ABSTRACT
The dissolution behaviors of base excipients from sustained-release formulations have been investigated using various methodologies. However, the dissolution of polymers has not been fully evaluated because differences between formulations are still verified only by the release of active pharmaceutical ingredients (APIs). In our previous study, we proposed a quick and simultaneous analysis of dissolved APIs and water-soluble polymers by ultra HPLC using charged aerosol and photodiode array detectors. The purpose of this study was to verify whether the analysis system could be adapted to other water-soluble polymers. Dissolution tests were conducted using matrix model tablets prepared from three polymers and three APIs (propranolol, ranitidine, and cilostazol) with different solubilities. The dissolution profiles of the polymers and APIs were determined using the proposed analysis system and compared. The results clarified differences in the dissolution behaviors of the APIs and polymers. The polymers, especially hydroxypropyl cellulose, exhibited the dissolution properties characteristic of each model formulation. Propranolol and ranitidine showed the diffusion type, while cilostazol showed the erosion type release mechanism due to their different solubilities. The release of cilostazol was delayed in all models compared to the polymer, which may be due to the aggregation of cilostazol in the gel layer. This analytical method can be used to study the dissolution behavior (diffusion or erosion) of APIs from matrix tablets containing various polymers. This method will provide useful information on release control, which will make it easier and more efficient to design appropriate formulations and analyze the release mechanisms.
Subject(s)
Pharmaceutical Preparations/analysis , Polymers/analysis , Chromatography, High Pressure Liquid , Drug Compounding , Drug Liberation , Solubility , Water/chemistryABSTRACT
The objective of the study is to develop a quick and simultaneous analysis system for the dissolution of the active pharmaceutical ingredient (API) and the formulation excipient in samples from the dissolution test by UHPLC using the charged aerosol and PDA detectors. The combination of two columns for size-exclusion chromatography (SEC) and the equipment of the charged aerosol detector allowed the quick determination of various water-soluble polymers. Three model sustained-release tablets, each containing a different API of different water solubility (propranolol (soluble), ranitidine (very soluble), and cilostazol (practically insoluble)), were prepared from polyethylene oxide (PEO) matrix to verify the applicability and utility of the analysis system. The dissolution of propranolol was the same as that of PEO, indicating that the diffusion rate of propranolol was consistent with the erosion rate of the PEO and that the dissolution of PRO was based on diffusion. Ranitidine was released faster than PEO, suggesting that ranitidine was diffused through the gel layer of PEO early upon contact with the dissolution medium and before PEO gel erosion. Cilostazol was released slower as compared to PEO, indicating that cilostazol dissolution was based on the polymer's erosion. These results suggested that the analysis system developed in this study is a precise and valid tool to study the dissolution behavior of both APIs and excipients. Optimization of the SEC column for the appropriate separation of APIs and excipients makes the analysis system more efficient and convenient to study the drug release mechanisms and to design formulations.
