A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices

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• 作者：G. Verstraete^a ; P. Mertens^a ; W. Grymonpr&eacute ; ^a ; P.J. Van Bockstal^b ; T. De Beer^b ; M.N. Boone^c ; L. Van Hoorebeke^c ; J.P. Remon^a ; C. Vervaet^a ; ^{Chris.Vervaet@Ugent.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hot melt extrusion ; Twin screw melt granulation ; Matrices ; High drug load ; Sustained release ; Thermoplastic polyurethanes ; Metformin hydrochloride
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：602-611
• 全文大小：1859 K

文摘

During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride.

Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24 h, release from the TPU-based TSMG tablets was too fast (complete release within about 6 h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively.