Comparative effects of some hydrophilic excipients on the rate of gabapentin and baclofen lactamization in lyophilized formulations
详细信息 查看全文
- 作者：Annalisa Cutrignelli ; Nunzio Denora ; Angela Lopedota ; Adriana Trapani ; Valentino Laquintana ; Andrea Latrofa ; Giuseppe Trapani ; Gaetano Liso
- 关键词：Gabapentin ; Baclofen ; Lactamization ; Stability ; Drug-excipients freeze-dried mixtures
- 刊名：International Journal of Pharmaceutics
- 出版年：2007
- 出版时间：6 March 2007
- 年：2007
- 卷：332
- 期：1-2
- 页码：98-106
- 全文大小：694 K
文摘
The aim of this study was to gain insights into the role played by some excipients on the stability of gabapentin 1 and baclofen 2 which can undergo degradation giving rise to the corresponding lactams 2-azaspiro[4.5]decan-3-one 3 and 4-(4-chlorophenyl)-2-pyrrolidone 4, respectively. A screening study was carried out on drug and drug-excipient freeze-dried mixtures at 50 °C and under three different humidity values by using a number of commonly available excipients. These include hydroxypropyl-β-(HP-β-CD), sulfobutyl-β-cyclodextrin (SBE-β-CD), lactose, raffinose, trehalose, PVP-K30 and mannitol. For most cases, it was found that the lactam formation can be satisfactory described by an apparent zero-order equation. Excipients shown to negatively impact gabapentin stability are HP-β-CD, SBE-β-CD, lactose and PVP K30 while only this last excipient had a significant effect on the degradation of baclofen. The results can be rationalized in terms of conformational factors favouring the intramolecular dehydration reaction. A positive effect of moisture on the lactamization process was observed under some circumstances. Water may provide a favourable environment for degradation. These findings, taken together, should be considered during the selection of excipients for a possible formulation of gabapentin and baclofen.