Compression effects, polymorphism

T Matsumoto, N Kaneniwa, S Hihuchi, M Otsuka. Effects of temperature and pressure during compression on polymorphic transformation and crushing strength of chlorpropamide tablets. J Pharm Pharmacol 43(2) 74-78, 1991. 

The physicochemical characteristics of the active ingredient in relation to the dosage form and the suitability for its intended purpose was discussed in several EPARs, particularly relating to the solubility characteristics and absorption from the gut. The compression characteristics were also mentioned in some EPARs. The possible effects of different polymorphs or evidence that only a single polymorph is used are addressed as appropriate. Different amorphous or crystalline forms are also discussed. Where affecting the dosage form, selection properties such as unpleasant taste or smell are mentioned. 

A very powerful method for the evaluation of solubility differences between polymorphs or solvates is that of intrinsic dissolution, which entails measurements of the rates of solution. One method for this work is to simply pour loose powder into a dissolution vessel, and to monitor the concentration of dissolved solute as a function of time. However, data obtained by this method are not readily interpretable unless they are corrected by factors relating to the surface area or particle size distribution of the powder. In the other approach, the material to be studied is filled into the cavity of a circular dissolution die, compressed until it exhibits the effective planar surface area of the circular disc, and then the dissolution rate is monitored off the surface of the rotating disc in the die [130],... 

Progress has also been made in the simulation of the structures of 4-coordinate SiOj polymorphs both by using force fields fitted to experiment or to ah initio calculations, and by modified electron-gas calculations including the effect of oxygen polarization. Catlow et al. (1985) and Sanders et al. (1984) have established that O-Si-0 angle-dependent terms in the energy are needed to give proper structures and compressibilities... 

We think first of two polymorphs with no chemical variability. If the materials showed no self-diffusion, the profile of radial compressive stress would have a step. But creeping materials do show self-diffusion (because if wafers can behave as in Figure 1.2b they can also behave as in Figure 1.2a). Hence, a real profile is a curve, with no step. The effect of the interface diminishes exponentially away from the interface, and the length scale over which it diminishes to 1/e of its maximum value is a multiple of the material s characteristic length Lq. 

As shown by Otsuka and Matsuda (1993), it is always worth checking the effect of compression on a powder if the compound is known to be polymorphic. Using the XRPD patterns of chlorpropamide forms A and C, they examined the effect of temperature and... 

The effect of compressional force on the polymorphic transition in piroxicam has been examined for phase-pure materials, where the needle-like a-phase was found to convert to the cubic P-phase during compression [47]. The phase transformation took place only at higher applied forces, such that formation of the a-phase could only be observed after compression to a tablet hardness of 9 kg/cm. Compression of the P-phase yielded no changes in its crystalline form. 

The effect of temperature on polymorphic transformations that take place during compression has been studied. Tableting temperature was found to exert a definite effect on the polymorphic transformation of chlorpropamide during compression, and on the physical properties of the produced tablets [49]. Compression stress, distance, and energy were measured using a noncontact displacement transducer mounted... 

A study of the effect of temperature on the polymorphic transformation and compression of chlorpropamide Forms A and C during tableting has been reported [50]. With the aid of apparatus similar to that previously described [49], these authors used multitableting at room temperature and single tableting at 0-45°C to effect compression. In the first method, the stable Form A or the metastable Form C was loaded into the die and the sample was compressed with a compression stress of 196 MPa. It was found that both forms were mutually transformed, and as evident in Fig. 8, an equilibrium ratio of Forms A and C was attained above roughly 200 J/g of compression energy. 

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