Isothermal crystallization of Imwitor 742 from supercooled liquid state.
OBJECTIVE
Crystallization behavior of Imwitor 742 was investigated for use as a liquid-filled capsule carrier.


METHODS
The crystallization behavior of Imwitor 742 was assessed using DSC, X-ray diffraction, and microscopy. The physical stability of Imwitor 742 under refrigerated and ambient conditions was estimated by isothermal crystallization studies using DSC. The effect of hard capsule shells and additives on crystallization kinetics was also examined.


RESULTS
When Imwitor 742 was cooled in the DSC measurement, the form alpha appeared at -20 degrees C. When this form was heated from -40 degrees C, melt-crystallization into the form beta + beta' was initiated at -30 degrees C, followed by successive melting. Isothermal crystallization studies at temperatures higher than -14 degrees C yielded the form beta + beta'. The crystallization behavior was explained in terms of the Avrami model fitting by assuming 2-dimensional crystal growth. Kinetic analysis suggested that the liquid state of Imwitor 742 was maintained for 46 h and 40 months at 5 and 25 degrees C, respectively, although the deviation in induction time was expected to be large at these temperatures. Addition of hard capsule shells promoted the crystallization behavior, while addition of drug or water prolonged the induction time.


CONCLUSIONS
The supercooled liquid state of Imwitor 742 was quite stable. However, additives to retard crystallization should be used, because the deviation in the induction time was very large. Hard capsule shells enhanced the crystallization of Imwitor 742, possibly by acting as nuclei for crystal growth.
Kawakami
Kohsaku
K
PreClinical Development, Banyu Tsukuba Research Institute, 3 Okubo, Tsukuba, Ibaraki, Japan. kawakami.kohsaku@nims.go.jp
D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004075:Diglycerides / Q000737:chemistry*; D004337:Drug Carriers; D005780:Gelatin / Q000737:chemistry; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D050178:Monoglycerides / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D044367:Phase Transition; D013678:Technology, Pharmaceutical; D013696:Temperature; D013816:Thermodynamics; D014280:Triglycerides / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D002214:Capsules; D004075:Diglycerides; D004337:Drug Carriers; D050178:Monoglycerides; D019999:Pharmaceutical Solutions; D014280:Triglycerides; D014867:Water; D065347:Hypromellose Derivatives; D005780:Gelatin; D008747:Methylcellulose