Desenvolupament i caracterització de comprimits matricials hidròfils de captopril

[cat] L’objectiu de la tesi doctoral ha estat el desenvolupament i la caracterització de comprimits matricials hidròfils de captopril. Actualment no existeix una forma farmacèutica d’alliberació modificada de captopril en el mercat, ja que el captopril és inestable al pH bàsic intestinal. La inestabilitat en l’intestí, juntament amb l’elevada solubilitat en aigua que presenta, fa que el captopril sigui un principi actiu molt difícil de formular en sistemes d’alliberació modificada. Com a conseqüència de la recerca bibliogràfica realitzada, en aquesta tesi doctoral s’han elaborat uns sistemes matricials per compressió directa que es retinguin a l’estómac per tal d’assegurar una òptima estabilitat durant l’alliberació del captopril. La recerca del treball ha consistit en l’elaboració de formulacions amb diferents perfils de dissolució aplicant la metodologia Quality by Design (QbD), i la seva caracterització mitjançant el diagrama SeDeM i tècniques microscòpiques, les quals han estat utilitzades per primer cop en la caracterització de matrius hidròfiles. La metodologia utilitzada ha estat la combinació d’una recerca bibliogràfica molt exhaustiva, que juntament amb l´ús de tècniques microscòpiques avançades (Microscòpia de Força Atòmica, Microscòpia Electrònica de Rastreig, Angle de Contacte, i Microscòpia Confocal), s’han relacionat els paràmetres fisicoquímics de les matrius hidròfiles amb els paràmetres microscòpics. Els resultats de la recerca han estat l’obtenció d’unes metodologies que suposen un avenç científic en la caracterització de matrius hidròfiles. Els resultats obtinguts en aquesta tesi doctoral poden donar lloc a un ampli ventall d’estudis en el camp de la Tecnologia Farmacèutica, ja que els conceptes adquirits són potencialment aplicables en altres sistemes d’alliberació de fàrmac.[eng] The aim of the thesis has been the development and characterization of hydrophilic matrix tablets of captopril. Currently, there is no any modified release dosage form of captopril in the market, since captopril is unstable under basic intestinal pH conditions. The instability in the intestine, combined with a high water solubility, makes very difficult to formulate modified release systems of captopril. As the result of the bibliographic research carried out in this thesis, controlled release matrix tablets of captopril have been developed by direct compression with the aim to retain the dosage form in the stomach in order to ensure an optimal stability during the release of captopril. The research of this work has consisted in the preparation of formulations with different dissolution profiles applying the methodology Quality by Design (QbD) and their characterization using the SeDeM diagram, and microscopic techniques that have been used for the first time in the characterization of hydrophilic matrix tablets. The methodology used has been the combination of a very comprehensive bibliographic search and with the use of advanced microscopic techniques (Atomic Force Microscopy, Scanning Electron Microscopy, Contact angle, and Confocal Microscopy), it has been obtained a relationship between the physicochemical parameters of the hydrophilic matrices with the microscopic parameters. The results obtained in this thesis have been the obtaining of methodologies that represent a scientific breakthrough in the characterization of hydrophilic matrices. The results from this research can lead to a wide range of studies in the field of Pharmaceutical Technology, since the concepts acquired are potentially applicable to other drug delivery system

Formulation and characterization of mucoadhesive controlled release matrix tablets of captopril

The purpose of this study is to characterize controlled release matrix tablets of captopril and to find out the physicochemical properties that have an effect on the mucoadhesion process. The hydrophilic matrix tablets contain captopril, microcrystalline cellulose, barium sulfate, ascorbic acid, ethylcellulose N100, hydroxypropylmethylcellulose K15M, talc, magnesium stearate and colloidal silicon dioxide. The physicochemical properties of the formulations have been characterized using confocal microscopy, contact angle, and scanning electron microscopy. The potential mucoadhesion capabilities of the formulations were assessed measuring the surface free energy, the polar and dispersive forces, the spreading coefficients, the surface roughness, and the network structure of the hydrophilic matrix tablets. The results show that when the concentration of HPMC K15M increases, the spreading coefficients of polymer over mucus and mucus over polymer are more positive, thus increasing the contact between the matrix tablets with the mucus layer. The formulation that contains 15% of HPMC K15M is the formulation that presents a greater swelling capacity, a greater increase in surface roughness, and larger pores within the matrix. This formulation has a higher chain mobility and more free macromolecular chains able to diffuse in the mucus layer. Therefore, this formulation has the greatest potential mucoadhesion capability

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses