1. Development of a Hydrophobicity-Controlled Delivery System Containing Levodopa Methyl Ester Hydrochloride Loaded into a Mesoporous Silica
Tamás Kiss, Gábor Katona, László Mérai, László Janovák, Ágota Deák, Gábor Kozma, Zoltán Kónya, Rita Ambrus Pharmaceutics. 2021 Jul 7;13(7):1039. doi: 10.3390/pharmaceutics13071039.
Background: The drug release of antiparkinsonian drugs is an important issue during the formulation process because proper release kinetics can help to reduce the off periods of Parkinson's disease. A 2-factor, 3-level (32) full-factorial design was conducted to evaluate statistically the influence of the hydrophobicity of mesoporous silica on drug release. Methods: Hydrophobization was evaluated by different methods, such as contact angle measurement, infrared spectroscopy and charge titration. After loading the drug (levodopa methyl ester hydrochloride, melevodopa hydrochloride, LDME) into the mesopores, drug content, particle size, specific surface area and homogeneity of the products were also analyzed. The amorphous state of LDME was verified by X-ray diffractometry and differential scanning calorimetry. Results: Drug release was characterized by a model-independent method using the so-called initial release rate parameter, as detailed in the article. The adaptability of this method was verified; the model fitted closely to the actual release results according to the similarity factor, independently of the release kinetics. Conclusions: The API was successfully loaded into the silica, resulting in a reduced surface area. The release studies indicated that the release rate significantly decreased (p < 0.05) with increasing hydrophobicity. The products with controlled release can reduce the off period frequency.
2. An efficient enantioselective synthesis of ( S)-α-methyl-serine methyl ester hydrochloride via asymmetrically catalyzed amination
Qiong Xiao, Yi-Fan Tang, Ping Xie J Asian Nat Prod Res. 2020 Jan;22(1):61-68. doi: 10.1080/10286020.2019.1634058. Epub 2019 Jul 16.
We present the synthesis of enantiomerically pure (S)-α-methyl-serine methyl ester hydrochloride from 2-methyl-3-((4-(trifluoromethyl)benzyl)oxy)propanal and di-p-chlorobenzyl azodicarboxylate via asymmetrically catalyzed amination with naphthylalanine derivative catalyst. The application of the organocatalyst of D-3-(1-Naphthyl)-alanine is the key step in the synthesis and ensures the product is obtained with high levels of stereocontrol.
