transport... 

A similar study has been conducted in which the interaction of d-amphetamine sulfate with spray-dried lactose was investigated [32], Upon storage at elevated temperatures, discoloration of the powder blends was noted, and the new absorption bands characterized. One maximum was noted at 340 nm, and this was attributed to the chemisorption of the amine onto the lactose particles. The other band appeared at 295 nm and was attributed to the new compound ([Pg.47]

Often the character of materials in a mixture undergoes solid-state rearrangements due to the pressures associated with compaction, which may or may not be polymorphic in nature. Consider the pre-compression powder blend, whose DSC thermogram is shown in Fig. 4.16, and which features the presence of four endothermic transitions. In the postcompression, ground tablet sample whose DSC thermogram is shown in Fig. 4.17, the endotherms having maxima at 86.5 and 106°C remain relatively constant (maxima at 85.3 and 104.2°C). On the other hand, the third endotherm in the pre-compression thermogram shows considerable attrition in the post-compression sample, and an additional endotherm (not previously observed in the pre-compression sample)... 

Fig. 4.16. DSC thermogram of a powder blend prior to its compression into a tablet.

Fig. 4.17. DSC thermogram of the ground tablet resulting from compression of the powder blend of Fig. 16.

Examples Caustic + water Intense mixing Concentrated acid + aqueous solution Carbon adsorption Examples Low-intensity powder blending Dilution with similar solvent Screening Drying... 

Chemical structure, concentration, size and distribution of the rubber phase as well as adhesion to the matrix determine processing and final properties, specifically the impact strength. In the case of a powder blend, like PVC/rubber-systems, the characteristic powder data have also to be taken into account. 

The morphology of the PVC/rubber-blends depends primarily on the maximum temperature reached during manufacturing and to a limited extend on the history of the sample (powder blending or graft polymerization). 

The differences in the age of API post-size reduction (milling and particularly micronization), can significantly impact on the processability of the resultant powder blend. Vippagunta et al. (2010) found that milling can... 

Hancock, B.C., Colvin, J.T., Mullarney, M.P., and Zinchuk, A.V., The relative densities of pharmaceutical powders, blends dry granulation, and immediate release tablets, Pharm. Technol., 4, 64, 2003. 

S.S. Sekulic, H.W. Ward, D.R. Brannegan, et al. On-line monitoring of powder blend homogeneity by near-infrared spectroscopy. Anal. Chem., 68, 509 - 513 (1996). 

PA. Hailey, P. Doherty, P. Tapsell, P.T. Oliver and PK. Aldridge, Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy, part 1. system development and control, J. Pharm. Biomed. Anal, 14, 551-559 (1996). 

R.C. Lyon, D.S. Lester, E.N. Lewis, E. Lee, L.X. Yu, E.H. Jefferson and A. S., Hussain, Near-infrared spectral imaging for quality assurance of pharmaceutical products analysis of tablets to assess powder blend homogeneity, AAPS Pharm. Sci. Tech., 3(3), 1-15 (2002). 

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