Using Amphiphilic Polymer Micelles as the Templates of Antisolvent Crystallization to Produce Drug Nanocrystals

Abstract

Biocompatible and biodegradable amphiphilic polymeric micelles (PLA-CMCS-g-OA) were prepared by surface grafting of oleic acid and polylactic acid onto carboxymethyl chitosan and were used as templates for the crystallization of camptothecin. The camptothecin (CPT) nanocrystals prepared by the novel micelle-templated antisolvent crystallization (mt-ASC) method demonstrated higher crystallinity, narrower particle size distribution, and slower release characteristic than those prepared by conventional antisolvent crystallization (c-ASC) using a high initial concentration and fast addition rate. In particular, the CPT release behavior of mt-ASC products in phosphate buffer solutions presented a pH-responsive characteristic with the increasing release rate of CPT under lower pH conditions. This work confirmed that amphiphilic nanomicelle-templated crystallization was an effective method for preparing drug nanocrystals.

Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate

“…After the reaction, analysis through 1 H-NMR of the reaction material was conducted, and results showed that the AA-CMCS conjugate was successfully prepared [ 26 ]. Amide bond formation between the carboxyl group of AA and the amine bond of CMCS was responsible for the formation of AA-CMCS conjugate.…”

“…The appearance of a characteristic ring of methine protons of AA-CMCS conjugate spectra in the region of 5.55–5.44 ppm proved the grafting of CMCS with AA in the AA-CMCS conjugate as shown in Figure S3 . Also, the broadening of peaks of (CH 2 )n and conjugated double bonds were observed at 1.7 ppm and 5.5 ppm in the spectra of the AA-CMS conjugate which was due to the presence overlap of the methylene proton adjacent to a double bond with the acetamide group protons [ 26 ].…”

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

“…In antisolvent crystallization, the antisolvent or precipitant provides the driving force of the supersaturation of the solute (drug) by decreasing its solubility [28][29][30][31][32][33][34]. Antisolvent crystallization has numerous advantages compared to the other crystallization methods, such as low cost, ease of scale-up, and superior control on the polymorph and size distribution of drug crystals, which can consequently lead to the enhancement of the final API solubility.…”