Homogeneous Powder Mixtures

The preparation of solid oral dosage forms consists of two steps. The first step is the preparation of a homogeneous powder mixture, and the second step is the even distribution of the powder mixture over the dose units. Mixing of solids to obtain a homogeneous mixture is in principle the same process whether capsules, powders or tablets are prepared. However, the requirements regarding the filling of the dose units are different for the three types of preparation. 

Mass for oral powders is easy to prepare but time-consuming to divide. The solids are mixed together and subsequently the powder mixture is divided evenly over the powder papers. The same applies to cachets. The preparation of capsules is quick but somewhat more complex, because the powder mixture should have a fixed volume, which is determined beforehand. Next, the powder mixture has to be divided evenly over the capsule shells. The preparation of tablets is in this regard more complex. Tablets are made with a tableting machine (see Sect. 28.7.3 for some brands), which imposes extra requirements to the flowability of the powder mixture. To minimise flow and segregation problems, powder mixtures are often granulated before compression. 

Real challenges for the preparation of the powder mixture arise from the situation in which tablets or capsules are needed to get access to the active substance. In the first place the pharmacist has to consider the suitability for grinding or crushing of the tablets or capsules and then he has to develop a reliable method to produce the required dilution of 

Coated tablets, such as enteric-coated tablets, and modified-release tablets are better not split or pulverised, because their specific features may be lost. If it is absolutely necessary to break them then the pharmacist must know beforehand the implications on the stability of the medicine and on its therapeutic effect (see Sect. 4.9). A controlled-release tablet that has been split may overdose. Splitting may also expose the taste of the medicine, which had originally been masked in the coated tablet. Only standard, non-coated tablets shall readily be processed into a powder mixture. 

To obtain the required amount of active substance the equivalent amount of whole tablets are counted. It is preferable to use several tablets to level out content differences between tablets. In principle there are two ways take an exact, counted number of tablets to pulverise, or to use an excess of tablets in pulverising and then weighing the required quantity. If an exact number of tablets is used, the resulting mean content of active substance in the final product has to be validated. 

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Leibovitz, J., Process using supercritical conditions for producing highly accurate and homogeneous powder mixture useful in fabrication of high quality ceramic superconductors, U.S. 5,011,819 (April 30,1991). 

Preparation of homogeneous powder mixture is a difficult task if powders are nanosized because such powders have the expressed tendency to agglomerate. 

The theoretical basis of the quantitative analysis of powder mixtures was developed by Alexander and Klug [1,45]. When an x-ray beam passes through any homogenous substance, the fractional decrease in the intensity, I, is proportional to the distance traveled, b. This relationship is given by... 

Extraction of samples. Plant tissues were lyophilized after harvest and ground to a homogeneous powder in a Wiley mill (no. 20 mesh). Samples (0.500 g) of lyophilized whole leaf were extracted in 125 mL roundbottom flasks by steeping in 25 mL of chloroform for 30 min. The extract was filtered and the filtrate set aside. The extraction flask and filtered solids were rinsed with an additional 15 mL of fresh chloroform. The filtrate from the rinse was then combined with the original filtrate and the resulting solution was evaporated to dryness with a rotary evaporator. The dry solids were redissolved in a mixture of 20.0 mL methanol and 5.0 mL acetone using sonication to assist in dissolving of all solid material. 

Calcined MCM-41 was dehydrated at 120°C under 10 3 torr for three hours. Different amounts of the copper tellurolate cluster I were then mixed with dehydrated MCM-41. The mixture was mechanically stirred under nitrogen at atmospheric pressure until a yellow homogeneous powder was obtained. TGA, PXRD and IR studies were then carried out. 

Diazirine 43 (1.0 g, 4.99 mmol) was dissolved in pyridine (20 mL) and H20 (maximum amount that allows soln to stay homogenous). Powdered KMn04 (4 equiv) was added and the soln stirred at 50 °C. After 20 h, the mixture was diluted with H20 (150 mL), acidified with 0.5 M H2SQ4 to pH 2-3, and aq... 

A mixture of acidic alumina (9.3 g) and ammonium acetate (4.4 g) was ground in a mortar until a homogeneous powder was formed. A solution of 0.5 mmol of 1,2-dicarbonyl compound and 0.5 mmol of aldehyde in 2 mL of diethyl ether or... 

Assessing the homogeneity of powder mixtures by on-line electrical capacitance... 

Eleven and two-tenths grams (0.05 mol) of 1,3-diphenyl-1,3-propanedione is ground in a mortar with 5.84 g. (0.017 mol) of tris(2,4-pentanedionato)chromium(III) until a fine homogeneous powder is obtained. The mixture is transferred to an Erlenmeyer flask equipped with a gas inlet tube. The flask is heated slowly in an oil bath or with a heating mantle, in a hood, with a slow stream of nitrogen (about 0.5 1./minute) flowing over the mixture. The mixture melts at about 75° at about 150°, 2,4-pentanedione is... 

The mixing homogeneity of an interactive mixture is not better compared with a random one, but it leads to an interaction between a fine component and a coarse carrier and then to a higher stability of the system. Pharmaceutical powder mixtures are quite often between a random and an interactive mixture, and... 

Cartilier, L.H. Moes, A. Effect of flowing adjuvants on the homogeneity and the kinetics of mixing of low dosage cohesive powder mixtures. Drug Dev. Ind. Pharm. 1986, 12 (8, 9), 1203-1218. 

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