Population Balance Model Development Verification and Validation of Cooling Crystallization of Carbamazepine
CRYSTAL GROWTH & DESIGN
Authors: Liu, Yiqing C.; Acevedo, David; Yang, Xiaochuan; Naimi, Sean; Wu, Wei-Lee; Pavurala, Naresh; Nagy, Zoltan K.; O'Connor, Thomas F.
Abstract
Using process modeling to understand process dynamics and potentially explore the design space of a crystallization process is difficult because of its complex nature with many factors at play, such as initial concentration, supersaturation, seeding strategy, and flow pattern. In this work, a systematic approach is applied to sequentially estimate the growth and nucleation rate of the cooling crystallization of carbamazepine at various conditions in batch operation. Different formulations of the kinetic expressions are tested as a model discrimination exercise to obtain the best fit with the most confidence form. Then, based on the risk, determined by the purpose of the obtained model, verification and validation activities are applied. The model is verified and validated to predict concentration and D50 for a specific seeding strategy for crystallization mechanisms, including both nucleation and growth, are highly dependent on the seed PSD. A brief discussion is also given on the transferring of the batch-developed model to continuous operations in response to the growing interest in continuous crystallization development. It is found that the model can be transferred to continuous operations where the supersaturation and solid concentration are similar to those tested during batch experimentation. Because of the complex and interactive effects of supersaturation and solid conditions on crystallization kinetics, it is reasonable to conclude that in order to infer transferable crystallization kinetics, batch experimental conditions must be wide and similar enough to cover the potential continuous operating space.
Chitosan-coated liposome-containing carbamazepine and coenzyme Q10: design, optimization and evaluation
JOURNAL OF LIPOSOME RESEARCH
Authors: Sagiroglu, Ali Asram
Abstract
Conventional formulations cannot sufficiently control seizures and influence on cognitive corruption and oxidative stress with chronic usage in patients with epilepsy. To defeat this issue, it was planned to develop polymeric liposome formulations that are using for their bioavailability and enhancer impact in oral epilepsy treatment. In this study, chitosan-coated liposomal formulations that encapsulate carbamazepine (CBZ) and coenzyme Q10 (CoQ10) were prepared and optimized by utilizing response surface methodology (RSM). Encapsulation efficiencies of CBZ and CoQ10, which were chosen as dependent variables for optimized chitosan-coated liposomal formulations were determined as 76.13%+/- 2.34% and 82.36%+/- 3.15%, respectively. Narrow size distribution was provided with an average size of 187.1 +/- 2.35 nm, while a spherical and uniform shape was approved with transmission electron microscopy analyses. Cumulative release of 78.23% for CBZ and 27.12% for CoQ10 was obtained after 24 hours of in-vitro release study in sink conditions. Physical stability analyses demonstrated that optimum liposomes were convenient for storage at 5 +/- 3 degrees C for at least 90 days. As a result, optimum chitosan-coated liposome containing CBZ and CoQ10 formulations could be suggested as a hopeful approach concerning their release, particle size, high encapsulation efficiency and stability for the treatment of epilepsy.