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The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry's screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.
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SUMMARY The purpose of this study was to evaluate physicochemical properties and dissolution studies of furosemide (FUR), hydrochlorothiazide (HCTZ) and nifedipine (NIF), low water solubility drugs, in raw materials and pharmaceutical formulations. Surface and physicochemical characterization techniques -scanning electronic microscopy (SEM), thermogravimetry (TG), X-ray diffraction (XRD) and infrared (IR) spectrometry- as well as physical and physicochemical tests on tablets and capsules were applied as supporting information on drug quality control. Simple, rapid, and efficient UV-Vis methods were developed and validated for the determination of FUR, HCTZ and NIF samples. SEM exhibited considerable differences in the crystal morphological structures. Among the drugs studied, except for furosemide, more than one polymorph was present in the samples. Drug release profiles were satisfactory for all products. FUR and HCTZ tablets exhibited similar dissolution profiles, with very rapid release to the pharmaceutical specialties (reference, similar and generic). For HCTZ tablets, the similar drug (f2= 48.74) is not equivalent to the reference drug. NIF capsules (reference and compounded) showed a release >80% of stated on product labels, in 10 minutes. The results obtained in this study suggest that the quality parameters and drug dissolution profiles may have been influenced by the morphology and size of the crystals, excipients, and technological processes.
RESUMEN El propósito de este estudio fue evaluar las propiedades fisicoquímicas y los estudios de disolución de furosemida (FUR), hidroclorotiazida (HCTZ) y nifedipina (NIF), medicamentos de baja solubilidad en agua, en materias primas y formulaciones farmacéuticas. Técnicas de caracterización fisicoquímica y de superficie: microscopía electrónica de barrido (SEM), termogravimetría (TG), difracción de rayos X (XRD) y espectrometría infrarroja (IR), así como pruebas físicas y fisicoquímicas en tabletas y cápsulas que se aplicaron como información de apoyo sobre el control de calidad. Se desarrollaron y validaron métodos simples, rápidos y eficientes de UV-Vis para la determinación de muestras de FUR, HCTZ y NIF. SEM exhibió diferencias considerables en las estructuras morfológicas de cristal. Entre las drogas estudiadas, a excepción de la furosemida, más de un polimorfo estaba presente en las muestras. Los perfiles de liberación de fármacos fueron satisfactorios para todos los productos. Las tabletas FUR y HCTZ exhibieron perfiles de disolución similares, con una liberación muy rápida a las especialidades farmacéuticas (referencia, similares y genéricas). Para las tabletas de HCTZ, el medicamento similar (f2= 48,74) no es equivalente al medicamento de referencia. Las cápsulas NIF (de referencia y compuestas) mostraron una liberación >80% de la indicada en las etiquetas del producto, en 10 minutos. Los resultados obtenidos en este estudio sugieren que los parámetros de calidad y los perfiles de disolución del fármaco pueden haber sido influenciados por la morfología y el tamaño de los cristales, excipientes y procesos tecnológicos.
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INTRODUCTION: Natural compounds are emerging as effective agents for the treatment of malignant diseases. Curcumin (diferuloylmethane), the active constituent of turmeric extract, has gained significant interest as a plant-based compound with anti-cancer properties. Curcumin is physiologically very well tolerated, with negligible systemic toxicity observed even after high oral doses administration. Despite curcumin's superior properties as an anti-cancer agent its applications are limited due to its low solubility and physico-chemical stability, rapid systemic clearance and low cellular uptake. AREAS COVERED: This review focuses on the development of curcumin nano-particle formulation to improve its therapeutic index through enhanced cellular uptake, localization to targeted areas and improved bioavailability. The feasibility of nano-formulation in delivering curcumin and the limitations and challenges in designing and administrating the nano-sized curcumin particles are also covered in this review. EXPERT OPINION: Nanotechnology is a promising tool to enhance efficacy and delivery of drugs. In this context, formulation of curcumin as nano-sized particles could reduce the required therapeutic dosages and subsequently reduced its cell toxicity. These nanoparticles are capable to provide local delivery of curcumin targeted to specific areas and thereby preventing systemic clearance. In addition, using specific coating, better pharmacokinetic and internalization of nano-curcumin could be achieved. However, the potential toxicity of nano-carriers for curcumin delivery is an important issue, which should be taken into account in curcumin nano-formulation.
