title: In vitro and in vivo evaluation of amorphous solid dispersions generated by different bench-scale processes, using griseofulvin as a model compound.
abstract: Drug polymer-based amorphous solid dispersions (ASD) are widely used in the pharmaceutical industry to improve bioavailability for poorly water-soluble compounds. Spray-drying is the most common process involved in the manufacturing of ASD material. However, spray-drying involves a high investment of material quantity and time. Lower investment manufacturing processes such as fast evaporation and freeze-drying (lyophilization) have been developed to manufacture ASD at the bench level. The general belief is that the overall performance of ASD material is thermodynamically driven and should be independent of the manufacturing process. However, no formal comparison has been made to assess the in vivo performance of material generated by different processes. This study compares the in vitro and in vivo properties of ASD material generated by fast evaporation, lyophilization, and spray-drying methods using griseofulvin as a model compound and hydroxypropyl methylcellulose acetate succinate as the polymer matrix. Our data suggest that despite minor differences in the formulation release properties and stability of the ASD materials, the overall exposure is comparable between the three manufacturing processes under the conditions examined. These results suggest that fast evaporation and lyophilization may be suitable to generate ASD material for oral evaluation. However, caution should be exercised since the general applicability of the present findings will need to be further evaluated.
authors: Global Research and Development, DMPK, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Chiang.pochang@gene.com
authors: Po-Chang
authors: PC
authors: Chiang
authors: Yong
authors: Y
authors: Cui
authors: Yingqing
authors: Y
authors: Ran
authors: Joe
authors: J
authors: Lubach
authors: Kang-Jye
authors: KJ
authors: Chou
authors: Linda
authors: L
authors: Bao
authors: Wei
authors: W
authors: Jia
authors: Hank
authors: H
authors: La
authors: Jonathan
authors: J
authors: Hau
authors: Amy
authors: A
authors: Sambrone
authors: Ann
authors: A
authors: Qin
authors: Yuzhong
authors: Y
authors: Deng
authors: Harvey
authors: H
authors: Wong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D006118:Griseofulvin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013818:Thermogravimetry
chemical_list: D006118:Griseofulvin; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose