Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the Quality by Design method

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• 作者：A. Ková ; cs ; ^{anita.kovacs@pharm.u-szeged.hu} ; Sz. Berkó ; ^{berko@pharm.u-szeged.hu} ; E. Csá ; nyi ^{csanyi@pharm.u-szeged.hu} ; I. Csó ; ka ^{csoka@pharm.u-szeged.hu}
• 关键词：API ; active pharmaceutical ingredient ; CMAs ; critical material attributes ; CCS ; critical control strategy ; CPPs ; critical process parameters ; CQAs ; critical quality attributes ; DoE ; design of experiments ; DS ; design space ; ICH ; International Council for Harmonisation ; LD ; laser diffraction ; MP-SA ; micro-sized lipid particle containing salicyclic acid ; NLC SA ; nanostructured lipid carriers containing salicyclic acid ; NSAID ; non-steroidal anti-inflammatory drug ; PAT ; process analytical technology
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：99
• 期：Complete
• 页码：246-257
• 全文大小：2419 K
• 卷排序：99

文摘

The aim of our present work was to evaluate the applicability of the Quality by Design (QbD) methodology in the development and optimalization of nanostructured lipid carriers containing salicyclic acid (NLC SA). Within the Quality by Design methology, special emphasis is layed on the adaptation of the initial risk assessment step in order to properly identify the critical material attributes and critical process parameters in formulation development.NLC SA products were formulated by the ultrasonication method using Compritol 888 ATO as solid lipid, Miglyol 812 as liquid lipid and Cremophor RH 60® as surfactant. LeanQbD Software and StatSoft. Inc. Statistica for Windows 11 were employed to indentify the risks.Three highly critical quality attributes (CQAs) for NLC SA were identified, namely particle size, particle size distribution and aggregation. Five attributes of medium influence were identified, including dissolution rate, dissolution efficiency, pH, lipid solubility of the active pharmaceutical ingredient (API) and entrapment efficiency.Three critical material attributes (CMA) and critical process parameters (CPP) were identified: surfactant concentration, solid lipid/liquid lipid ratio and ultrasonication time. The CMAs and CPPs are considered as independent variables and the CQAs are defined as dependent variables. The 23 factorial design was used to evaluate the role of the independent and dependent variables. Based on our experiments, an optimal formulation can be obtained when the surfactant concentration is set to 5%, the solid lipid/liquid lipid ratio is 7:3 and ultrasonication time is 20 min. The optimal NLC SA showed narrow size distribution (0.857 ± 0.014) with a mean particle size of 114 ± 2.64 nm. The NLC SA product showed a significantly higher in vitro drug release compared to the micro-particle reference preparation containing salicylic acid (MP SA).