Optimum heat treatment conditions for masking the bitterness of the clarithromycin wax matrix.
The effects of the contents of aminoalkyl methacrylate copolymer E (AMCE) in a wax matrix on the mechanism of polymorphic transformation of glyceryl monostearate (GM) were clarified by evaluating the enthalpy change defined as 1.51 (DeltaH(1)-DeltaH(2))/DeltaH(2), where DeltaH(1) and DeltaH(2) denote the enthalpies in the first and second thermal analyses, respectively. Using this value, K(1), the rate constant of transformation from alpha-form to beta'-form, and K(2), the rate constant of transformation from beta'-form to beta-form, could be obtained. As the ratio of AMCE increased, K(2) increased, but a minimum point existed for K(1). K(1) was always larger than K(2), but gradually approached K(2) as the ratio of AMCE increased. The optimum temperature for the transformation of GM was 50 degrees C, at which the enthalpy change was maximum. To prepare the wax matrix preparation of clarithromycin (CAM), we considered 40 degrees C the optimum treatment temperature for the transformation of GM in a CAM wax matrix compounded from CAM, GM and AMCE, since the matrices were mutually welded at above 45 degrees C during the spray congealing process. Although K(1) and K(2) were almost the same at 40 degrees C, the rate of transformation was accelerated by tumbling. By applying the tumbling that accelerated the transformation of GM in a CAM wax matrix, almost all of the alpha-form disappeared, and the release of CAM from the wax matrix diminished when the enthalpy change was more than 0.8.
Pharmaceutics Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd. Saitama, Japan. toshio.yajima@po.rd.taisho.co.jp
Toshio
T
Yajima
Shigeru
S
Itai
Hirofumi
H
Takeuchi
Yoshiaki
Y
Kawashima
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry; D017291:Clarithromycin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry; D003460:Crystallization; D004339:Drug Compounding; D005079:Excipients; D005989:Glycerides; D006358:Hot Temperature; D007700:Kinetics; D011208:Powders; D013649:Taste; D013816:Thermodynamics; D014885:Waxes; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D005079:Excipients; D005989:Glycerides; D011208:Powders; D014885:Waxes; C048159:glyceryl monostearate; D017291:Clarithromycin