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Crystal growth formation in melt extrudates.
Int J Pharm. 2007 Aug 16; 341(1-2):162-72.IJ

Abstract

The purpose of the study was to investigate the physical state of hot-melt extruded guaifenesin tablets containing either Acryl-EZE or Eudragit L100-55 and to study the physicochemical factors influencing crystal growth of guaifenesin on the surface of the extrudates. The powder mixtures containing Acryl-EZE were extruded on a single-screw Randcastle Microtruder at 20rpm and at temperatures of 90, 95, 110 degrees C (zones 1, 2, 3, respectively) and 115 degrees C (die), before being manually cut into tablets (250+/-5mg). Extrudates containing Eudragit L100-55, TEC and guaifenesin were extruded at temperatures ranging from 60 to 115 degrees C. Modulated differential calorimetry (DSC) was used to demonstrate the plasticizing effect of guaifenesin on Eudragit L100-55. Powder X-ray diffraction (PXRD) showed that while the drug powder is crystalline, extrudates containing up to 25% drug exhibited an amorphous diffraction profile. Extrudates containing higher drug concentrations showed an amorphous profile with some crystalline peaks corresponding to guaifenesin, indicating that the limit of solubility of drug in the matrix had been exceeded. Scanning electron microscopy was used to demonstrate that drug crystallization was a surface phenomenon and dependent on the drug concentration. In vitro dissolution testing showed no effect of surface crystallization of guaifenesin on drug release rates of extruded matrix tablets. The influence of hydrophilic polymeric additives including PVP K25, polycarbophil, PEG 3,350, poloxamer 188 or poly(ethylene oxide) as crystal growth inhibitors was investigated at a level of 10% based on the drug content. The extent of crystal growth was reduced for all additives. Complete drug release in pH 6.8 phosphate buffer was prolonged from 4h in extrudates containing Acryl-EZE and guaifenesin to 8h in extrudates containing Eudragit L100-55, TEC and guaifenesin. Drug release in extrudates containing Eudragit L100-55 and guaifenesin was not affected by the presence of hydrophilic additives present at 10% based on the drug content. In vitro drug release studies showed no significant change during storage for up to 6 months at 25 degrees C/60% relative humidity and 40 degrees C/75% relative humidity.

Authors+Show Affiliations

College of Pharmacy, The University of Texas, Austin, TX 78712, United States. cdietzsch@mail.utexas.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17524578

Citation

Bruce, Caroline, et al. "Crystal Growth Formation in Melt Extrudates." International Journal of Pharmaceutics, vol. 341, no. 1-2, 2007, pp. 162-72.
Bruce C, Fegely KA, Rajabi-Siahboomi AR, et al. Crystal growth formation in melt extrudates. Int J Pharm. 2007;341(1-2):162-72.
Bruce, C., Fegely, K. A., Rajabi-Siahboomi, A. R., & McGinity, J. W. (2007). Crystal growth formation in melt extrudates. International Journal of Pharmaceutics, 341(1-2), 162-72.
Bruce C, et al. Crystal Growth Formation in Melt Extrudates. Int J Pharm. 2007 Aug 16;341(1-2):162-72. PubMed PMID: 17524578.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crystal growth formation in melt extrudates. AU - Bruce,Caroline, AU - Fegely,Kurt A, AU - Rajabi-Siahboomi,Ali R, AU - McGinity,James W, Y1 - 2007/04/19/ PY - 2006/09/12/received PY - 2007/02/08/revised PY - 2007/04/05/accepted PY - 2007/5/26/pubmed PY - 2007/9/22/medline PY - 2007/5/26/entrez SP - 162 EP - 72 JF - International journal of pharmaceutics JO - Int J Pharm VL - 341 IS - 1-2 N2 - The purpose of the study was to investigate the physical state of hot-melt extruded guaifenesin tablets containing either Acryl-EZE or Eudragit L100-55 and to study the physicochemical factors influencing crystal growth of guaifenesin on the surface of the extrudates. The powder mixtures containing Acryl-EZE were extruded on a single-screw Randcastle Microtruder at 20rpm and at temperatures of 90, 95, 110 degrees C (zones 1, 2, 3, respectively) and 115 degrees C (die), before being manually cut into tablets (250+/-5mg). Extrudates containing Eudragit L100-55, TEC and guaifenesin were extruded at temperatures ranging from 60 to 115 degrees C. Modulated differential calorimetry (DSC) was used to demonstrate the plasticizing effect of guaifenesin on Eudragit L100-55. Powder X-ray diffraction (PXRD) showed that while the drug powder is crystalline, extrudates containing up to 25% drug exhibited an amorphous diffraction profile. Extrudates containing higher drug concentrations showed an amorphous profile with some crystalline peaks corresponding to guaifenesin, indicating that the limit of solubility of drug in the matrix had been exceeded. Scanning electron microscopy was used to demonstrate that drug crystallization was a surface phenomenon and dependent on the drug concentration. In vitro dissolution testing showed no effect of surface crystallization of guaifenesin on drug release rates of extruded matrix tablets. The influence of hydrophilic polymeric additives including PVP K25, polycarbophil, PEG 3,350, poloxamer 188 or poly(ethylene oxide) as crystal growth inhibitors was investigated at a level of 10% based on the drug content. The extent of crystal growth was reduced for all additives. Complete drug release in pH 6.8 phosphate buffer was prolonged from 4h in extrudates containing Acryl-EZE and guaifenesin to 8h in extrudates containing Eudragit L100-55, TEC and guaifenesin. Drug release in extrudates containing Eudragit L100-55 and guaifenesin was not affected by the presence of hydrophilic additives present at 10% based on the drug content. In vitro drug release studies showed no significant change during storage for up to 6 months at 25 degrees C/60% relative humidity and 40 degrees C/75% relative humidity. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/17524578/Crystal_growth_formation_in_melt_extrudates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(07)00320-1 DB - PRIME DP - Unbound Medicine ER -