Abstract
Valsartan is an antihypertensive active pharmaceutical ingredient (API), it is used in the amorphous state in the commercial products. As amorphous materials are metastable, amorphous valsartan can crystallize to valsartan E, promoting changes in the dissolution and bioavailability of the drug. Tablets containing metastable forms of APIs need special conditions for transport and storage in order to avoid crystallization (from amorphous state) or polymorphic transitions (from less stable crystalline structures). A multivariate calibration model based on interval partial least squares (iPLS) regression allied to net analyte signal (NAS) algorithm was built to simultaneously quantify amorphous (VAL-AM) and crystalline (VAL-E) valsartan. Mixtures of VAL-AM and VAL-E were used to produce tablets in order to simulate the crystallization of VAL-AM in a range from 0 to 100% of conversion. The calibration set included 11 samples and 5 samples were used as the external validation set. The following parameters of merit (POM) were obtained for both polymorphs in order to evaluate the calibration model quality: root mean square error (RMSE) for cross validation (RMSECV), validation (RMSEV) and calibration (RMSEC), sensitivity (SEN), selectivity (SEL), analytical sensitivity (γ), inverse analytical sensitivity (γ-1), limit of detection (LOD) and limit of quantification (LOQ).
Highlights
Due to the higher stability and convenience, most of medicines are marketed in solid dosages forms.[1,2] An active pharmaceutical ingredient (API) can be classified as crystalline or amorphous.[2,3,4] Amorphous solids present some desirable characteristics such as higher solubility, better dissolution profile and compressibility when compared to their crystalline forms
VAL-AM has a higher tendence for adsorption when compared to VAL-E.6,24,25
The method presented in this paper was able to simultaneously quantify mixtures of VAL-AM and VAL-E in the presence of excipients using Raman spectroscopy allied to multivariate analysis
Summary
Due to the higher stability and convenience, most of medicines are marketed in solid dosages forms.[1,2] An active pharmaceutical ingredient (API) can be classified as crystalline (crystals, polymorphs, solvates, cocrystals, etc.) or amorphous (non-crystalline).[2,3,4] Amorphous solids present some desirable characteristics such as higher solubility, better dissolution profile and compressibility when compared to their crystalline forms. Amorphous solids tend to crystallize because crystals are thermodynamically more stable Such transition is a problem since it can affect the bioavailability promoting changes in the dissolution profile.[3,5]
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