ABSTRACT
El siguiente trabajo tiene como objetivos clasificar los ingredientes farmacéuticos activos (IFAs) de los sólidos orales de liberación inmediata del Cuadro Básico de Medicamentos de Cuba (CBM) que son producidos nacionalmente, según el Sistema de Clasificación Biofarmacéutica (SCB), y proponer aquellos que podrían demostrar su intercambiabilidad terapéutica a través de ensayos de disolución in vitro. Para ello se utilizó el listado de medicamentos del CBM de Cuba del 2019 y se realiza una clasificación biofarmacéutica provisional consenso, a partir de diferentes clasificaciones biofarmacéuticas publicadas y de una extensiva revisión de la literatura. Se identificó que aproximadamente el 48% de los IFAs del CBM presentan polimorfismo y que el 12,3% de las formas sólidas orales del CBM de Cuba tienen un estrecho margen terapéutico, por lo que no pueden ser bioexonerados mediante estudios de bioequivalencia in vitro basados en el SCB. Se constató que un 50,8% de los IFAs de formas sólidas orales de liberación inmediata del CBM de Cuba han sido clasificados según el SCB por la OMS. La aplicación conjunta de diversas metodologías de clasificación biofarmacéutica permitió clasificar provisionalmente todos los IFAs de las formas sólidas orales del CBM, demostrando que el 66,1% pertenece a las clases I, III y I/III del SCB, por lo que podrían ser bioexonerados de ensayos de bioequivalencia in vivo en humanos
The goals of the present work are to classify the active pharmaceutical ingredients (APIs) of the oral solids of immediate release of the Essential List of Medicines of Cuba (CBM) that are produced nationally, according to the Biopharmaceutical Classification System (BCS), and to propose those that could demonstrate their therapeutic interchangeability through in vitro dissolution tests. For this was used the Cuban CBM drug list of 2019, and a provisional consensus biopharmaceutical classification is proposed, based on different published biopharmaceutical classifications and an extensive review of the literature. It was identified that approximately 48% of the CBM IFAs present polymorphism and that 12.3% of the oral solid forms of CBM in Cuba have a narrow therapeutic margin, for which reason they cannot be bioexonerated through in vitro bioequivalence studies based on BCS. It was found that 50.8% of the oral solid forms of CBM in Cuba have been classified according to SCB by WHO. The joint application of diverse methodologies of biopharmaceutical classification allowed to provisionally classify all the IFAs of the oral solid forms of CBM, demonstrating that 66.1% belongs to classes I, III and I/III of the SCB, reason why they could be biowaivered from in vivo bioequivalence assays in humans
Subject(s)
Pharmaceutical Preparations/classification , Biopharmaceutics/standards , Therapeutic Equivalency , Drugs, Essential/classification , Pharmaceutical Preparations/chemistry , Drugs, Essential/chemistry , Drugs, Essential/standards , Reference Standards , Cuba , Drug Evaluation , Solubility , In Vitro TechniquesABSTRACT
Se desarrolló y validó un método enzimático para la cuantificación del contenido de alcoholen los IFAs de Inmunoglobulina y Albúmina. En ambos casos el procedimiento analíticoresultó lineal, exacto, preciso y específico para el control de calidad. Se demostró que elmétodo fue lineal en el rango de 6.0 a 19.0 mg de alcohol/g de proteína para la albúmina y de9.2 a 27.6 mg de alcohol/g de proteína para la inmunoglobulina, respectivamente. El métodosugerido se aplicó con éxito en la determinación del contenido de alcohol como impureza en lotes industriales(AU)
An enzymatic method for the quantification of alcohol content in immunoglobulin andalbumin was developed and validated. In both materials, the analytical procedure was linear,accurate, precise and specific. The method was linear in the range from 6.0 to 19.0 mg ofalcohol/g of protein to albumin and to immunoglobulin from 9.2 to 27.6 mg of alcohol/g ofprotein, respectively. The proposed method was applied successfully in industrial batches forthe determination of the alcohol content as impurity(AU)
Subject(s)
Clinical Enzyme Tests/methods , Alcohols/isolation & purification , Immunoglobulins/analysis , Albumins/analysis , Industry/standards , Quality ControlABSTRACT
The tackiness of aqueous chitosan film coatings and effects of anti-sticking agents on sticking tendency, were evaluated. A novel rapid method exploiting minimum fluidization velocity to determine tackiness was introduced and tested. The pressure difference over the miniaturized fluidized-bed was precisely recorded as a function of velocity of fluidization air. High molecular weight chitosan plasticized with glycerol was used as a film-forming agent. Magnesium stearate, titanium dioxide, colloidal silicon dioxide and glyceryl-1-monostearate (GMS) were studied as anti-sticking agents. Film coatings were performed in a miniaturized top-spray coater. The incorporation of anti-sticking agents led to a clear decrease in tackiness of the chitosan films, and magnesium stearate and GMS were shown the most effective. Film-coated pellets containing magnesium stearate and GMS as an anti-sticking agent were very easily fluidized (showing very low values of minimum fluidization velocity) and were thus classified as the best flowing and the least sticking samples. Both these additives were found anti-sticking agents of choice for aqueous chitosan film coatings. Determination of the experimental minimum fluidization velocity in a fluidized bed, is a useful and sensitive method of measuring the tackiness tendency of film-coated pellets.