A top-down spectroscopic approach for correlating coating thickness distributions with the dissolution profiles of enterically coated pellets.

Pharmaceutical dosage forms such as tablets and capsules are often coated with a functional polymer to modify the drug release. To obtain the drug release profiles, ensure quality control and predict in-vivo performance, dissolution studies are performed. However, dissolution tests are time-consuming, sample destructive and do not readily allow for at-line or in-line characterization. Rapid assessment of functional coatings is essential for products where a single capsule is comprised of hundreds of functionally-coated pellets and the collective drug release kinetics of the entire capsule depends on contributions from each pellet. Here, single Raman measurements were used to evaluate the coating thickness distributions of a dosage form comprised of small, functionally-coated pellets in capsules. First, the composition and physicochemical properties of pellets were characterized by multivariate analysis assisted Raman mapping of pellet cross-sections. Second, a method of collecting single Raman spectrum with spectral contributions from the coating and API layers was developed and optimized to estimate the thickness of coatings. The coating thicknesses obtained from single Raman measurements of pellets in each capsule revealed thickness distributions that correlated with the dissolution profiles (capsules with one distribution had single stage release and capsules with two distributions had a two-stage release). Finally, an unsupervised multivariate analysis method was demonstrated as a rapid and efficient way to correlate dissolution profiles of enterically coated pellets. In summary, this study presents a non-destructive and rapid characterization method for assessing coating thickness and has the potential to be applied in process analytical technologies to ensure coating uniformity and predict product dissolution rate performance.

Developing a biodegradable tricalcium silicate/glucono-delta-lactone/calcium sulfate dihydrate composite cement with high preliminary mechanical property for bone filling.

Bone cements with the feature of easily shaping could ideally match the defect site and prevent the ingrowth of fibrous tissue. In this manuscript, a biodegradable tricalcium silicate (C3S)/glucono-delta-lactone (GDL)/calcium sulfate dihydrate (CSD) organic-inorganic composite cement was fabricated with shorter setting time (less than 15 min) and high preliminary mechanical property (5.27 MPa in the first hour). Many methods were applied to study the physicochemical and biological properties of the cement in vitro. The weight loss in PBS can reach 58% after 12 weeks soaking indicating the better biodegradability. The excellent bioactivity in vitro was emerging after the cement was soaked in the simulated body fluid. The cell experiments showed that suitable concentration of the extract liquid of cement was conducive to the proliferation, differentiation and extracellular matrix calcification of the mouse bone marrow stromal cells. Briefly, the C3S/GDL/CSD composite cement would have the bright capacity for bone filling.

Effects of pullulan on the biomechanical and anti-collapse properties of dicalcium phosphate dihydrate bone cement.

In this work, a modified dicalcium phosphate dihydrate (DCPD) bone cement with unique biodegradable ability in a calcium phosphate cement system was prepared by the hydration reaction of monocalcium phosphate monohydrate and calcium oxide and integration with pullulan (Pul), a non-toxic, biocompatible, viscous, and water-soluble polysaccharide that has been successfully used to improve defects in DCPD bone cement, especially its rapid solidification, fragile mechanical properties, and easy collapse. The effect of different contents of Pul on the structure and properties of DCPD were also studied in detail. The modified cement was characterised by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet-visible absorption, X-ray photoelectron spectroscopy analysis, and rheological property measurements. The results indicated that Pul promoted the hydration formation of DCPD, and interface bonding occurred between Pul and DCPD. With increasing content of Pul, the setting time of the DCPD bone cement increased from 2.6 min to 42.3 min, the compressive strength increased from 0 MPa to 20.4 MPa, and the anti-collapse ability also improved owing to the strong interface bonding, implying that the DCPD bone cement improved by Pul has better potential for application in the field of non-loading bone regenerative medicine compared to unmodified DCPD bone cement.