Biomedical subjects

Wenjin Cao

Publications and source records attributed to Wenjin Cao.

4 recordsLinked to original sources

PubMed2006

Differentiation and quantitative determination of surface and hydrate water in lyophilized mannitol using NIR spectroscopy.

Mannitol hydrate is a metastable form produced during lyophilization. It is unstable, and therefore can undergo dehydration to release water to the surrounding environment at room temperature. The analysis of this form is challenging due to its thermodynamic instability. This study describes the development of a fast and non-invasive method to determine the mannitol hydrate and surface water content in a lyophilized product using near-infrared (NIR) spectroscopy. The mannitol hydrate was produced through lyophilization and characterized using XRPD, TGA, and NIR spectroscopy. Quantitative methods for hydrate and surface water were developed for NIR spectra with curve fitting and partial least square (PLS) regression models. The curve fitting method deconvoluted the NIR spectra into hydrate and surface water peaks and generated a calibration model by correlating pure spectra peak area to concentration. The standard error of prediction (SEP) for hydrate and surface water content were 0.65 and 0.40%, respectively. The PLS model developed for the same sample set was better than the curve fitting model; SEP = 0.50% for hydrate water and 0.22% for surface water, respectively. The methods can be used to monitor the formation and stability of mannitol hydrate in mannitol-containing formulations during the lyophilization process.

Data Interpretation, Statistical↗

PubMed2005

Effect of milling and compression on the solid-state Maillard reaction.

The effects of milling and compression on the solid-state Maillard reaction between metoclopramide hydrochloride and lactose were investigated. Anhydrous metoclopramide hydrochloride was milled for various times, and then mixed with amorphous lactose. The mixtures were stored at 105 degrees C and 0% RH. The reactivity of metoclopramide hydrochloride towards the Maillard reaction increased with milling time, as the result of increased surface area, formation of amorphous content, and creation of defects. Metoclopramide hydrochloride anhydrate and lactose were mixed and the mixtures were compressed into tablets under pressure varied from 70 to 350 MPa. Both tablets and mixtures were stored at 105 degrees C and 0% RH for 9 days. For all three types of lactose used, spray-dried anhydrous lactose, spray-dried lactose monohydrate, and amorphous lactose, tablets exhibited higher reaction rate toward the Maillard reaction than the powder mixtures. Tablets containing metoclopramide hydrochloride and amorphous lactose prepared at higher pressure showed higher reaction rates than those prepared at lower pressure. This is due to increased contact between reactants and an increased amount of water retained in the tablets.

Compressive Strength↗

PubMed2003

Modeling of transmitted X-ray intensity variation with sample thickness and solid fraction in glycine compacts.

The previous paper in this series introduced an X-ray diffraction quantitation method for the polymorphic content in tablets made of pure components. Before the method could be transferred, further studies were required to explain the commonly observed X-ray intensity variation in analyzing compacts. The literature typically attributes the variation to partial amorphization under compression and/or to preferred orientation, without much viable explanation or compelling evidence. In this study, changes in intensity in compacts analyzed in transmission geometry were found to be primarily a function of sample thickness and solid fraction. A theoretical model was developed to describe the X-ray powder diffraction (XRPD) intensity as a function of solid fraction, mass absorption coefficient, and thickness. The model was tested on two sets of glycine compacts: one with varying thickness at constant solid fraction, and the other with various solid fractions at a given thickness. The results show that the model predicts the XRPD intensity at any given sample thickness and solid fraction. With this model, the intensity variation of compacts made under different compression conditions can be normalized, making the method transferable to various tablet geometries and facilitating the analysis over expected ranges of formulation and process variation.

Glycine↗

PubMed2002

Quantitative determination of polymorphic composition in intact compacts by parallel-beam X-ray powder diffractometry.

This paper details the development of a method using parallel-beam X-ray powder diffractometry as a novel means of determining polymorphic composition in intact compacts. Two polymorphic systems, chlorpropamide and glycine, were selected. The polymorphic components were weighed, mixed, and compressed using a Carver press with 3/8-in. concave tooling. The compacts were then analyzed using parallel-beam X-ray powder diffractometry in transmission geometry. The data were processed using the profile-fitting module in the Shimadzu XRD-6000 software V 4.1 (for NT 4.0/98). The integrated intensity ratio of a selected peak for each crystal form was used for quantitation of each polymorph. Excellent linear correlation was observed for both polymorphic systems. The convex shape of the compact surface had no effect on the XRD patterns. Since parallel-beam X-ray diffractometry is not sensitive to the shape of the sample surface, it provides a simple method for quantifying polymorphs in intact compacts. Further work to extend this to formulated tablets is ongoing. The relatively larger variation in one of the peaks in the chlorpropamide study was found to be consistent with the computational analysis of the slip behavior of the stable polymorph. This method provides the first reported non-invasive X-ray diffraction pattern quantitation of crystal forms in intact compacts.

Chemistry, Pharmaceutical↗