The effect of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) on carbamazepine (CBZ) polymorphic transformation has been investigated by an attenuated total reflectance-infrared (ATR-IR) spectroscopy and chemoinformatics. CBZ anhydrate samples were each kneaded with 35.0 μL of pure water, aqueous solution of 0.005 w/v% HPC, or that of 0.005 w/v% HPMC. Each paste was put on a germanium glass of an ATR accessory and was covered with a sheet of Parafilm® at 20 ± 2°C. Measured IR spectra were analyzed by a multivariate curve resolutionalternating least squares (MCR-ALS) and a two-dimensional correlation spectroscopic analysis. Source vectors of MCR-ALS were assigned to CBZ anhydrate and dihydrate. Concentration data of MCR-ALS were evaluated for the kinetics of CBZ polymorphic transformation. The combination of ATR-IR spectroscopy and MCR-ALS is concluded to be useful for the elucidation of rapid polymorphic transformation in suspension. The transformation rate is delayed by HPC and HPMC.

We propose an approach for the simultaneous determination of multiple components in pharmaceutical mixed powder based on powder X-ray diffraction (PXRD) method coupled with chemometrics. Caffeine anhydrate, acetaminophen and lactose monohydrate were mixed at various ratios. The samples were analyzed by PXRD method in the ranges of 2θ 5.00-30.0 and 35.0-45.0 degrees. Obtained diffractograms were analyzed by conventional peak intensity method, multi curve resolution (MCR)-alternating least squares (ALS) method and partial least squares (PLS) method. Constructed PLS models can most accurately predict the concentrations among different methods used. Each regression vector of PLS correlates not only to the compound of interest but also to the coexisting compounds. The combination of PXRD and PLS methods is concluded to be powerful approach for analyzing multi components in pharmaceutical formulations.Key words powder X-ray diffraction; partial least square; pharmaceutical formulationThe polymorphs and pseudo-polymorphs (hydrates and solvates) of pharmaceuticals exhibit different physicochemical properties such as solubility, dissolution rate, stability and hygroscopicity. These properties strongly relate to the pharmaceutical properties in their dosage forms such as specific bioavailability, efficacy, stability and toxicity.1) Pharmaceutical regulations are, therefore, required for producing appropriate bulk drugs, the crystalline modifications of which (i.e., polymorphism) are well specified or precisely controlled. 2)Powder X-ray diffraction (PXRD) analysis is the most frequently used method for identifying crystalline modifications and for determining their contents in bulk powders.3) Any crystals have their own PXRD patterns. Pharmaceutical formulations are, in general, composed of multiple components including excipients. PXRD is, therefore, useful to identify crystalline compounds in the formulation and to determine their amounts in a non-contact and non-destructive fashion. 4,5) However, PXRD method has large relative errors, typically around ±5%. Such shortcoming of PXRD method is serious when two or more components having broad and overlapping X-ray diffraction peaks are contained in one formulation.Regulatory authorities such as the U.S. Food and Drug Administration and the International Conference on Harmonization have requested to use Process Analytical Technology (PAT) in order to reduce the production risk of inferior pharmaceuticals.6) Since the introduction of guidelines for PAT, online and real-time analysis have increasingly been accepted in pharmaceutical industry as a tool for monitoring and controlling manufacturing process. Non-contact methods, such as PXRD analysis, near infrared (NIR) spectroscopy and terahertz spectroscopy have been paid attention as important tools for PAT. 6) Chemoinformatics are employed by pre-formulation scientists for the quantitative and qualitative analyses of NIR because they can provide ideal means for extracting quantitative information from complex spectra of mult...

Dissolution kinetics of a bilayer direct compress tablet was evaluated by using degassing cyclic flow UV-visible (Vis) spectroscopy with chemometrics. The model bilayer nicotinamide (NA)-pyridoxine hydrochloride (PH) 100.0 mg tablets were prepared via the dual compress method. The fast diffusion layer of the bilayer tablet contained nicotinamide, microcrystal cellulose, beta-lactose, magnesium stearate, and croscarmellose sodium. The slow release layer contained pyridoxine hydrochloride and carnauba wax. The monolayer direct compress tablets were prepared as dual ingredient (API)s formulation tablets. The degassing cyclic flow UV-Vis spectroscopy dissolution test was carried out using the prepared tablets. The dissolution test conditions were as follows: time, 60 min; temperature, 37°C; paddle method, 50 rpm, and UV-Vis spectra measurement 1 time/min. The UV-Vis spectra of the flow solution were measured in the range of 240-380 nm. API concentration was predicted by partial least squares (PLS) regression models based on UV-Vis spectra. The dissolution kinetics of the bilayer and monolayer tablets were evaluated based on the UV-Vis spectra with the predicted API concentration profile. The degassing flow system could prevent air bubbles in the flow cell at 1800 min. Therefore, simultaneous determination of NA and PH concentration based on the PLS regression was suggested to have high accuracy. PLS regression has advantages over the conventional λ max absorbance method of simultaneous determination. We found that the kinetics of the separated bilayer tablet can be evaluated by the same kinetic analysis method used for the single layer model tablet.