RESUMEN
The overall stability of medicated chewing gums is investigated under different storage conditions. Active substances with different chemical stabilities in solid state are chosen as model drugs. The dosage form is a three layer tablet obtained by direct compression. The gum core contains the active ingredient while the external layers are formulated to prevent gum adhesion to the punches of the tableting machine. Two accelerated test conditions (40°C/75% RH and 30°C/65% RH) are performed for 6 months. Furthermore, a long-term stability test at room conditions is conducted to verify the predictability of the results obtained from the stress tests. Some drugs are stable in all the conditions tested, but other drugs, generally considered stable in solid dosage forms, have shown relevant stability problems particularly when stress test conditions are applied to this particular semi-solid dosage forms. For less stable drugs, the stress conditions of 40°C/75% RH are not always predictable of chewing gum stability at room temperature and may produce false negative; intermediate conditions, 30°C/65% RH, are more predictive for this purpose, the results of drug content found after 6 months at intermediate stress conditions and 12 months at room conditions are generally comparable. But the results obtained show that only long-term conditions stability tests gave consistent results. During aging, the semi solid nature of the gum base itself, may also influence the drug delivery rate during chewing and great attention should be given also to the dissolution stability.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Estabilidad de Medicamentos , Goma de Mascar , Almacenaje de Medicamentos , Calor/efectos adversos , Reproducibilidad de los Resultados , Solubilidad , Comprimidos , Factores de TiempoRESUMEN
This article proposes thermogravimetric analysis (TGA) as a useful method to investigate the hydration behaviour of hydrophilic matrix tablets containing hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) or a mixture of these two polymers and four drugs with different solubility. The hydration behaviour of matrix systems was studied as a function of the formulation composition and of the dissolution medium pH. TGA results suggest that the hydration of matrices containing HPMC is pH-independent and not affected by the characteristics of the loaded drug; this confirms HPMC as a good polymer to formulate controlled drug delivery systems. On the other hand, the performances of NaCMC matrix tablets are significantly affected by the medium pH and the hydration and swelling of this ionic polymer is influenced by the loaded drug. For systems containing the two polymers, HPMC plays a dominant role in the hydration/dissolution process at acidic pH, while at near neutral pH both the cellulose derivatives exert a significant influence on the hydration performance of systems. The results of this work show that TGA is able to give quantitative highlights on the hydration behaviour of polymeric materials; thus this technique could be a helpful tool to support conventional hydration/swelling/dissolution studies.
Asunto(s)
Carboximetilcelulosa de Sodio/química , Metilcelulosa/análogos & derivados , Preparaciones Farmacéuticas/química , Comprimidos/química , Termogravimetría/métodos , Concentración de Iones de Hidrógeno , Derivados de la Hipromelosa , Metilcelulosa/química , Solubilidad , Agua/químicaRESUMEN
The evaluation of the potential use of a dye as indicator of in vivo drug release from a medicated chewing gum is described. The device is a three-layer tablet obtained by direct compression consisting of a gum core and two external protective soluble layers to prevent gum adhesion to the punches of the tableting machine. The active ingredient and a colour are contained in the gum core. To evaluate the drug and the dye release from the formulations, a chew-out study was performed by a panel of volunteers. The results obtained suggest that the use of a dye could be useful to indicate the chewing time necessary to complete drug delivery from medicated chewing gums.